Neurobiology Test 1 (Chapters 1-5)

Cerebellum

"LittleBrain" * Functional debate *Motor control, Sensory acquisition, Proprioception (balance) * Coordination of motor control and cognitive ability (some verts) Most caudal component (at the back of brain) Part of the hind brain

Sensitization

(G protein breaks off and activates A strong stimulus can bring back the gill withdrawal reflex With a noxious stimulus, gill reflex is potentiated (strengthened reflex response)(quicker, with more force, stays withdrawn longer) Sensitization: A form of non- associative learning in which a strong (usually noxious) stimulus enhances the response to a variety of subsequent stimuli -Now when you lightly touch siphon you will see a strengthened response 1. Input from the skin receptors activate Sensory Neuron 2 (Sensory neuron 2 sends info to interneuron that synapses on neuron 1) 2. The synapse on a facilitating interneuron, that excites sensory neuron 1 via serotonergic response synapses 3. Activates the motoneuron 4. The consequence of the sensitization process is to increase the size of the EPSP in the motoneuron 5. Thus, gill withdrawal is stronger and more forceful Increase in amount of syneptic vessicles ncrease in the duration of the action potentials *Because the change in EPSP amplitude is mainly due to neurotransmitter release, the change is said to be Presynaptic Serotonin is released at the presynaptic terminals of the sensory neurons in the gill withdrawal circuit Blocking serotonin receptors on those sensory neurons prevents the ability of the tail shock to induce sensitization Adding serotonin onto the sensory neuron can sensitize the gill withdrawal reflex without a tail shock

Long Term Depression

(LTD) : A form of synaptic weakening that can last for many hours following certain patterns of presynaptic stimultion (neurons that fire together get weaker?) *Anti-Hebbian Plasticity: A learning rule by which synaptic plasticity can be controlled Best studied form of synaptic weakening is Cerebellar LTD *Functional Debate *Fine tuner of movement *Motor learning *Error adjustment Activating the parallel and climbing fiber inputs simultaneously, and repeatedly, causes the parallel fiber input to decrease in strength Ca2+ triggering in the cerebellum is a critical mechanism involved in long-term depression *Parallel fiber terminals and climbing fibers work together in a positive feedback loop for invoking high Ca2+ release

Hodgkin-Huxley model

(Nobel Prize, 1963) GIANT SQUID : One of our key findings was that, at the beginning of an action potential, the axonal membrane suddenly becomes highly permeable to Na+ ions At rest, permeable to K+ but not sodium *At the beginning of an action potential, the axonal membrane suddenly becomes highly permeable to Na+ ions *Rising Phase: Voltage-gated Na+ channels open & allow Na+ ions to flow (K+ starts to move out) Depolarization: Negative internal charge of cell becomes briefly positive Na+ ions flow down concentration gradient into the cell Increasing polarity = depolarization thanks to increase in Na+ *Increases the probability the neuron will fire an action potential

Synapse

* Synapse: the junction/gap between the terminal of a neuron and either another neuron or a muscle or gland cell, over which nerve impulses pass -3 nm (electrical) to 40 nm across Depend on mode of synaptic transmission

Aplysia Californica

*Eric Kandel: 1960's *Small number of very large neurons (~20,000) *A variety of behaviors that can be modified as a result of experience When Aplysia is relaxed, the siphon and gills are visible from above When that siphon is touched gently, structures are temporarily withdrawn and covered with protective flap (reflexive behavior) Siphon: Draws water over gills and expels waste Siphon and gill withdrawn, protective from debree, strong curent, etc. Sea hair Anatomy: Respiratory chamber covered by mantle shelf Reflex can be triggered even when the body is dissected away *Even innate reflexes can be modified by experience *Repeated exposure to the eliciting stimulus can either decrease (habituation) or increase the size of the response

Heterosynaptic vs Homosynaptic

*Heterosynaptic : Activity at one synapse causes a change in the strength of another synapse (aphlysia) *Homosynaptic : Activity at one synapse causes a change in the strength of same synapse (mammals)

