Neuro 480 Final Exam
10. Explain the second messenger pathways generated by activation of phospholipase C
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11. Summarize the experiment shown in textbook figure 57-17.
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13. Discuss the ramifications of metabotropic receptors doing the following... • Activating or inhibiting phosphatases • Altering gene expression.
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2. Explain the phenomena of self-avoidance, tiling and coexistence during dendrite development. State the molecules that mediate each of these processes.
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2. Know that many mature neurons contain a single small neurotransmitter and one or more neuropeptides.
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3. The neurons in your cerebral cortex were originally formed in the ventricular zone during embryonic development. Explain how a neuron's "birthday" influences its layered position in the cortex. State how post-mitotic neurons migrate to their final positions in the cortex.
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5. Describe the action of neuregulin
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6. Describe the role that synapsin proteins serve in the storage and mobilization of synaptic vesicles
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Define the term "channelopathy". (See textbook page 170)
A disease caused by altered ion channels
Secondary active transport
Active transport that does not actively use ATP, but instead uses some other form of potential energy (such as a concentration gradient) to actively transport molecules
MAO
Monoamine oxidase; breaks down monoamines
Explain in molecular terms why no two neurons are exactly alike.
Expression patterns of ion channels differ, conferring different thresholds and firing patterns. Neurotransmitter and receptor expression patterns differ, conferring different transmission patterns at synapses.
13. Explain what is known about the structure of ligand-gated channels (ACh, GABA, Glycine channels). In you answer, include the number and names of subunits and the number of transmembrane regions in each subunit. (See figure 5-11A)
Five subunits; 2 alpha, one beta, one gamma, and one delta. Each subunit contains four transmembrane alpha-helices.
6. Explain how the structures of voltage-gated sodium channels and voltage-gated calcium channels are similar to and different than the structure of voltage-gated potassium channels. (See textbook pages 164-166 and figure 7-14)
Calcium and sodium have four repeated motifs in a single peptide. Potassium has four repeats of a subunit peptide. All three have 6 transmembrane domains per subunit/motif. But K is not a single peptide, its separated into 4 subunits
3 types of monoamines
Catecholamines, serotonin, and histamine
Briefly explain the spinal cord's circulation.
Cervical segments are fed by the vertebral artery. The rest is fed by branches off the aorta.
Explain the terms membrane resistance (Rm), axial resistance (Ra) and membrane capacitance (Cm). List the physical/molecular properties of a neurite that influence these values.
Membrane resistance: The resistance to flow of charge across the membrane. Should be high. Axial resistance: The resistance to flow of charge down the axon. Should be low. Membrane capacitance: The amount of charge on the membrane. Should be low.
6. Explain what pioneer neurons are and why they are important in development.
They are the first neurons to grow and synapse in the proper place. They are important because other axons grow on top of them in order to grow correctly
9. Explain how NMDA receptors act as a "coincidence detector". Explain how this allows for brain plasticity.
They need depolarization and glutamate and glycine binding, in order to activate. The calcium that enters from this coincidence, triggers second messenger systems that bring more NMDA receptors to the PSD and remove AMPA.
2. Summarize the experiments performed by Heuser and Reese that provide evidence for the vesicular release of neurotransmitter
That was supposed to be "ha"
types of catecholamines
dopamine, norepinephrin, epinephrine
1. Draw and briefly describe the structure of active zones at the neuromuscular junction. Include vesicles, calcium channels, and ACh receptors in your answer.
has
dopamine beta-hydroxylase
hydroxylates the beta carbon of dopamine to form norepinephrin
serotonin
made from tryptophan
Catecholamines
made from tyrosine
Explain how the anatomy of primary sensory neurons differs from typical neurons (like motor neurons). State where action potentials are initiated in primary sensory neurons. (see textbook figure 2-9)
Sensory neuron doesn't really have an axon hillock. The axon travels pretty much all the way from the end of the dendrite receive sensory information. It by passes the soma. Pseudounipolar.
10. Know that differential expression of Hox genes in discrete rostrocaudal domains of the hindbrain and spinal cord control the identity of motor neurons in the developing brainstem and spinal cord
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10. Know that neurotrophic factors activate receptor tyrosine kinases (Trks) and promote neuron survival by inhibiting apoptosis
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10. Name and describe the molecules that link pre- and post-synaptic cells together at CNS synapses.
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7. Contrast the location and function of laminins containing the 2 chain and laminins without the 2 chain in the development of the neuromuscular junction.
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7. Describe the experiments done by Viktor Hamburger that demonstrate regulation of neuron survival by signals from target cells.
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7. Explain the SNARE model of vesicle fusion. Include the roles of t-SNAREs (syntaxin and SNAP-25), v-SNARE (synaptobrevin/VAMP), Munc18, synaptotagmin, SNAP, and NSF
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7. Explain the signals involved in initial dendrite and axon guidance of pyramidal cells in the developing cortex
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Know that circumventricular organs do not have a blood-brain barrier. Know the names and functions of the circumventricular organs discussed in class.
Area postrema: vomiting Pineal, median eminance, neurohypophesis: Hormones Subfornical organ, subcommisural organ, organ vasculosum: electrolyte balance
Explain the basic differences between axosomatic and axodendritic synapses. (See textbook pages 230-232 and figure 10-16)
Axosomatic- Synapse directly on soma (no dendrites). Tend to be inhibitory Axodendritic- normal synapse on dendritic- usually excitatory (because spines have NMDA and AMPA)
11. Explain what a backpropagating action potential is (called an action potential echo in our literature papers).
Based on the types and number of channels present in the dendrites of those specific neurons.
9. Be able to draw and label the equivalent circuit diagram for a neuronal membrane under steady state conditions (Figure 6-11). Explain what batteries, resistors/conductors, current generators, and capacitors represent. (See textbook pages 135-138). Note: We will be using equivalent circuit diagrams quite often during the next few lectures. Spend extra effort to understand what resistors/conductors, capacitors and batteries are and how they act. Reading textbook appendix A may help.
Batteries=electric gradient, resistors=channels, current generators=, capacitors=plasma membrane.
21. Briefly state how local anesthetics such as novocain and lidocaine work to suppress pain.
Block Na channels to sequester the propagation of action potentials.
Describe how abnormal NMDA receptor activity is implicated in psychotic illnesses (such as schizophrenia) and in excitotoxicity following stroke or seizure.
Blocking NMDA receptors -> Hallucinations associated with schizophrenia (not enough glutamate)- antipsychotic meds are just NMDA agonists! Stroke/Seizure (too much glutamate)
COMT (catechol-o-methyltransferase)
Breaks down catecholamines
Describe the differences between Aa, Ab, Ad and C fibers. (See textbook pages 477-479 and textbook figure 22-2)
C is slow pain small diameter of neuron and no myelin Adelta is fast pain, myelinated, small diameter Abeta- touch/proprioception, mylenated, medium diameter, A alpha- proprioception, myelinated, large diameter.
5. List several potential effects of activating metabotropic glutamate receptors. Include short-term effects on membrane potential (EPSPs and IPSPs) and long-term effects.
Can be either excitatory or inhibitory, release intracellular calcium, open ion channels productions of endocannabinoids, activate kinases, transcription
9. Describe how anterograde and retrograde axonal transport are used by researchers to trace neuroanatomical pathways.
Can be injected with a tracer to see neuronal pathways. Antero- insert a labeled virus at the beginning of a circuit, and that then transfers to the 2nd and 3rd degree neurons. Retro - insert a labeled virus at the end of a circuit, and that virus then works backwards and show the 2nd and 1st degree neuron of the circuit.
12. List the causes and effects of demyelinating disease.
Causes: Destruction of myelin, defective myelin proteins. Effects: muscle weakness, lack of muscle control, tremors, convulsions, blindness, paresthesias (abnormal sensations).
4. Explain the concepts of silent synapses. How are silent synapses "woken up"?
Explain the concept of silent synapses. How are silent synapses "woken up"? (See textbook pages 1495-1497 and figure 67-5)
Explain what the "metabolic" blood-brain barrier is. Use transport of L-DOPA as an example.
L-DOPA enters brain endothelial via the L-system. Enzymes (namely monoamine oxidase) in endothelial cells rapidly metabolize L-DOPA which inhibits its entry into the brain (when giving L-DOPA pharmacologically, higher doses are often needed)
Describe the one-way flow of cerebrospinal fluid (CSF) through the CNS. Know how quickly CSF is replaced.
Lateral ventricle->third ventricle->cerebral aqueduct->fourth ventricle->subarachnoid space->out Adults have about 140 ml of CSF. 500 ml produced every day.
8. Summarize the four major regulatory mechanisms that control channel gating (see figure 5-6).
Ligand gating, phosphorylation gating, voltage gating, stretch or pressure gating.
4. Explain the functions of the following types of glial cells. (See pages 24-27) • Microglia • Oligodendrocytes • Schwann cells • Astrocytes
Microglia: Immune cells Oligodendrocytes: Meylination in the CNS Schwann Cells: Meylination in the PNS Astrocytes: not completely known, not essential to function, separate cells, regulate K+ levels, nourish surrounding neurons
2. Describe the molecular composition of microtubules in neurons and the term "dynamic instability".
Microtubules: Alpha and beta subunits form long chains (alpha-beta-alpha-beta etc.) called protofilaments. 13 protofilaments form a hollow tube 25 nm in diameter. Dynamic instability: Plus end of microtubule undergoes slow lengthening and rapid shortening.
We have learned that all parts of the neuron (axon, axon hillock, cell body and dendrites) contain voltage-gated channels. If this is the case, why are action potentials usually initiated at the axon hillock? (See textbook page 227 and figure 10-13)
More Na+ channels at hillock so more ability to start AP
Where are cholinergic neruons found?