Auditory Cortex: Tonotopic Map

*Like dendritic spines, axons are also highly dynamic*Axons can sprout new branches, even in intact, adult brains *Map plasticity Compared the stimulus preferences of neurons in the primary auditory cortex of naïve (untrained) and trained rats * The frequency of the conditioned stimulus (the tone) is overrepresented relative to naïve rats *Trained thirsty rats to push bar when they heard 6 kHz to get water (Then compared auditory cortexes, and found that other frequencies became underrepresented) Training alters the tonotopic map *Neurons shift their response preferences as the animals learn the association between the 6Hz tone and water availability *Cortical neurons shift their response preferences towards the conditioned stimulus, over-representing the stimulus frequency on the map Activation of visual cortex in blind people when using echolocation

Snare Proteins

*Snare proteins= Mediate vesicle fusion *v-SNARES (vesicular receptors)*Synaptotagamin & Synaptobrevin*Embedded in the vesicles (holding neurotransmitters) *t-SNARES (target receptors)*SNAP-25 & Syntaxin *Part of the Presynaptic membrane (Needs to get there to fuze) Cytoplasmic Proteins *NSF: N-ethylmaleimide-Sensitive factor *SNAPs: Soluble NSF attachment protein (Glue: Wrap around snares) 1. Target membrane: Ca2+ binds to Synaptotagamin (initiates movement of vesicle to pre synaptic membrane) 2. V snares tether to t-snares (vesicle docked to membrane) 3. NSF and SNAP help form complex 4. Opening of fusion pore (in presynaptic membrane, releasing neurotransmitters into synaptic cleft) 5. Unfolding and release of SNARE proteins

The Chemical Synapse

1.Action potential arrives at axon terminal 2. Voltage gated Ca2+ channels open and Ca2+ enters the axon terminal 3.Ca2+ entry causes neurotransmitter-containing synaptic vesicles to release their contents by exocytosis 4.Neurotransmitters diffuse across the synaptic cleft and bind to the receptor protein on the post-synaptic membrane 5. Binding of neurotransmitter opens ligand-gated ion channels, resulting in graded potential 6.Reduction of neurotransmitter levels, terminating the signal **Excess neurotransmitters leftover in synaptic space need to be neutralized -This can happen one of three ways: 1. Reuptake by the presynaptic neuron 2. Enzymatic Degraded (e.g. acetylcholinesterase) 3.Diffusion out of cleft

Tetanic Stimulation

1950's, Mammalian spinal cord *High frequency repetitive stimulation of sensory spinal nerves can strengthen the responses of spinal motor neurons to sensory inputs *A form of electrical stimulation in which many short electrical pulses are delivered at a high frequency Post tetanic Stimulation: A form of synaptic plasticity that is observed after tetanic stimulation but lasts only for a few minutes *Isn't sufficient enough for long term memory *shows form of short term memory in spinal cord of post synaptic cell