Neuromuscular junction Autonomic nervous system
Compare and contrast the neuromuscular junction with CNS neuron-neuron synapses.
Neuromuscular junction: Input from one motor neuron, only excitatory input, one neurotransmitter, one receptor type, ~200 vesicles released, huge endplate potential always causes action potential in muscle. CNS synapse: input from hundreds or thousands of neurons, excitatory and inhibitory input, many neurotransmitters, many receptors for different neurotransmitters and the same transmitter, 1-2 vesicles released, small EPSPs-summation is required to reach threshold. CNS neurons have hundreds if not thousands of connections (neuromuscular only one) they receive both excitatory and inhibitory (neuromuscular only receives excitatory) responds to multiple neurotransmitters (neuromuscular only uses Acetylcholine) often many excitatory neurons must fire together to get an action potential on motor neuron (neuromuscular only requires 1 AP for one AP in muscle fiber)
too little dopamine (dopaminergic cells in the substantia nigra die)
Parkinson's
10. Explain how Ra , Cm , and Rm affect the speed of action potential conduction. Give examples of how these have been optimized in nature to increase the speed of action potentials.
Ra decreases (wider diameter), propagation increases Cm decreases (thick myelin), propagation increases Rm increase (less open channels), propagation increases
5. Injecting a step current pulse into a neuron changes the membrane potential in a predicable pattern (see the tracing below). Explain why the tracing is shaped the way it is (Why the slow, curved depolarization? Why the slow, curved repolarization after the pulse is removed?). How would increasing or decreasing membrane capacitance affect the shape of the voltage recording?
The capacitance of the membrane causes this sloping effect. steeper slope = lower capacitance Higher max = greater resistance... why? V=IR
2. Explain what a hydration sphere/shell is and how an ion's hydration sphere influences the flow of the ion through a channel.
The layer of water molecules surrounding and associated with an ion.
3. Neuronal membranes act like a resistor and capacitor in parallel (see the circuit in study objective #4). What physical characteristics/molecules account for the membrane acting like a capacitor? What physical characteristics/molecules account for the membrane acting like a resistor?
The nonconducting phospholipids separate charges (ions). This is the capacitor (infinite resistance). Ion channels have a finite resistance, and act as resistors.
2. Know that notch signaling regulates the production of neurons, astrocytes and oligodendrocytes in the cerebral cortex of mammals. (You do not need to know the details of how this occurs in mammals.)
dos
10. Be able to interpret tracings and graphs resulting from voltage clamp experiments (see figures 5, 11 and 12 in chapter 10 for examples).
easy. No current=reversal potential
Explain the basic differences between ionotropic receptors and metabotropic receptors.
ionotropic: ion channel pore (quick) metabotropic: G protein coupled receptors (slower, longer lasting)
Used in retrograde transmission
non-traditional neurotransmitters
1. Explain how the primary embryonic germ layers (ectoderm, mesoderm, and endoderm) form during gastrulation. Know that ectoderm gives rise to the epidermis and the major structures of the CNS and PNS.
one
1. Know the basic pattern by which synaptogenesis progresses at the neuromuscular junction
something here
2. Diagram a mature neuromuscular junction. Label and describe all important structures and cells
something there
Briefly explain how the stretch reflex is a good model for studying excitatory and inhibitory CNS synapses. (See textbook page 211and figure 10-1)
stimulus activates sensory neuron that goes to spinal cord which activates both an excitatory neuron (extensor) and an inhibitory interneuron (flexor)
Summarize the relationship between the three main brain fluid compartments: the interstitial, ventricular and vascular compartments.
there is no barrier between the interstitial fluid and CSF BBB between vascular and interstitial Blood-CSF barrier Each has three different fluids: Ventricular=CSF, Brain=Interstitial fluid, Vascular=Plasma. What would arachnoid space be? ventricular Yep, cause it is filled with CSF.
4. Explain what the membrane time constant (t, tau) is and how it's determined experimentally. State how a neurite's membrane resistance (Rm) and capacitance (Cm) affect its time constant. Know the typical values for a neuron's time constant.
time that it takes to get 63% of VMAX, Rm * Cm = tau, 20-50 msec is normal
2. Describe the anatomy of neurulation (see textbook figure 52-1). Include the terms ectoderm, neural plate, neural groove and neural tube in your answer
two
1. Explain how notch/delta signaling results in generation of neurons in Drosophila. Include the following molecules in your explanation: delta, notch, achaete-scute, suppressor of hairless, enhancer of split. (You need to know the details of this signaling pathway. See the 2nd slide on the handout and textbook figure 53-3)
uno
9. Define (both mathematically and in your own words) what λ, the length constant, represents. Memorize and be able to apply the following equations relating to the length constant:
λ=√(rm/ra). Lambda is the length constant. It tells us at what length the depolarization will be 63% lost. Distance that current can travel until only 37 percent of the charge is left. sqrt (Rm/Ra) = length constant delta Vx = delta Vo (e^(-distance/length constant))
8. Describe the downstream effects of cAMP and cGMP
• Direct binding and opening or closing of ion channels • Activation of cAMP- and cGMP-dependent protein kinases (know the basic structure of these kinases and how cyclic nucleotides regulate them).
Identify the following receptors as metabotropic, g-protein-coupled receptors:
• Muscarinic ACh receptors • Alpha- and beta-adrenergic receptors • GABAB receptor • Metabotropic glutamate receptors • Serotonin receptors • Dopamine receptors • Histamine receptors
Describe the functions of cerebrospinal fluid
buoy the brain, mechanical cushion, stabilize neuronal environment.
3. Briefly summarize the circuitry of the visual system
You can do this.
Dopa decarboxylase
Decarboxylates L-dopa to form dopamine
State the reversal potential for GABAA and glycine receptors (see textbook figure 10-11). Know that GABAA and glycine receptors are chloride channels.
-70 mV is Ecl so that's the money maker. Like Cl- is going into the cell
1. Briefly state how the number and density of synapses changes in the human brain during the first year of life, during childhood and during adulthood
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1. Explain how peptide neurotransmitters are synthesized, transported, stored, released from the axon terminal, and removed from the synaptic cleft
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1. Explain the consequences of axotomy (see textbook pages 1285-1287 and figure 57-1). Include a description of the following in your answer: • What occurs during Wallerian degeneration • What occurs during the chromatolytic reaction • Effects on downstream/postsynaptic neurons • Effects on upstream/presynaptic neurons (synaptic stripping, etc) • Effects on glial cells (oligodendrocytes, Schwann cells, reactive astrocytes, microglia)
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1. List the steps that occur as a neuron in culture grows an axon and dendrites (see textbook figure 54-1). Then, list the steps of dendrite development and maturation (see textbook figure 54-3).
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10. Describe how embryonic stem cells, induced pluripotent stem cells and adult stem cells could be used to treat Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS) and demyelinating diseases such as Multiple Sclerosis
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10. Explain how axo-axonic synapses modulate neurotransmitter release by presynaptic inhibition and presynaptic facilitation
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10. Explain how dorsal/ventral and rostral/caudal guidance of commissural interneurons occurs. Name the specific guidance molecules and receptors involved.
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12. Know that activation of Phospholipase A2 (PLA2) causes the release of arachidonic acid from the cell membrane. Know that arachinodic acid can then be converted into many different molecules that can directly or indirectly affect ion channels. Because these metabolites are lipid-soluble (can freely diffuse across membranes), they not only affect the cell in which they are generated, but neighboring cells as well. These metabolites are often used as retrograde messengers in the nervous system. Know that the most common metabolites of arachidonic acid are eicosanoids (prostaglandins, thromboxanes, leukotrienes).
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2. Know the specific points discussed on the third slide of the handout regarding rough patterning and refinement of synaptic connections
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3. Compare ACh receptor localization in muscle cells before and after synapse formation. Explain the three basic mechanisms that contribute to this change in localization
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3. Describe Hans Spemann and Hilde Mangold's experiment that led to the discovery of the organizer region
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3. Explain the idea of the "fusion pore".
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3. Name several neuroactive peptides. Know that many neuroactive peptides are hormones that are used in other body systems
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3. State Santiago Ramon y Cajal's contribution to developmental neuroscience
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4. Describe the synaptic vesicle cycle including neurotransmitter uptake, reserve pool, docking, priming, fusion, endocytosis and recycling
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4. Explain how small neurotransmitters are classified into families.
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4. Explain how the neural plate forms (termed primary neural induction). Include the roles of the organizer region and the following molecules: BMP, chordin, noggin and follistatin
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4. Explain the roles that agrin, MuSK, Lrp4 and rapsyn play in ACh receptor relocalization. Summarize the experiments that led to the discovery of agrin
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4. Several experiments involving refinement of connections in the visual system are discussed in chapter 56. For each of the following figures, explain the experiment that was performed, the results that were obtained, and the conclusions that were drawn. • Figure 56-3 (see also textbook pages 1262-1263) • Figure 56-4 (see also textbook pages 1263) • Figure 56-5 (see also textbook pages 1263) • Figure 56-6 (see also textbook pages 1263) • Figure 56-7 (see also textbook page 1264-1266) • Figure 56-8 (see also textbook pages 1266-1267) • Figure 56-11 (see also textbook pages 1269-1270) • Figure 56-12 (see also textbook pages 1270-1271)
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4. Where do neural crest cells originate? What cell types do neural crest cells become during development?
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5. Explain each of the following mechanisms by which cycling of vesicles may occur. • Full exocytosis followed by classic clathrin-mediated endocytosis • Reversible fusion pore (kiss-and-run)
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5. Explain how Wnt signaling influences the rostrocaudal pattern of the neural plate
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5. Explain the mechanism by which small neurotransmitters are packaged into vesicles. Name the vesicular transporters that package monoamines, ACh, GABA and glutamate into vesicles.
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5. Know that the barn owl uses visual cues to hunt during the day. The owl uses auditory cues to hunt at night (using interaural time differences). These two sets of inputs converge on the tectum (superior colliculus), resulting in the formation of visual and auditory maps that drive head and flying movements toward their prey during hunting.
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5. List and describe the six different types of guidance cues that growth cones respond to during pathfinding (see figure 54-9). Know common molecules that mediate each of these processes and where these molecules are found (extracellular matrix, soluble gradient in brain tissue, or attached to cell membranes)
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5. Summarize experiments demonstrating the inhibitory aspects of CNS myelin
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5. The fate of individual neural crest cells is influenced by the environment through which the cell migrates. In particular, secreted factors from neighboring cells influence the differentiation of neural crest cells. List the specific cell types produced when the following molecules act upon neural crest cells: BMP, GGF, TGF-beta, Wnt.
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6. Explain how the midbrain and hindbrain are patterned. Include the roles of the isthmic organizer at the midbrain-hindbrain boundary, secreted molecules (FGF and Shh), and transcription factors (Otx2 and Gbx2). What causes the production of dopaminergic neurons and serotonergic neurons?
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6. Explain the mechanism by which small neurotransmitters are removed from the synaptic cleft back into the axon terminal (reuptake). Name the transporters that reuptake monoamines, ACh, GABA and glutamate.
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6. Give an example of how signals from target cells influence the neurotransmitter phenotype of the innervating neuron
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6. Name the inhibitory molecules found in oligodendrocytes myelin and astrocytic glial scars
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6. Several experiments involving plasticity of the barn owl auditory map are discussed in chapter 56. For each of the following figures, explain the experiment that was performed, the results that were obtained, and the conclusions that were drawn. • Figure 56-17 (also see textbook pages 1276-1277) • Figure 56-20 (see also textbook pages 1278-1280)
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6. Summarize how differences in muscle electrical activity affect production of ACh receptors in mature muscle
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7. After closure of the neural tube in early embryos, molecules named sonic hedgehog (Shh) and bone morphogenetic protein (BMP) are involved in dorsal-ventral patterning of the nervous system. Explain where each of these molecules is expressed. Then, explain how gradients of these two molecules result in the mature dorsal-ventral pattern found in the spinal cord (list the basic cell types they induce the formation of)
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7. For each of the neurotransmitters listed below... (A) Explain how the transmitter is synthesized (intermediates, synthetic enzymes). (B) List and describe the transmitter's receptors. (C) Explain how each transmitter is removed from the synaptic cleft. If applicable, name the enzyme(s) responsible for enzymatic breakdown of the transmitter. (D) Discuss important physiological and clinical considerations relating to the neurotransmitter Neurotransmitters... • Acetylcholine • Dopamine • Norepinephrine • Epinephrine • Serotonin • Glutamate • GABA
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7. Summarize "conditioning lesion" experiments that provide evidence for an intrinsic growth program promoting regeneration (see textbook pages 1294-1295 and figure 57-9). Know the molecules involved in the intrinsic grown program.
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7. Summarize the data shown in textbook figure 56-1 relating to social development.
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8. After reviewing the chapter, summarize the concept of "critical periods" during development of the CNS.
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8. Explain how formation of new connections by intact axons can lead to functional recovery
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8. Explain reasons why synapse formation is more complex in the CNS than it is at the neuromuscular junction.
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8. Explain the effects tetanus and botulism toxins have on the nervous system. Explain the molecular mechanism by which each acts
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8. Explain the molecular guidance process that determines whether a retinal ganglion cell axon crosses or doesn't cross at the optic chiasm during axon pathfinding
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8. Explain the molecular mechanism by which sonic hedgehog changes gene expression in target cells. Include the roles of Shh, patched, smoothened, Gli (sometimes called Ci), transcriptional activators, transcriptional repressors and Shh target genes
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8. Explain the neurotrophic factor hypothesis
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9. Below is a very basic outline of the important events that occur as the neural tube develops into the brain and spinal cord. Know the events and be able to identify each structure or region on a diagram like figure 52-2. • The prosencephalon (forebrain) divides, forming the telencephalon and diencephalon. The telencephalon then develops to form the cerebral hemispheres. The diencephalon develops to form the thalamus, hypothalamus, and retina. • The mesencephalon (midbrain) develops into the midbrain. • The rhombencephalon (hindbrain) divides, forming the metencephalon and myelencephalon. The metencephalon develops into the pons and cerebellum. The myelencephalon develops into the medulla. • The caudal neural tube becomes the spinal cord. • The fluid filled center of the neural tube becomes the brain ventricles and the central canal of the spinal cord.
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9. Explain how different neurotransmitter receptors are clustered at synapses in the CNS. (i.e. What molecule induces glycine receptors vs. glutamate receptors to cluster at a synapse?)
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9. Explain the molecular guidance processes that guide posterior retinal ganglion cell axons to synapse in the anterior optic tectum and anterior retinal ganglion cell axons to synapse in the posterior optic tectum.
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9. Explain why tetanic stimulation can lead to potentiation of transmitter release. Then, explain why prolonged tetanic stimulation can cause synaptic depression
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9. Name two places where neurons are born in the adult rodent. State where the new neurons migrate to and state the type of neurons the new neurons become.
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9. Understand that different neuronal subtypes depend on different neurotrophic factors for survival (see textbook figure 53-15 for a few examples; you do not need to memorize which specific factors are required by which subtype of neuron).
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Briefly state the mechanisms by which receptor tyrosine kinases influence neurons. What ligands bind to and activate these receptor tyrosine kinases?
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Compare and contrast the physiological actions of ionotropic and metabotropic receptors. Give several examples of how metabotropic receptors modulate neuron activity.
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Describe the basic structure of G-protein coupled receptors.
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Explain how activation of G-proteins can lead to the formation or destruction of cAMP and cGMP. Include the effects of alpha-s and alpha-i subunits on adenylyl cyclase and the effect of other alpha subunits on phosphodiesterases.
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Explain how blood is returned from the scalp, skull, and brain to the heart.
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Explain how gaseous neurotransmitters (NO and CO) alter levels of cGMP
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Explain the basic mode of operation for all G-proteins
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Explain what anastamoses are and discuss their significance/function. Give an example.
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Know that beta/gamma subunits can directly bind to and open or close ion channels. Alpha subunits can activate or inhibit several effector proteins
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Know the statistics regarding brain circulation and blood flow presented on the first presentation slide (Appendix C)
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Name and be able to label the arteries that blood passes through as it ascends up the neck and enters the cranium
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Summarize the various ways a rise in intracellular calcium levels can lead to modulation of ion channel function.
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summarize the important role of growth/trophic factors in axon regeneration
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Indicate the molecular composition of GABAA and glycine receptors. Include the number of subunits per receptor and the number of transmembrane regions per subunit. (See textbook figure 10-7 and page 226).
5 subunits, 4 transmembrane domains per subunit, not all subunits are the same Same family as Ach receptors Different subunits confer different properties
1. What is a capacitor? What is a resistor? How does each act when placed in a circuit with a battery and the circuit is closed or opened? (See the first several slides of Dr. Sudweeks' handout)
A capacitor (originally known as a condenser) is a passive two-terminal electrical component used to store electrical energy temporarily in an electric field. It is the cell membrane. A resistor is a passive two-terminal electrical component that implements electrical resistance as a circuit element. Resistors act to reduce current flow, and, at the same time, act to lower voltage levels within circuits. (channel?) Capacitor is filled first, then resistor gets some love. Then when circuits closes, the capacitor then discharges everything (current going in the opp. direction now)
Describe what happens in a dendritic spine when it simultaneously is exposed to an EPSP (neurotransmitter) and a backpropagating action potential. (See textbook page 231and figure 10-18)
A much larger influx of Ca is created, more than what would normally be expected through summation of the two. Ca can then be used as a second messenger to perform various jobs throughout the cell.
5. Be able to interpret current tracings such as those seen in textbook figures 5-2 and 5-3. Explain how the voltage/current graph in figure 5-2C was generated from the data in figure 5-2B.
Again, downward tracing is positive ions flowing in and upward is positive leave the cell. They basically just did whatever the membrane potential was on the x axis and the height of the box (current) on the y-axis.
Describe the effect of GluA2 subunits on calcium permeability of AMPA receptors (see textbook pages 219-220 and figure 10-9).
AMPA mRNA translated to protein WOULD let Ca+ through. But there is Post translational editing changes a Gluta mine to a Arginine in one of the 4 subunits (M2) NMDA - contains asparagine (N) (neutral) AMPA - contains glutamine (Q) (neutral) but GluA2 subunit undergoes editing to make arginine (R) (charged) so it doesn't let Ca through If AMPA didn't have a GluA2 subunit, it could be permeable to Ca
Types of small neurotransmitters (5)
Acetylcholine, biogenic amines, amino acids, purines, and non-traditional
List known agonists and antagonists of NMDA glutamate receptors. Explain the special properties of the NMDA receptor that make it different than non-NMDA ionotropic glutamate receptors. Include the following in your discussion: glycine, Mg+2, voltage-dependence, calcium, second messenger systems (such as PKC and CamKII)???
Agonists: Glu, Glycine, exogenous NMDA Antagonists: Mg2+ (blocks pore), MK801, APV, PCP, Zn2+ (MAPZ is an acronym) NMDA - allows Ca2+ ions through. Opens slower than AMPA, but allows more current through. Has Tons of other regulating molecules. Glycine is a required co-agonist.. Has a Mg2+ plug in the channel, which is only unplugged above -40mV. The increase in Calcium++ through NMDA in the postsynaptic cell then turns on second messenger systems such as PKC and CAMKII
7. List known agonists and antagonists of NMDA glutamate receptors
Agonists: NMDA and glycine. Antagonists: MK801, PCP, APV, zinc and magnesium.