Extra/ Overall themes

30,000 genes in human genome 1-2% expressed uniquely in the brain *Nervous system has a molecular toolkit shared broadly with cells in other body parts Neurotransmitter receptors are more diverse then the neurotransmitters PP 1: The vertebrate Nervous system is divided into two systems: the Central and Peripheral Nervous System *The central nervous system is divisible into brain and spinal cord (+ retina) *Important orientation terms: dorsal, ventral, superior, inferior, ipsilateral, contralateral, sagittal, axial, and coronal *The nervous system contains neurons and glial cells. The neurons have distinctive dendrites, axons, and synapses. Despite these specializations, only 1-2% of human genes are "brain-specific" *Neural circuits tend to be replete with diverging, converging, and reciprocal connections PP2: Neural circuits tend to be replete with diverging, converging, and reciprocal connections * The brain is comprised of the forebrain, midbrain, & hindbrain, which consist of even smaller subdivisions (and serve different functions) * Forebrain: Diencephalon (Preoptic Area, Retina, Hypothalamus, Thalamus) & Telencephalon (Cerebral Cortex, Olfactory Bulb, Telencephalic nuclei) * Telencephalic nuclei: Pallidum, Striatum, Septum, Amygdala * Cerebral Cortex: Piriform Cortex, Neocortex, Hippocampus* Midbrain: Collicui (Superior & Inferior), Tegmentum* Hindbrain: Cerebellum, Pons, Medulla PP3: *The characteristic features of a "typical" neuron *Most cells maintain an internal environment that is negatively charged compared to the cell's surrounding environment *Neurons have an inside-negative resting potential that is temporarily reversed during action potentials. *Action potentials propagate by internal current flow that decays exponentially with distance but can trigger successive membrane patches to fire all-or-nothing action potentials PP4 *Neurons vary in terms of their neurotransmitters, receptors, and ion channels* Sensory, motor, interneuron* Monopolar, bipolar, multipolar* Excitatory vs. inhibitory neurotransmitters* Ionotropic receptors (K, AMPA, NMDA) vs. Metabotropic receptors *Sensitization of the gill withdrawal reflex involves the release of serotonin onto presynaptic terminals in a simple sensorimotor circuit (short-term sensitization) *Long-term sensitization requires new protein synthesis* A crucial factor is the phosphorylation of CREB PP 5: *Synapse strengthening (potentiation) in mammals is commonly induced by high-frequency repetitive (tetanic) stimulation of an input pathway. *Long-term potentiation (LTP) is characterized by an increase in EPSP amplitude that persists for several hours (or more) after the end of the tetanic stimulus. *LTP is associative when it obeys Hebb's rule, which states that synapses should only be strengthened when presynaptic activity is accompanied by post-synaptic depolarization, which may trigger action potentials. * The best studied form of synaptic weakening is cerebellar long-term depression (LTD) * LTD involves metabotropic glutamate receptors and the removal of AMPA receptors from the postsynaptic membrane. * Dendritic spines may sprout or disappear in adult brains, and changes in the rate of spine turnover may correlate with learning. Axonal branches may also sprout as animals learn. * As animals learn important new information, the cortical territory representing that information tends to expand at the expense of territory representing less important information. * Sensory and motor maps PP7 Theembryo's ectoderm givesriseto both skin and the nervous system, the latter being the ectoderm's default fate (BMP VS Chordin) *Rostrocaudal patterning in the hindbrain and spinal cord involvesretinoic acid. Without these caudalizing signals, the neural tube tends to form rostral brain regions Floor plate cells secrete SHH, which induces some transcription factors and represses others in a concentration-dependent manner. * Mutual repression between transcription factors creates distinct dorsoventral compartments with sharp boundaries Dorsoventral domains are established by opposing concentration gradients of SHH and BMP

Hydrocephalus

A condition in which there is an accumulation of cerebrospinal fluid within the brain ("water on the brain") Any blockage in the flow of CSF from the choroid plexus to the subarachnoid space increases intraventricular pressure CSF can be dangerous

Long-Term Potentiation

A form of synaptic strengthening (potentiation) that is observed after tetanic stimulation and lasts for many minutes, hours, or even days *Elicited not just in synapses of the perforant path, but in several other hippocampal pathways Hippocampal LTP is homosynaptic (only the stimulated, active synapses are strengthened) *Hippocampal LTP involves mainly post synaptic change Aphlysia dont really look at motor neurons (post) (Only heterosynaptic)

Saltatory Conduction

Action potentials can "jump" from one node of Ranvier to another further down the axon *Increases the speed of action potential propagation Parts covered in myelin don't need to be depolarized (only need to depolarize nodes of ranvier)

Propogation Speed

Action potentials travel relatively slowly (compared to the way electrical signals travel down copper wire) *Propagation speed is dependent on several things: *Time is takes voltage gated Na+ channels to open *Time it takes for Na+ ions to flow into axon *Time for successive patches of axonal membrane to reach the threshold for action potential triggering