5. Reconcile data obtained from patch clamp analysis of single nicotinic ACh channels with the whole-cell current tracings of the end-plate potential (see textbook figures 9-10 and 9-11).
All Ach channels will open almost simultaneously in response to a stimulus but close independently to one another. In vivo, there are thousands of channels so it is difficult to resolve the effect of each channel. Because there are so many channels, the curve tends to be smoothed out. Summary- ACH RECEPTORS Open together, don't close together
Explain how the following drugs affect GABAA receptors: benzodiazepines (valium, librium), barbiturates (Phenobarbital), ethanol. (See textbook page 226)
All increase Cl- current All have different binding sites, all inhibitory EVEN if below Ecl, b/c "clamps RMP near Ecl"
6. Diagram and explain the equivalent circuit diagram of a neuronal axon or dendrite (slides #19 and 20 in Dr. Sudweeks' handout).
Alot of this is explained in #5 (orientation of batteries). Unexplained: When + ions enter the cell, they will travel down the path of least resistance, which is going to charge the capacitor. This means that when + ions enter, they will first go to neutralize the (-) charge on the inside leaflet of the membrane.
Describe the basic structure of G-protein coupled receptors.
Alpha, beta, gamma units ligand binds the receptor and the subunits clap and yell "Break!" and do their thing. 7 transmembrane subunits
What are the main "work horse" neurotransmitters of the nervous system?
Amino acids
Explain what an end-plate potential is and why curare must be used when experimentally studying end-plate potentials.
An end plate potential is basically just an EPSP. Release of Acetylcholine opens up Ach receptors in the muscle membrane end plate which depolarizes the cell. This causes an EPSP or end plate potential. curare is necessary because it blocks the binding of Ach to a receptor which does not allow an action potential to occur. this way, currents that contribute to an end-plate potential (which are different than those that create an action potential) can be studied Curare prevents the end plate potential from reaching threshold
How would the following conditions affect the above voltage tracing (see question 9)?
An increase or decrease in membrane capacitance (Cm)- ex. INCREASE Cm - increases time to get to VMAX , Same VMAX · An increase or decrease in membrane resistance (Rm) ex. INCREASE Rm, increase the VMAX. Does take more time to get to 63% full??? Yes siree! · An increase or decrease in the amount of current injected ex. INCREASE I- increase VMAX, but time that it takes to get 63% of VMAX is unchanged.
Explain the differences between cell-attached, inside-out, whole-cell and outside-out varieties of patch clamp.
Cell Attached - pipetted touches plasma membrane and suctioned slightly to create seal (cell still controls channel) Inside out - If previous patch removes channel from membrane, it becomes inside out (you control membrane potential) how channel works (now we have control over channel) Whole cell - begins same as first but suction so hard that channel is broken so the cytoplasm normalizes to fluid inside pipette (observe multiple channels) Outside out - if you slowly remove the pipette from the whole cell patch, you will get one channel (hopefully) and some lipid membrane (measure single channel) current
Explain the basic differences between ion channels and ion pumps (see figure 5-19).
Channels have a continuous pathway for ion conduction. Pumps have two gates in series that control ion flux. Both gates are never open at the same time.
9. Define and explain the following terms relating to neuronal input: chemoreceptor, mechanoreceptor, photoreceptor, thermoreceptor, receptor potential, synaptic potential, IPSP, EPSP, transduction, transmission, transmitter-gated ion channels, G-protein-linked ion channels.
Chemoreceptor: A sensory neuron that transduces a chemical signal into an electrical impulse. Found in the nose and tongue. Mechanoreceptor: A sensory neuron that transduces a mechanical signal into an electrical impulse. Found in skin and muscles. Photoreceptor: A sensory neuron that transduces light energy into an electrical impulse. Found in the retina of the eye. Thermoreceptor: A sensory neuron that transduces a temperature signal into an electrical impulse. Found in the skin. Receptor potential: The membrane potential of a sensory receptor. Synaptic potential: The change in membrane potential after a synaptic event. IPSP: Inhibitory Post-Synaptic Potential EPSP: Excitatory Post-Synaptic Potential Transduction: Transforming energy from one form to another, such as light in the retina to an electric impulse. Transmission: Propagating a message from one neuron to another
Explain how a whole-cell voltage clamp experiment (textbook figure 9-7) can be used to generate an IV plot.
Clamp the cell at various voltages, and measure the current that results. I(Na)=g(Na) x (Vm-E(Na)) plot..
6. Be able to interpret IV plots. Explain the terms reversal potential and conductance. Given an IV plot for a channel, be able to determine the reversal potential and calculate the conductance of the channel.
Conductance is the slope. V is x axis, Y axis is current Conductance is the slope. (use base units when calculating slope. Units: I/V = S) Reversal potential is where the line crosses the x axis.
7. Summarize the three general models of channel gating (see figure 5-5).
Conformational change, general structure change, blocking particle.
5. List several types of actin-binding proteins.
Cross linking proteins: Link filaments together Severing proteins: Sever the growing end Capping Proteins: Cap the growing end Motor proteins: Axonal transport
1. Review the basic anatomy of a neuron. Explain the concepts of dynamic polarization and connectional specificity. (See pages 22-24)
Dendrite-typically receives input signal, spines Soma-Cell body, summarizes (processes) signal Axon-propagates signal, composed of axon hillock (initiates action potential), axon, meilin, and axon terminal (releases neurotransmitter to send signal to next cell)
Define the term "channelopathy". (See textbook page 170)
Diseases caused by altered ion channels. ex. disorder slows the rate of Na inactivation. Slower repolarization.
6. Explain the difference between divergent and convergent circuits in the CNS.
Divergent means that one neuron activates many target cells. Convergent means that many inputs reach the same target cell.
Explain why GABAA responses during development are excitatory and how they change to inhibitory responses during maturation. (See textbook page 225)
Ecl is different in infants!!! Cl- concentration changes as you age. As a baby, your cells sequester Cl- inside, so their ECl is probably like -30 mV, and Cl- leaves when the channel is open. But as adults, the most of [Cl-] is outside the cell. In an immature neuron the reversal potential for a GABA receptor is way above threshold and opening GABA depolarizes the cell. Later, when we mature, a Cl pump is produced to kick Cl- out of the cell. This causes the same GABA receptor to become a hyperpolarizing cell because of the change of Cl concentration.
8. Summarize important principles applying to neuronal input (as discussed in class).
Electrical properties: Input - local change in membrane potential Graded (amplitude and duration is variable) Degrades with distance (spreads passively) Degrades with time Either Depolarizing/hyperpolarizing Two sources of inputs is info Received from a sensory receptor or another neuron (synaptic). Input from sensory receptors: results in "receptor potentials" photoreceptor: rods and cones From other neurons: "synaptic potentials" mechanoreceptors - knee jerk reflex - hitting knee which sends impulses Input from other neurons
10. Explain how the following molecules affect ligand-gated ion channels: endogenous ligands, reversible antagonists, irreversible antagonists, and exogenous regulators. State specifically how curare and alpha-bugarotoxin affect ACh receptors/channels. (See figure 5-8)
Endogenous ligand: The ligand that typically binds to a channel (such as dopamine or ACh) Reversible antagonists: antagonists that can come off (Antagoinists bind to the ligand binding site, but do not cause the nessecarry conformational change to open the channel.) Irreversible antagonists: antagonists that do not come off. Exogenous regulators: factors that bind to a distant site to regulate channel activity. Curare is an ACh reversible antagonist. Alpha-bugarotoxin is an ACh irreversible antagonist.
Vesicular transporter
Exchanges H+ for neurotransmitter in the vesicle
8. For each of the following types of axonal transport, note the direction and molecular mechanism of movement, what is transported, and the speed of transport. • Fast anterograde transport • Slow anterograde transport • Fast retrograde transport
Fast anterograde: kinesin on microtubules, organelles, 400 mm/day or faster. Slow anterograde: ?, cytoskeletal and metabolic proteins, 0.2-5 mm/day. Fast reterograde: MAP-1C on microtubules; organelles and vesicles, growth factors from post synaptic cell, toxins and viruses; 200-300 mm/day.
7. Diagram and explain the difference between feed-forward and feed-back inhibition.
Feed-forward: Feed-back: A neuron has excitatory synapses with an inhibitory interneuron that in turn inhibits the first neuron.
9. Describe the subunit composition of the nicotinic ACh receptor that is found at the motor end-plate. Name the 5 subunits. How many ACh molecules must bind to the channel to open it? (See textbook figure 9-13)
Five subunits; 2 alpha, one beta, one gamma, and one delta. Each subunit contains four transmembrane alpha-helices. 2 ACh must bind. They bind to each alpha subunit. composed of 5 subunits 2 alpha, beta, delta, and gamma 2 Ach necessary to bind to extracellular binding sites to open pore to Na and K (binding site found between alpha and gamma / alpha and delta interfaces)
Explain the acronyms EPSP, EPSC, IPSP and IPSC
For currents in and out of cells in general... IT'S POSITIVE TO LET THE CAT OUT. soooo.... cations leaving the cell is a positive current. negative leaving is negative. negative coming in is positive. positive coming in is negative. credit to Dr. Woodbury from advanced phys lab. Excitatory postsynaptic potential (EPSP) On a voltage graph, it goes up (depolarization) Excitatory Postsynaptic current (EPSC) On a current graph, it goes down (inward current) Inhibitory Postsynaptic potential (IPSP) On a voltage graph, it goes down. (hyperpolarization) Inhibitory Postsynaptic current (IPSC) On a current graph, it goes up (outward current)
Briefly state the mechanisms by which receptor tyrosine kinases influence neurons. What ligands bind to and activate these receptor tyrosine kinases?