IPSP (Hyperpolarization)

Amplitude of IPSP is directly proportional to the number of synaptic vesicles released Change in the cell's m*embrane potential that makes it more negative Inhibits action potentials K+ Out, Cl- IN Repolarization: Na+ close, K+ opens, K+ leaves, cell at -75 mV Example of IPSP: Gamma aminobutyric acid (GABA): Usually inhibitory Ligand gated Cl- channels: Cl- enters, resulting in hyper polarization (Inhibits firing of action potentials)

Action Potential

An all-or-none electrochemical signal generated by neurons in response to above-threshold stimulation (Travels down axons) -Brief reversal of polarity of the membrane potential -70 jumps to +40 (how neurons transmit info along axon) Sweeps along the membrane of a neuron (+40mV) *Alan Hodgkin & Andrew Huxley (created model of newborn excitability) -Transfers info *Action potentials are "All Or None" *Varying degrees of depolarization but not action potentials Travels along axon as long as those sites are not in the action potentials wake (refractory) Action potential propagation is directional (away from axon hillock) Refractory period: A period following an action potential when the neuron cannot generate another action potential

Neuron (4-5 micrometers or larger, need to be able to house organelles)

An electrically excitable cell that processes and transmits information through electrical and chemical signals Dendrites RECIEVE signals: Get thinner as they move away from soma Axon originates at axon hillock where action potential originates *Axons are generally no thinner than 0.1 micrometers in diameter Axon collateral is the 1 major branch Terminal Arborizations all have the same width *Cell body = soma *Double layered lipid membrane *Central nucleus (with nucleolus inside) * Glial Cell: Non-neuronal cells in the brain (maintain homeostasis, provided structural support) *Mitochondrion: Oxidative metabolism/ATP Specialization: *Rough ER = Nissal substance (job is to synthesize new membrane) * Micro- & Neurofilaments, Microtubules (form cytoskeleton/help with structure)

Neurotransmitter

Any substance responsible for sending nerve signals across a synapse between two neurons

Telencephalon (cerebrum) (Makes up 1/2 of our brain)

Area of forebrain divided into cerebral cortex, olfactory bulb, and telencephalon nuclei Cerebral Cortex (gray matter) divided into Piriform cortex, neocortex (Frontal lobe, parietal lobe, occipital lobe, temporal lobe), and hippocampus Olfactory Bulb: Purely sensory (receives input from the olfactory epithelium) Telencephalon nuclei divided into Pallidum, striatum, amygdala, and septum Also contains corpus callosum (millions of axons) which allows L and R hemispheres to communicate

The Developing Brain

As development proceeds, different cells come to express different sets of genes *Sea anemone embryos* As development proceeds, Beta-catenin expression becomes restricted to one side of the embryo (ie, new cells are expressing different genes) Transcription Factors: A protein that binds to short, specific sequences of DNA and regulates the expression of downstream genes *Regulation of gene transcription *ie, CREB *Cell fate : The kind of adult cell that a young cell will become

Action potentials are initiated in the ___________

Axon Hillock (small mound below soma) *High density of voltage-gated Na+ channels *First place that reaches the threshold for action potential initiation

Similariteis between AMPA and NMDA

Both are ionotropic Both open to glutamate (NMDA opens to NMDA too) Both allow flow of sodium and potassium (But calcium can flow thorugh NMDA not AMPA) NMDA is both ligand and voltage gated, AMPA is just ligand gated

Central Nervous System

Brain and spinal cord Thalamus is part of the CNS, part of the diencephalon Brain divided into forebrain, midbrain, hindbrain Vertebrate brains are highly centralized Neurons tend to be clustered in one location Allows for more rapid neural communication

During short term sensitization, what is the name of the enzyme that is activated leading to the synthesis of cAMP? A. Phosphlipase C B. Cyclinase C. Adenylane cyclase D. Resporate C

C.

During short-term sensitization in Aplysia, metabotropic serotonin receptors are activated. What is the very next step in the intracellular signaling cascade? a) Increased cAMP levels activate protein kinase A (PKA) b) K+ channels close, broadening the action potential c) The g-protein decouples and activates adenylate cyclase d) More voltage-gated Ca2+ channels open

C.The g-protein decouples and activates adenylate cyclase

Dorsoventral Patterning

CNS is patterned along the dorso-ventral axis *Spinal cord (formed from caudal) * Neurons that send their axons to muscles lie ventrally * Neurons that receive input from sensory nerves are located dorsally Sonic Hedgehog: SHH: A secreted protein that can ventralize cells in the embryonic spinal cord and brain *Further from floor plate = decrease in SHH concentration Ventralizing: To change the developmental trajectory of cells so that they will adopt a more ventral cell fate Forebrain is rostral to the midbrain &midbrain lies rostral to thehindbrain SHH is expressed along the ventral edge of the entire brain *Ventralizing signal throughout the neural tube BMP is expressed dorsally throughout the neural tube (less ventrally)

40 points multiple choice fill in blank 60 points short answer (10 questions, pick 6) Extra credit section

Chapter 1: Nervous System Organization Chapter 2: Computing with Neurons Chapter 3: Neuronal Plasticity Chapter 4: Developing a Nervous System Chapter 5: Protecting & Maintaining the Adult Nervous System

The loss of __________ protein during embryological development would cause the loss of the development of the ____________. A. BMP; Nervous system B. Chordin; Nervous system C. Chordin; Skin D. BMP; the brain

Chordin; Nervous system Chordin inhibits BMP. If BMP doesn't get to bind, it becomes nervous system. If BMP does bind, it becomes skin. No chords means BMP binds.

Concentration Gradient VS Electrical Potential Gradient

Concentration Gradient A difference in the concentration of ions across two sides of a cell membrane (Tries to push K+ out) K+ leaks to move down concentration gradient to even things out Electrical Potential Gradient: A difference in electrical potential between the inside of a cell and its surrounding extracellular space (Intracellular = slightly more negative, so it moves K+ back in) K+ ions fighting against the concentration gradient (push K+ out) vs. the electrical potential gradient (keep K+ in) 1.Initial condition created by Na+/K+ ATPase 2. K+ ions will start to diffuse out along/down their concentration gradient 3. The electrical potential moves the K+ into the cell 4. Equilibrium state The net movement of potassium through all of these mechanisms that sets a neuron's resting potential *Flow of K+ due to Na+/K+ pump (small, into cell) *Flow of K+ into cell due to electrical gradient (Larger) Flow of K+ out of cell fun to concentration gradient (largest)

Myelination Pros and Cons

Decrease in signal transmission time Saves metabolic energy *Good biological design: Evolved several times independently: vertebrates, inverts (ie, earthworms, shrimp) Cons: Myelin isn't entirely cost free (still uses metabolic energy) Myelin is bulky: Takes up space (absent where neurons are tightly packed *Saving wire: rule of thumb (Long axons myelinated, short ones not) -Squid don't have myelin

Hindbrain

Divided into cerebellum, pons, and medulla

Midbrain

Divided into colliculi and tegmentum Colliculi: *"Little hill" *Superior&Inferior colliculus * Superior (tectum) = optic/vision from retina * Inferior: Auditory Tegmentum: Modulation of activity of other brain regions * Orientation reflexes * Posture * Red nucleus & substantia nigra * Partof"brainstem" Below both colliculi Damaged in patients with parkinsons

Forebrain (largest of the three)

Divided into telencephalon and diencephalon

Cerebral Cortex

Division of telencephalon (larger part of forebrain) Cerebral Cortex (gray matter) divided into Piriform cortex (near bottom), neocortex (near top), and hippocampus (near bottom) Organized in discrete layers called Laminae Number of laminae depends on structure in question Piriform Cortex & Hippocampus : 2-3 layers *Neocortex: 5-6 layers