Forms dimer, phosphorylate each other, then start phospho'ing other proteins. neuroplasticity, cell survival, neuronal differentiation and growth. Activated by growth factors, neuropeptides, hormones (not just neurotransmitters) GROWTH FACTOR IS A LIGAND
14. Explain what is known about the structure of gap junction channels. In your answer, include the number of subunits required to make a functional gap junction and the number of transmembrane regions in each subunit. (See figure 5-11B)
Gap junction channels are formed by a pair of hemichannels, one each in the presynaptic and postsynaptic membranes. Each hemichannel is made of six identical subunits each containing four transmembrane regions.
5. Explain how the resting membrane potential is generated and maintained in glial cells and in neurons. Be sure to explain the roles of individual ion species, ion channels, ion pumps, and ionic chemical and electrical driving forces. (See textbook pages 127-134)
Glial cells: Resting membrane potential -80 mV Permeable to K+ only Outside of the membrane accumulates a positive charge with flow of K+ outside of the membrane. Once K+ diffusion has proceeded to a certain point, the electrical driving force of K+ exactly balances the chemical driving force. = "equilibrium potential" Since glial cells are only permeable to potassium, the equilibrium potential of K+ (Ek) is equal to the resting membrane potential. Neurons: Resting membrane potential -64.1 mV Permeable to Na+, Cl-, and K+. Na+ is driven into the cell by chemical and electrical gradient. The membrane potential doesn't come close to Na+ equilibrium potential (+55 mV). Why? Many more K+ channels. Membrane potential reaches a new resting level where increased outward movement of K+ balances the inward movement of Na+. Ion flux = (electrical+ chemical driving force) X membrane conductance For Na, a is high but b is low For K, a is low but b is high
Explain the properties of the following BBB transport pathways • The Glut1 system • The L system • The A system • Active ion exchangers (i.e. Na+/K+ ATPase)
Glut1: Facilitated diffusion of Glucose in and out of the brain L system: Facilitated diffusion of leucine and L-dopa A system: Secondary active transport of sodium and Glycine out Na+/K+ ATPase: 2 sodium in, 3 potassium out
6. Indicate the molecular composition of each of the following ionotropic receptor families. Include the number of subunits per receptor and the number of transmembrane regions per subunit. (See textbook figure 10-7). • Glutamate receptors (AMPA, Kainate, NMDA) • ACh, GABAA, and glycine receptors
Glutamate receptors have four subunits with three transmembrane regions and one that's like half transmembrane. Everything else has five subunits; 2 alpha, one beta, one gamma, and one delta. Each subunit contains four transmembrane alpha-helices.
Know that glutamate is the primary excitatory neurotransmitter in the CNS. State the basic differences between AMPA, Kainate, NMDA and metabotropic glutamate receptors.
Glutamate: used for fast signaling (sensory, sensations, activate spinal cord) How is each receptor unique: AMPA/Kainate - only regulated by Glutamate NMDA - allows Ca2+ ions through. Opens slower than AMPA, but allows more current through. Has Tons of other regulating molecules. Glycine is a required co-agonist There's so much glycine in the CSF that it's not really a factor (already in CSF, don't need additional).. Has a Mg2+ plug in the channel, which is only unplugged above -40mV, so you need spatial summation or back-propogating AP to effectively fire the NMDA receptor mGlu - can be either EPSP or IPSP, depending on which 2nd messenger path it sets off
4. Describe the structure and function of growth cones
Growth cones are the ends of developing axons. They get the axon where it needs to go, and form the proper synapses. They are a lot like dendritic spines in terms of structure.
Describe the voltage clamp experiments performed by Hodgkin and Huxley that demonstrated the ionic basis of the action potential. Be able to diagram, label and explain a current tracing and a voltage tracing recorded during an action potential. Also be able to draw and explain how TTX and TEA affect such current and voltage tracings. (See the first several slides of the handout. Also review textbook figures 7-3 and 7-10)
History: Eliminating Sodium from the solution took away the inward current. ~TTX The initial inward current (negative) is from the Sodium channel opening. Then the outward current (positive) comes later from the slower Potassium channel, once the Sodium channel has closed. TTX blocks Sodium, so you don't have any inward current. Just the rising outward current. TEA blocks Potassium channels, so you ONLY have the inward current.
11. Ion channels may be composed of several subunits. Explain the difference between heterooligomers, homooligomers, and repeated motifs. Some ion channels may also have auxiliary subunits—state the function of such subunits. (See figure 5-9)
Homooligomers: Channels constructed from subunits of a single type. Heterooligomers: Channels constructed from different types of subunits. Repeated motifs: Channel "subunits" are all connected in a single polypeptide chain. Auxiliary subunits: Subunits that are not involved in forming the ion pore core. (Think G-proteins.)
Tyrosine hydroxylase
Hydroxylates Tyrosine to form L-dopa
7. A typical action potential can be explained solely using the characteristics and behaviors of the voltage-gated Na+ channel (INat) and K+ channel (IK). In reality, there are dozens of other types of voltage-gated ion channels. The presence of these ion channels changes the electrical activity of neurons in significant ways. Describe the characteristics of the following voltage-gated currents. Explain how each influences the excitability of neurons. • INat • INap • IL • IT • Ih • IK • IC • IA • IM
INat: Transient sodium current. Transient, rapidly acivating and inactivating. Found in the axon. Typical action potential current. Inap: Persistent sodium current. nonactivating. soma and dendrites. enhances depolarization. contributes to steady state firing. Il: long-lasting calcium current. slowly inactivating. dendrites and axon terminal. dendritic calcium spikes and synaptic transmition. It: Transient calcium current. dendrites. Quick depolarization of dendrites. underlies rhythmic burst firing. Ih: Inward cation current. Activated by hyperpolarization below -70. soma and dendrites. creates unstable resting potential. contributes to rhythmic burst firing. Ik: Normal potassium current. slowly activated by depolarization. axon. repolarization of action potentials. Ic: potassium current activated by depolarization, requires increase in internal ca. soma and dendrites. increases interspike interval. Ia: transient inactivating potassium current. soma and dendrites. delays onset of firing , lengthens interspike interval. Im: slowly activated potassium current, blocked by muscarinic ACh receptors. soma and dendrites. contrubutes to spike frequency adaptation. blocking this current increases neuronal excitability.
8. Describe how an increase or decrease in Rm , Ra , or Cm affects the passive spread of current down a neurite.
If Rm is higher than Ra, the charges will just flow right back out instead of spreading down the axon. If Cm is high, more charges will be required to neutralize the membrane potential, so less will be left to spread.
9. Why is understanding the concept of critical periods important in the fields of medicine, psychology and education?
If we know when the critical periods are, we can use treatments more effectively and teach things at the right time.
8. Our book states that resting neurons are not in equilibrium but rather in a steady state (see page 131, right column). Explain what this means. How is steady state different than equilibrium?
In equilibrium, the influx of positive ions exactly equals the efflux of positive ions. This is true. Influx of sodium equals the efflux of potssium. However, if this were allowed to continue unopposed, the concentration gradients would run down, eventually neutralizing the membrane potential. Instead, there is a continuous passive influx and efflux through the membrane that is exactly countebalanced by active ion exchange in the sodium potassium pump.
Explain where and how CSF is drained into the venous system
In the arachnoid villi, CSF is taken up by endocytosis and exocytosed into the blood stream
5. Explain how the basic voltage-gated potassium channel has been modified to produce inactivating K+ channels, depolarization- and calcium-dependent K+ channels, and cyclic nucleotide-dependent cation channels. (See textbook pages 167-170 and figure 7-17).
Inactivating: Added a ball to the N- terminus, cytoplasm. Dep and Calc: Add a Ca2+ binding site to the C-terminus, cytoplasm side. Cyc Nuc-dep: Add a cyclic nucleotide binding site (cAMP??) to the C-terminus, cytoplasm side.
Describe how an increase or decrease in Rm , Ra , or Cm affects the passive spread of current down a neurite.
Increase in Rm- FASTER, you don't want ions leaky out of the pipe. Increase Ra- SLOWER Increase Cm- SLOWER
7. Describe how the following would affect membrane potential. Explain your answers. • Increased or decreased sodium permeability • Increased or decreased potassium permeability • Increased or decreased chloride permeability • Hypernatremia (high extracellular Na+ conc.) or hyponatremia (low extracellular Na+ conc.) • Hyperkalemia (high extracellular K+ conc.) or hypokalemia (low extracellular K+ conc.)
Increased or decreased sodium permeability increase=greater depolarization · Increased or decreased potassium permeability increase= greater hyperpolarization · Increased or decreased chloride permeability increase= greater hyperpolarization · Hypernatremia (high extracellular Na+ conc.) or hyponatremia (low extracellular Na+ conc.) hypernatremia= More Na wants to flow in, greater depolarization · Hyperkalemia (high extracellular K+ conc.) or hypokalemia (low extracellular K+ conc.) hyperkalemia= less K wants to flow out, smaller hyperpolarization
10. Summarize important principles applying to neuronal integration (as discussed in class).
Integration of different signals that converge on the trigger zone/axon hillock... where action potential starts. There are tons of voltage gated Sodium channels at the hillock, hoping to "get this partay started!"
11. Summarize important principles applying to action potential conduction and neuronal output (as discussed in class).
Integration site - highest density of voltage-gated Na+ channels. Where summation occurs (of graded potential) Action potentials: Initiated at trigger zone when threshold is reached Stereotypical event lasting 1-2 milliseconds. Mediated by voltage-gated channels All-or-none self-propagating/regenerative Propagation velocity is variable... up to 120 meters/second NT is released... Amino acids, Amines, peptides Amount of secretion dictated by frequency of action potentials arriving at axon terminal. Affects membrane potential of the postsynaptic neuron
Compare and contrast the physiological actions of ionotropic and metabotropic receptors. Give several examples of how metabotropic receptors modulate neuron activity. (See the first five slides of the handout and textbook pages 250-253).
Iono- fast acting, just a pore, neurotransmitter causes opening of channel, modify EPSP and IPSP, work horses of the nervous system Metab- slow acting long lasting (protein changes that last), NT can open channel, may modulate many neuronal functions, 2nd messenger can diffuse through the cell, affects distant regions
4. Explain the basic differences between ionotropic receptors and metabotropic receptors.
Ionotropic receptors are ion channels. They cause a rapid change in membrane potential. Metabotropic receptors activate second messenger systems. They cause a slower, longer lasting change in membrane potential.
For each of the following ionotropic receptors, indicate A) The endogenous ligand (neurotransmitter) that activates the channel B) Which ions pass through the channel C) Whether activation of the receptor causes an EPSP or IPSP.
Ionotropic receptors: · NMDA receptors Glutamate (co with Glycine) / Na, K, and Ca / EPSP · AMPA receptors Glutamate / Na,K (Can be Ca as well if GluA2 isn't there) / EPSP · Kainate receptors Glutamate / Na,K / EPSP · GABAA receptors- GABA / Cl- / IPSP · Glycine receptors Glycine / Cl- / IPSP · Nicotinic ACh receptor ACh / Na, K / EPSP · 5-HT3 receptors Serotonin Serotonin / Na, K / EPSP
10. Diagram and describe the molecular structure of a single subunit in the nicotinic ACh receptor and how the 5 protein subunits are arranged to form the ion channel pore. What molecular properties of the M2 transmembrane helix is thought to contribute to the channel's specificity? (See textbook figure 9-14).
M1-M4 in each subunit (5 subunits total). M2 lines the inner layer of the pore and has a lot of negatively charged amino acids to attract positively charged ions that flow through the channel (serine and threonine residues form selectivity filter)
3. Explain the roles that microtubule capping proteins and microtubule associated proteins (MAPs) have in neurons. Know the names of MAPs that are found in dendrites and axons.
MAPs are microtubule associated proteins. Microtubule capping proteins, which cap the + end, allow lengthening, and prevent disassembly of microtubules. The purpose of MAPs are to link microtubules together and stabilize neurites. MAP-2: dendrites MAP-3: axon Tau: axon
Explain the function of the blood-brain barrier (BBB).
Maintain stable environment for neurons by excluding toxins, wastes and neuroactive substances while providing glucose and other essential nutrients.
4. Explain the patch clamp technique and how single channel recordings can be used to generate an IV plot (see textbook figures 9-8 and 9-9)
Many different kinds of patch clamp techniques as we have learned. It is a good way to study the properties of a cell channel or multiple channels. Again they plot current vs membrane potential. They found that Ach channels behave similar to resistors and are ohmic channels (constant slope). Control the voltage for one channel. The certain voltage will result in a different amplitudes of current. The greater difference between Vm and Ea, the greater the amplitude going through that channel. The reversal potential is when no current passes through.
1. Describe the location of microfilaments, microtubules, and intermediate filaments in neurons. Know that cytoskeletal proteins make up 25% of all neuronal protein.
Microfilaments: 1. Immediately beneath membranes 2. At tips of growing neurites 3. In axon terminals 4. In dendritic spines 5. In very dynamic areas Microtubules: 1. Run longitudinally in neurite shaft 2. Radiate from MTOC in soma 3. In relatively stable areas Intermediate filaments: 1. Throughout soma 2. In healthy mature neurites 3. Give strength and inhibit dynamics
4. Describe the molecular composition of microfilaments in neurons and explain the process of "treadmilling".
Microfillaments: Polymer of actin monomers wound in a thin double-stranded helix. Monomers add to plus end and leave from minus end. Treadmilling: Actin filaments are constantly adding and removing monomers on each end. This leads to a very dynamic structure.
Explain how the lipid-solubility of molecules influences their ability to cross the blood-brain barrier. Know the relative lipid-solubility and BBB-crossing ability of the molecules in textbook figure D-6. Explain why some lipid-soluble substances cannot cross the BBB and why some lipid-insoluble molecules cross the BBB very efficiently.
More lipid soluble=more ability to cross BBB. Nicotine, ethanol, Diazepam (vallium), heroin chloramphenicol(?): High lipid solubility, High relative extraction (near 100%) Methotrexate, mannitol, dopamine, morphine, sodium, penicillin: low lipid solubility, low relative extraction (near 1%) Oddballs: Water, Glucose and L-dopa have fairly High extraction rates, but are not very lipid soluble. Phenobarbitol and Phenytoin are lipid soluble, but don't make it across as much as the others (size)
8. Explain the special properties of the NMDA receptor that make it different than non-NMDA glutamate receptors. Include the following in your discussion: glycine, Mg+2, voltage-dependence, calcium, second messenger systems (such as CamKII).
NMDA receptors need glycine and glutamate to work. Also, magnesium sits in the pore and requires depolarization to be bumped out. It is a calcium channel in addition to the sodium and potassium, which causes second messenger cascades.
Explain how NMDA receptors act as a "coincidence detector" (co-incidence meaning two-occurrences at the same time and space). Explain how this allows for brain plasticity.
NMDA works only when PS membrane is depolarized glutamate is present IE. you need AMPA next to NMDA to have a slight depol and open NMDA (see next question) This process leads to long-term potentials. Increased Ca++ through NMDA receptors leads to increased PKC which leads to more AMPA receptors. (in dendritic spine formation, NMDA are the first receptors, which trigger 2nd messengers, which then adds AMPA to the terminal.) requires high frequency of action potential, Ca coming in activates PKC which will shuttle more AMPA receptors to the postsynaptic density
2. For each of the following ionotropic receptors, indicate A) The endogenous ligand (neurotransmitter) that activates the channel B) Which ions pass through the channel C) Whether activation of the receptor causes an EPSP or IPSP. Ionotropic receptors: • NMDA receptors • AMPA receptors • Kainate receptors • GABAA receptors • Glycine receptors • Nicotinic ACh receptor • 5-HT3 receptors (this ionotropic serotonin receptor is a Na+ and K+ channel)
NMDA: glutamate, sodium potassium and calcium, excitatory AMPA: glutamate, sodium and potassium, excitatory Kainate: glutamate, sodium and potassium, excitatory GABAa: GABA, chloride, inhibitory Glycine: Glycine, ?, inhibitory Nicotinic: ACh, sodium and potassium, excitatory 5-HT3: serotonin, sodium and potassium, excitatory
12. Could an axon be completely myelinated (without nodes of Ranvier)? Explain your answer.
No, the electrical signal dissipates with distance, so, by the time it got to the end of the axon, there would be nothing left.
Describe the organization of a node of Ranvier. State where specific proteins are located within and around the node.
Node contains voltage gated sodium channels. Paranode is directly next to the node. It contains Caspr2 (an adhesion protein) to keep the edges of the myelin sheath down. Juxtaparanode the rest of the myelin covered axon. contains voltage gated K+ channels.
Memorize and be able to apply Ohm's law. Define conductance (gamma or g) and show how it can be substituted into Ohm's law.
Ohm's law: V=IR. Conductance is 1/R, so I=gV.
6. Interpret voltage/current graphs like those in textbook figure 5-4. Describe the difference between ohmic channels and rectifying channels.
Ohmic channels follow Ohm's law (I= V/R) and have linear voltage current graphs. Rectifying channels allow flow more easily in one direction. Graphs are not linear.
1. Describe the voltage clamp technique. (See textbook pages 150-151)
One internal electrode measures membrane potential (Vm) and is connected to the voltage clamp amplifier Voltage clamp amplifier compares membrane potential to desired (command) potential When Vm is different from the command potential, the clamp amplifier injects current into the axon through a second electrode. Therefore membrane potential = command potential. The current flowing back into the axon, and thus across its membrane, can be measured here. You control the voltage of the cell. It's used to study properties of channels. If you hold the voltage constant it's much easier to study voltage gated channels (in vivo voltage is all over the place)
3. Describe the x-ray crystal structure of the voltage-gated potassium channel. Include a detailed description of the pore and the voltage sensor. (See textbook pages 164-167 and figure 7-15)
Open conformation is the most stable, but the usual negative ICF pulls the S4's positive charges down. When the ICF becomes more depolarizes, then that pull is weakened, and the proteins assumes its most stable, open position. Sensor (S1-S4)- when open, moves into the membrane from the cytoplasm. alpha helix in between S4 and S5 (4-5 helix) is the part that actually yanks the S5 helix over and allows S6 to hinge open Pore - (S5-S6) - cytoplasmic side all shifts outward, opening a pore.
State the difference between orthodromic and antidromic action potential conduction. Under what experimental conditions does antidromic conduction occur? When does antidromic conduction occur naturally (hint: think of nociceptors)?
Orthodromic: Going down the axon, the way we've always studied it. Antidromic: Action Potential is going toward the dendrites. Starts from the axon terminal. ex. in nociceptive (pain) neurons. Before getting to the spinal cord, a second signal travels up to the end of a dendrite and tells the blood vessel to inflamme.
2 main types of neurotransmitters
Peptide neurotransmitters and small neurotransmitters
Define and describe the three basic properties of neuronal ion channels: permeability, specificity, and gating.
Permeability: How much of an ion gets through. Specificity: How many types of ions get through. Gating: how the channel opens and closes.
Explain how CSF is produced. Include a description of the location and anatomy of the choroid plexus in your answer.
Produced in the Choroid plexus in all ventricles. Vitamines and such are actively transported into epithelial cells and enter the ventricles through facilitated diffusion.
9. Summarize the two major mechanisms by which ion channels become inactivated (see figure 5-7).
Prolonged depolarization, Ca++ and calmodulin (Calcium channels only)
7. Explain why axonal transport is important for neurons.
Proteins are produced in the soma. The axon degenerates if protein supply is cut off.