Sequential Depolarization

Domino effect: Depolarization of one part leads to depolarization of next part and so on...... Action potentials travel along axons because the massive influx of Na+ ions at one location of the axonal membrane tends to trigger Na+ influx at adjacent locations 1. When the depolarization reaches the action potential threshold, Na+channels open and Na+ ions flow in 2. The flow of positive ions in depolarizes adjacent regions, opening new Na+ channels 3. The flow of those ions depolarizes the next region, leading to the continuation of the AP

During depolarization, we see a reversal of polarity of cell, primarily due to:

During depolarization, we see a reversal of polarity of cell, primarily due to rapid opening of voltage gated Na+ channels

Electrical Synapse VS Chemical Synapse

Electrical Fewer in number/smaller Mechanically and electrically conductive link (gap junction, 3.5nm) Virtually instantaneous Lack gain Does not require neurotransmitter Some are bidirectional (ions flowing both ways) More reliable, fewer steps Chemcial More common Cell communication via Chemical diffusion (synaptic cleft is a lot larger: 20-40 nm) Depend on neurotransmitter release (1ms delay) Sumamtion Unidirectional (Presynaptic to postsynaptic neuron) More likely to be blocked Electrical and chemical transmission can both occur at same synapse

Santiago Ramon y Cajal (1852-1934)

Electrical signals pass from cell to cell *Santiago Ramón y Cajal improved upon the "black reaction" *Applied the Golgi technique to more diverse material (1887) *Cajal proved Golgi wrong (Celebrity deathmatch: Golgi said brain was web, but he was wrong)) Determined that the processes emerging from cell bodies did not fuse into one mesh Axons and dendrites are separated by gap Dendrites tend to be directed TOWARDS sensory input, Axons directed towards brain center (AWAY from sensory input) Neurons are functionally polarized: Inputs terminating on dendrites and outputs streaming through axons Cajal couldn't have done his work without Golgi *Suggested the presence of contacts between cells used for communication *Observed tiny gaps between axons and dendrites

Nervous System Induction Spermann-Naglod Organizer

Hans Spemann & Hilde Mangold (PhD candidate): salamander development during gastrula stage Dorso Blastopore Lip: (early definition) part of mesoderm that formed much more complete structures than other parts The "Organizer" : a region of the early (gastrula stage) embryo that directs the development of other parts of the embryo *Dorsal blastopore lip : (more complete definition) part of mesoderm that produces molecules that induce adjacent parts of the ectoderm to adopt a Neural cell fate * e.g. emits a signal that induces neighboring cells to develop into a nervous system *Induction: the process by which the identity of certain cells influences the developmental fate of surrounding cells. *Dorsal portions which included the blastopore lip gave rise to complex structures * e.g. notochord, neural tissue and sometimes parts of the head)

Donald Hebb

Hebbian LTP: *Strengthening of neuronal connections occurs between neurons whose activity is associated in time *Donald Hebb, 1949 *Neural basis of thought and memory When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased. - Hebb, 1949 Neurons that fire together wire together (synapses can be strengthened)

BMP and Chordin

Identification of genes expressed selectively in the dorsal blastopore lip Chordin: Diffusible protein that is secreted by the dorsal blastopore lip and capable of inducing the ectoderm to adopt a neural call fate Bone morphogenic protein (BMP): Diffusible protein secreted by cells on the ventral side of the embryo (directs ectoderm to become skin) 1. BMP molecules diffuse away from their ventral source and bind to the ectoderm, they cause ectodermal cells to become skin (When BMP binds to ectoderm it becomes skin) 2. As BMP molecules approach the dorsal blastopore lip, they are inactivated by chordin The dorsal blastopore lip induces nervous system formation by BMP Nervous system is DEFAULT mode Nervous system development lies in an inhibitory signal