1. Review the meaning of the term resting membrane potential (RMP). State the numerical value of a typical neuronal RMP. Review the meaning of the terms depolarization and hyperpolarization. (See textbook page 127)
RMP= voltage difference across membrane of an unstimulated cell. typical= between -60 and -70 mV -64.1 -70 to -60 mv (the outside of the cell is defined as 0) Resting membrane potential is the membrane potential of a cell at rest Depolarization - A reduction/reversal of charge separation leading to a less negative membrane potential. Hyperpolarization - An increase in charge separation leading to a more negative membrane potential. Almost always passive (do not lead to opening of gated ion channels)
Describe how blood flow in the CNS is regulated.
Regulated in the CNS by sensing change in systemic pressure: Increase in pressure, global arteriole constriction. Decrease in pressure, arteriole dilation Also responds to changes in blood chemistry. Dilation: Increased CO2, decreased pH, decreased O2. Constriction: Increased O2, pH, decreased CO2 Both Global and local responses: Global - blood pressure rises, arterioles constrict (counterintuitive) blood pressure falls, arterioles dilate Local - Co2 inc. -> dilation Co2 dec -> constriction
State the reversal potential for non-specific cation channels (see textbook figure 9-7b). Know that ionotropic glutamate receptors (NMDA, AMPA, and Kainate), nicotinic ACh receptors, and ionotropic 5-HT3 receptors all fall into this category of channels. Explain why opening these channels causes an EPSP when a cell is at resting membrane potential.
Reversal potential for nonspecific cation channels is 0 mV Why does it cause an EPSP at RMP? @ -65mV, K+ has a very small outward flux, while Na+ has an extremely strong inward flux. So if the channel opens, tons of Na+ will come in, but just a bit of K+ will leave. Excitatory Ionotropic Receptors are Non-Specific Cation channels Nonspecific cation channels to know about that fall in this category (Na/K permeable) Glutamate: NMDA (also permeable to Ca), AMPA and Kainate Ach: Nicotinic Serotonin: ionotropic 5-HT3
7. Know the reversal potential and ionic conductances (which ions flows through the channel) of the nicotinic ACh receptor.
Reversal potential is 0. Na+ and K+ ions flow through. The reversal potential is at 0 (the channel is permeable to both K+ and Na+ equally so the reversal potential is similar to the average between each of their individual equilibrium potentials) non specific ion channel Differences between action potential and end plate potential: AP uses voltage gated channels that recruit their neighbor channels in an all or none response End plate potential is produced by Ach channel that acts independently of others (more Na influx through Ach does not recruit neighboring channels to open as well)
4. Detail how the voltage sensor of the voltage-gated potassium channel causes the channel to open and close. (See textbook pages 166-167 and figure 7-16)
S1-S4 is the voltage sensor (all stuck together). S4 is the one that actually has positive charge on it. the more stable conformation is open, when some of the positive charges are exposed to the aqueous ECF and the others are paired with negative AAs on another helix. When the inside of the cell is negative enough, the positive AAs are pulled into the membrane by the charge, which yanks on the 4-5 helix, which pulls on S5. S6 is the one that lines the pore, and it has a glycine residue that wants to hinge open, but S5 is usually in the way. When the 4-5 helix pulls on S5, S6 is then able to hinge open and ions can flow.
Too much dopamine (in the limbic forebrain)
Schizophrenia
Identify and label the following arteries on various diagrams. Know the brain regions to which each artery supplies blood. • Internal carotid arteries • Anterior cerebral arteries • Middle cerebral arteries • Vertebral arteries • Basilar artery • Posterior cerebral arteries • Cerebellar arteries • Anterior communicating artery (know the location) • Posterior communicating arteries (know the location) • Circle of Willis (comprised of several of the above arteries)
See Lecture slides
3. Explain the terms sensory neuron, motor neuron, interneurons (including relay/projection interneurons and local interneurons).
Sensory Neuron: An afferent neuron that receives and transmits information about the environment to the CNS. Motor Neuron: An efferent neuron that relays information from the CNS to the muscles to propagate movement. Interneuron: Any neuron that is not afferent or efferent. Relay/Projection Interneuron: An interneuron that travels long distances. Local Interneuron: An interneuron that connects cells locally.
Explain what the current tracings in textbook figures 7-7, 7-8 and 7-12 teach us about the behavior of voltage-gated Na+ channels and voltage-gated K+ channels during the action potential. (See textbook pages 154-155)
Similarities: Both channels open in response to depolarization and as the size of depolarization increases, the probability and the rate of opening increase. Differences: They differ in the rate of opening (Na+ channels open more rapidly, and in their responses to prolonged depolarization. Inactivation = The process by which Na+ channels close during a prolonged depolarization. Depolarization causes three different states: resting activated inactivated (Potassium doesn't inactivate)
16. Explain the molecular structure and the functioning of the K+ channel as determined by Rod MacKinnon (see textbook pages 116-119 and figures 5-15 and 5-16).
So again on the outside is S5 which has a long loop of amino acids (negatively charged) that create the selectivity filter which is then connected to S6 (inner part of channel). the pore loop section has an α-helix part with a dipole on it. the dipole created from the open state also stabilizes the open conformation.
State specifically how nicotine, curare and a-bungarotoxin affect ligand-gated ACh receptors/channels.
So we got these two receptors right. Nicotinic and Muscarinic. AcH acts on both. Difference is Nicotine stimulates the nicotinic one and Muscarine the muscarinic one. Nicotine - just answered that Curare - antagonist for the nicotinic receptor a-bungarotoxin - also an antagonist for the nicotinic receptor (irreversible)
Explain the following regarding the molecular structure and functioning of ionotropic glutamate receptors (NMDA, AMPA, Kainate).
State how many subunits are found in a receptor and how many transmembrane units are found in each subunit. 4 subunits - each subunit has 3 transmembrane regions (M1-M4) with M2 being the pore loop · Explain the overall structure of an individual subunit including the amino terminal (modulatory) domain, ligand binding domain and transmembrane domain (including M1-M4). State the roles of M2 and M3 in the transmembrane domain. 4 subunits with 3 transmembrane domains For each subunit, the Amino side of the peptide is extracellular. The ligand binding domains are also extracellular and come before M1 and between M3-M4. M2 is the Pore Loop - ion specificity M3 is the linker. When Glutamate binds to the ligand binding domain, it pulls M3 apart and opens the channel · Explain how the ligand-binding domain acts as a clamshell When the glutamate binds the D2 (ligand binding domain), and because it is linked with M3, M3 pulls up as well. M3 being pulled up opens it. · Give details about what is known about the mechanism of activation and desensitization of the receptor/channel. Activation: Glutamate binds D2, changing the conformation to pull up (along with M3). Desensitization: When open for long periods: Too much stress on linker breaks the D1 dimer, so it topples over like a falling building, closing the channel (even when glutamate is present!) desensitization involves rupture of the D1-D1 dimer interface (D1= amino terminal domain) If there are 4 subunits, does it take 4 Glu molecules to activate the channels??? No.Only 2 of them bind glutamate, 2 of them bind glycine. Since theres more or less always glycine present in the ECF, it only takes 2 glycines to activate.
20. Explain what a compound action potential is and how it is measured. Also, discuss how compound action potentials measured during a nerve conduction study can help clinicians. (See textbook pages 477-479 and textbook figure 22-3)
Stimulate near wrist and see effect near the elbow/shoulder. Increasing levels of stimulation will illicit different proprioception to pain sensation (lowest stimulation will cause AP's in Aalpha, next to have AP's will be Aalpha and Abeta, etc.) Although all of these AP's start at the wrist at the same time, they arrive at the elbow at different times so we see different peaks that correspond to each class of neurons.
Know that GABAB receptors are metabotropic and that activation of GABAB receptors results in the opening of K+ channels, causing an IPSP.
Summary: GABAa = Cl- channel (ionotropic and inhibitory) GABAb = K+ channel (metabotropic and inhibitory) GABAb are usually found on the presynaptic side. They shut down the cell if its releasing too much NT.
biogenic amines
Synthesized from amino acids by decarboxylation. Also called monoamines.
5. Review the anatomy and physiology of the knee-jerk reflex.
Tapping the knee-cap pulls on the tendon of the quadriceps femoris. when the muscle stretches in response to the pull of the tendon, information regarding this change in the muscle is conveyed to the CNS by sensory neurons. in the spinal cord the sensory neurons form excitatory synapses with extensor motor neurons that contract the quadriceps. the sensory neurons act indirectly, through interneurons, to inhibit flexor motor neurons that would otherwise contract the opposing muscle, the hamstring.
Define temporal and spatial summation. Explain how a neurite's time constant and length constant affect summation at the axon hillock. (See textbook pages 227-228 and figure 10-14) Last test:
Temporal- low time in between AP's -> more mV change at hillock (repeated action potentials from same area) Spatial- multiple synapse EPSP's adding together from different areas (multiple action potentials from different areas at the same time) Time constant- depends on capacitance. How much time does it take to charge the capacitor and move to next segment of axon. LOW means fast Length Constant- distance where 67 percent of charge is leaked out. HIGH mean fast For temporal summation to work, we want a high time constant and for spatial summation to work we want a high length constant
Explain what an end-plate potential is and why curare must be used when experimentally studying end-plate potentials
The EPSP at a neuromuscular junction. Curare is used because the end-plate potential is so large, that an action potential will fire unless we antagonize the junction.
13. Summarize the concept of "plasticity" (see page 37).
The ability of the brain and synapses to change. This is fundamental in learning and memory.
11. In a myelinated axon, compare the values of Cm and Rm at nodes of Ranvier and internodal regions. Explain why these properties cause "saltatory" conduction of action potentials.