Long-Term Sensitization in Aplasia (Requires protein synthesis/new synapses)

If Aplysia is given repeated noxious stimulation to the tail, the sensitization period lengthens considerably -Results in structural changes -Long-term sensitization requires the translation of new proteins from RNA (protein synthesis) -Short term doesn't require new proteins 1. Repeated noxious stimulation lead to repeated release of serotonin and thus high levels of PKA (makes its way to nucleus of sensory neuron) 2. PKA phosphorylates and activates the transcriptional activator cAMP response binding element protein (CREB). 3. Phosphorylated CREB binds to cAMP response element (CRE) sequences that are located upstream of many genes (increases rate of transcription) 4. When bound to the CRE sequence, phosphorylated CREB interacts with nearby RNA polymerases, which begin their task of transcribing the downstream gene 5. The transcribed mRNAs are translated into proteins and shipped from the nucleus to other parts of the neuron 6a. CREB stimulates the synthesis of a gene that codes for the enzyme Ubiquitin hydrolase 6B. Other genes induced by CREB result in production of unknown proteins (building blocks for structural changes) 7a. Ubiquitin hydrolase (goes back to axon terminal) stimulates degradation of the regulatory subunit of PKA (PKA closes k+ channels and opens Na+ channels) 7b. Unknown proteins thought to causes an increase in the size of sensory axon terminals and the addition of synaptic terminals. (can hold more ion channels) 8a. Some PKA is persistently active & no longer requires serotonin to be activated (no longer needs tail shock 9. Process thus yields a long-term increase in number of synapses between sensory and motor neurons (long term memory of enhanced gill withdrawal reflex *Spacing out tail shocks yields increase in # of synapses between sensory and motor neurons (increased EPSP) *Structural changes NOT seen following short term sensitization Number of synapses more than doubles following long-term sensitization

During chemical synapse transmission, entry of calcium into he axon terminal is critical for what part of the process?

Initiates movement of the vesicle tot he presynaptic membrane in prep for exocytosis.

Neocortex (Frontal lobe, parietal lobe, occipital lobe, temporal lobe) Cortical folds called: Cortical valleys called:

Involved in higher functions Latin for "New" *Neopallium and Isocortex *Thin, layered structure *Hallmark of mammalian brains *Division of cerebral cortex, which is division of telencephalon, which is division of forebrain Divisible into Coritical areas *Small Mammals: 12 cortical areas *Humans: 100 cortical areas Cortical folds called: Gyri Cortical valleys called:Sucli The Insula is the 5th lobe (buried beneath the frontal and temporal lobes, kinda in the middle)

Ligand Gated Ion Channel

Ion channels that open or close depending on binding of a specific type of molecule (a ligand) to the channel *Ligand: a molecule that produces a signal by binding to a site on a target protein

Nervous System

Know Flow Chart! A complex network of nerves and cells that carry messages to and from the brain and spinal cord to various parts of the body CNS (brain and spinal cord) and PNS PNS divided into Autonomic NS (Communicates with internal organs and glands) and Somatic NS (Communicates with sense organs and voluntary muscles) Autonomic divided into sympathetic division (arousing) and parasympathetic (calming) SNS divided into sensory nervous system (Sensory input: Afferent) and motor nervous system (motor output: Efferent)

Membrane Potential/Graded Potential

Membrane Potential : The voltage difference between the inside andoutsideoftheneuron(restingpotential:-70mV) 3 ways a cell maintains this resting potential and how they affect movement 1. Flow of potassium out due to concentration gradient 2. Flow of K+ in due to electrical gradient 3. Sodium potassium pump (2 K+ in for 3 Na+ out) Graded potential A small deviation from the membrane resting potential that varies in size *May be Excitatory (Type 1: EPSP) or Inhibitory (Type 2: IPSP) Larger EPSP = Larger depolarization IPSP makes it harder to fire