The capacitor of the membrane is the first place that the charge goes. THEN the charge can either travel down the neurite or it can leak out through the membrane (Rm). It travels down the path of least resistance. Axial resistance is the resistance of the fluid of the neurite. Myelination decreases Cm and increases Rm. positive ions flow in and then charge the capacitor. the rest flows down the neurite. Rm = membrane resistance Ra = axial resistance myelinated axons have little capacitance. at the node (high membrane capacitance, low membrane resistance. slows current down), channels are also typically located at the nodes. very little charge leaks out at myelinated areas. high membrane resistance. action potentials then move fast through the myelinated areas and slow through the nodes.
2. Explain in your own words how an ion's chemical driving force (concentration gradient) and electrical driving force (electrical gradient) affect the ion's movement across a membrane
The concentration gradient drives the concentration to be equal inside and outside of the cell. The electrical gradient drives ions toward the side of the membrane that has the opposite charge in order for the voltage to be zero across the membrane.
3. Explain in your own words the meaning of the term "equilibrium potential".
The equilibrium potential is when the concentration gradient driving ions one way and the electrical gradient driving them the other way are equal, resulting in no net flow of ions.
3. State the reversal potential for non-specific cation channels (see textbook figure 9-7b). Know that ionotropic glutamate receptors (NMDA, AMPA, and Kainate), nicotinic ACh receptors, and ionotropic 5-HT3 receptors all fall into this category of channels. Explain why opening these channels causes an EPSP when a cell is at resting membrane potential.
The reversal potential is 0. they cause an EPSP because sodium is farther away from its reversal potential, so it flows in faster than potassium can flow out.
2. Explain why axons in the periphery regenerate better than those in the central nervous system
The schwann cells form a sheath that promotes regrowth. Astrocytes in the CNS block growth pathways and release growth inhibitors.
2. Review the x-ray crystal structure of the bacterial potassium channel KcsA as elucidated by Rod Mackinnon. (See textbook pages 116-119 and figure 5-15). Explain the difference in structure between an open and closed bacterial potassium channel. (See textbook figure 5-16)
The structure provided insights into the mechanisms by which the channel facilitates the movement of
15. Explain what is known about the structure of voltage-gated Na+ channels and voltage-gated K+ channels. In your answer, include the number of subunits and the number of transmembrane regions in each subunit. (See figure 5-11C, figure 5-12A, and pictures from the lecture handout)
The voltage gated sodium channel has four repeated motifs each with six transmembrane regions and a 5-6 loop. S4 is the voltage sensor and the loop between s5 and s6 is the ion selector. The four loops make the ion pore. The voltage gated potassium channel is basically the same, but all four subunits are separate peptides.
Explain how excitatory glutamatergic synapses are anatomically organized. Where are AMPA and NMDA receptors located? Where are metabotropic glutamate receptors located? What keeps receptors located in the correct location? (See textbook pages 220-222 and figure 10-10)
There is a scaffolding at the postsynaptic density that organizes all this. The PSD-95 (postsynaptic density) attaches to the NMDA and AMPA receptors at the post-syn terminal. The PSD-95 goes further inside the neuron and forms a chain with GKAP, Shank, and Homer. Shank and Homer connect to the metabotropic channels on the side of the dendritic spine. metabotropic glutamate receptors are only activated on the side of the synapse if there is excess neurotransmitter (perisynaptic)
10. Briefly describe how glial cells myelinate axons. Briefly describe the molecular composition of myelin. Know the typical internode distance in a myelinated axon.
They wrap around axons. concentric circles. 70% lipid, 30% protein. 1-1.5 mm between nodes.
1. Explain how the behaviors of voltage-gated Na+ and K+ channels and the resulting changes in gNa and gK produce the following properties of action potentials. (You may want to review material from Neuro 205 and/or your physiology course when answering this question). • Threshold • Rising phase • Falling phase • Undershoot (after-hyperpolarization) • Absolute refractory period • Relative refractory period
Threshold: due to the threshold of voltage gated sodium channels. Rising phase: opening of sodium channels Falling phase: closing of sodium channels, and opening of potassium channels Undershoot: Sodium channels are closed, but potassium channels are still closing.
Describe the structural differences between brain capillaries and general body capillaries.
Tight junctions instead of fenestra and intercellular clefts. Pericytes and astrocytes surrounding capillary.
Describe the normal composition of CSF. Explain what the following abnormal CSF findings may indicate: high protein content, high cellular content.
Very low protein, Low glucose, low in all minerals except Na+(=) and chloride (high), slightly lower pH, vitamin c, nucleosides, folates, vitamin b6 High protein: Cell death, disease, infection, breach in BBB Cells: Cancer, Blood leak, infection
Explain how hydrophobicity plots can be used to help deduce the structure of an ion channel. (See figure 5-10 and slides on the lecture handout).
Transmembrane regions will be more hydrophobic than regions that stick out of the plasma membrane.
2. Be able to classify neurons as unipolar, pseudounipolar, bipolar, or multipolar. Know where in the mammalian nervous system each classification is typically found.
Unipolar: dendrites and axon on same branch (Autonomic Nervous System) Simplest, single primary process which gives rise to many branches. In invertebrates = dominates entire nervous system. Pseudounipolar: dendrites and axon on same branch but opposite ends (touch, pressure, pain) Variants of bipolar cells. Develop initially as bipolar cells, but the two cell processes fuse into a single continuous structure that emerges from a single point in the cell body. Axon splits into two branches - one to the periphery (sensory receptors in the skin, joints, and muscle) , the other to the spinal cord. Bipolar: axon and dendrites on opposite sides and different branches (sensory, retina, nose) Oval soma with two distinct processes: a dendritic structure (receives signals from periphery) and an axon (sends info to CNS) Extent of branching correlates with number of synaptic contacts Multipolar: dendrites coming out of cell body (motor, cerebellum) Predominate in the nervous system of vertebrates. Typically, a single axon and many dendritic structures emerging from various points around the cell body,central nervous system
vesicular ATPase
Uses ATP to establish a H+ gradient by pump H+ ions into the vesicle.
4. Memorize the Nernst equation and, given specific concentrations of ions across a membrane, be able to calculate an ion's equilibrium potential.
V=RT/Fz ln([out]/[in]) V=58/z*ln([out]/[in])
Explain the causes and effects of vasogenic edema, cytotoxic edema, and hydrocephalus
Vasogenic edema: brain swelling. Plasma escapes through the BBB. Caused by Brain trauma, contusion, tumors, focal inflammation, break-down of BBB. Cytotoxic edema: influx of Sodium into neurons, depletion of extracellular Na+, Cell death. Caused by Hypoxia, Ischemia (cardiac arrest), water intoxication Hydrocephalus: Excess Ventricular CSF. Caused by overproduction of CSF, blockage of CSF flow, impaired drainage of CSF. Causes intracranial pressure in adults and head enlargement in children.
6. Describe the molecular composition of intermediate filaments. Know the names of intermediate filaments that are found in neurons and glial cells.
Very stable. Complex arrangement of coiled dimers. In neurons: Neurofilaments. In glial cells: Glial Fibrillary Acidic Protein (GFAP).
8. When given an unknown channel to study, explain how you would determine what ions the channel is permeable to.
You could use a voltage clamp experiment where you plot ion flow and see where the reversal potential is. When you determine reversal potential, you could identify to what equilibrium potential it is closest to. This way you can determine what ion is most permeable. MEMORIZE the reversal potential of each ion channel? ←-Anyone figure out the answer to that? its a good question... If the Ion shifts when you change the concentration, the ion is permeable. If it doesnt shift, it is NOT permeable. Lower Na+ and ACh graph shifts Left, Increase K+ and graph shifts to the right.--> ACh graph shows translation of graph to both Na+ and K+, therefore permeable to both. (Typically not permeable to calcium but can be)
4. Explain what will happen when the following RC circuit is closed. Explain what will happen when the circuit is opened again. How does current flow through this circuit relate to neuronal membranes?
current will first flow out of the positive end to the capacitor. once the capacitor is charged, the remaining charge will flow to to the resistor. once the circuit is again disconnected, the capacitor discharges. In neurons it works the same way. current flows down the axon, when arriving at a node it depolarizes the cell and opens up the gates. when sodium flows in, it first charges the capacitor or the membrane and then goes down the resistor or the actual axon.
3. Summarize experiments that demonstrate CNS axons are capable of regenerating in a PNS environment
cut optic nerve, graft peripheral nerve. axons grow.
3. Describe how artificial bilayers are constructed and how they are used to study ion channels. Propose advantages and disadvantages of using artificial bilayers when studying ion channels.
paint a thin drop of phospholipid bilayer over a small hole of a non-conducting barrier between two salt solutions. By adding gramicidin channel (a 15 AA cyclic peptide), we increase the permeability of bilayer to ion flow. They were able to show an all-or-none type of system where the greater the membrane potential, the greater the current. Application of low concentrations of gramicidin A brings about small changes in current across the membrane. Advantages? Provides info on channel function like the all-or-none type of system Disadvantages? Does not resolve the small amount of current that flows through a single ion channel. Advantages: You get to control how much, ratios and kinds of channels in your membrane. Disadvantages: very low ecological validity.
4. Describe the patch clamp technique. Propose advantages and disadvantages of using the technique to study ion channels. (See Box 5-1 on textbook page 106)
pipette with very small diameter is clamped over a single ion channel. pipette is full of a salt solution resembling extracellular fluid. special electrical circuit is connected to pipette to measure current through channel Advantage - Can study all three classes of ion channels - voltage-gated, ligand-gated, and mechanically-gated... measures the current of these individual channels. Disadvantage - can't access certain membrane channels and aren't able to determine composition of membrane lipids around channel and understand its effect
Not much is known about these neurotransmitters
purines
false neurotransmitters
recognized by the transporter, but not by the postsynaptic receptor