5 week old embryo neural tube

Midbrain: optic tegmentum Hindbrain: Cerebellum, medulla

Mood Elevating Drugs

Most anti-depressant drugs selectviely inhbit serotonin (involved in mood control) MDMA: EMpathy, euphoria, slows reupatake of things tha make you feel good Massaive release of serotnin followed by massive absence (E hangover) Prozac: Mood elevator * Seratonin reuptake inhibitor *MDMA (3,4-Methylenedioxymethamphetamine):*Ecstacy /E ; Molly* Alters seratonin transport molecules

Myelination

Myelin Sheath: A multi layered wrapper of myelin-rich glial cell membranes around an axon Mode of Ranvier: A small gap in the myelin sheath, usually occurring at regular intervals along axon this is where we can jam sodium and potassium channel (without nodes, action potential would die out) 1. When an action potential is triggered at the axon hillock in a myelinated axon, positive current flows down the segment to the nearest Node of Ranvier 2. Positive current depolarizes the membrane and the Na+ rushes into the axon at the Node of Ranvier 3. The wave of current triggers another action potential 4. Action potentials "leap" from one node to the next

LTP: NMDA receptors

NMDA receptors open only when the cell becomes depolarized because Magnesium ions (Mg2+) block the receptor's central pore *"Coincidence Detectors" : Requires both pre- and postsynaptic events Central pore lets current flow through when glutamate binds AND when the postsynaptic membrane is already depolarized Electrostatic repulsion: Magnesium block is gone A molecular mechanism for detecting the coincidence of presynaptic glutamate release and postsynaptic depolarization -Good mechanism for triggering LTP 1.Binding of glutamate to both NMDA and AMPA receptors (crosses cleft, binds to both) 2. AMPA opens and allows Na ions to flow in, initiating depolarization of the postsynaptic cell 3. Depolarization dislodges the Mg2+ block, allowing Na+ and Ca2+to enter the postsynaptic cell 4. As Ca2+ levels rise, a protein called calmodulin binds to Ca2+ creating a Ca2+/calmodulin complex 5. Ca2+/calmodulin complex activates a protein kinase called calcium/calmodulin kinase 11 (CaMK11) 6. Activated CaMK11 promotes the insertion of additional AMPA receptors into the membrane 7. CaMK11 also phosphorylates the AMPA receptors, which increase the rate at which ions flow in (more Na+ can enter) (More responsive to glutamate) End result: Strengthening of synapse

Neural Tube Fomration

Neural crest: A group of cells that originates at the lateral edges of the neural plate, and migrates away from there to form a variety of tissues, including large portions of the peripheral nervous system *Neural plate : an early stage of neural development when the prospective nervous system is still a flat sheet *Neural groove : an early stage of neural development when the originally flat neural plate has begun to fold lengthwise *Neural tube : an early stage of neural development when the left and right edges of the neural folds meet along the top of the embryo and fuse, forming a tubular structure

metabotropic receptors

No central pore, but open and close nearby channels via intracellular signaling cascades -Indirect effects on ion channels An extracellular domain that contains a neurotransmitter binding site and an intracellular domain that binds to G-proteins.* Indirectly linked with ion channels* Takes longer to develop, lasts a long time Enzyme controls production of second messengers Neurotransmitter released, binds, activates G protein -Subunit of G protein breaks off and activates enzyme, which starts to generate production of second messenger, which opens or closes ion channel Takes longer, but lasts longer

Orientation Nomenclature for humans and non-humans and brain section planes

Non Humans (four legged, like a dog) -Dorsal: Up from back (top of head) -Caudal: Back of brain (rear) -Rostrocaudal: Front to back -Ventral: Stomach, under brain -Dorsoventral: Top to bottom -Rostral: Under chin (face) Humans: Superior: top of head Inferior: Bottom of brain/body Posterior: Butt, back Anterior: Stomach/front Brain section planes: Axial: Slices into top and bottom (up/down): Horizontal plane Coronal: Frontal plane (Front and Hind brain) Midsaggital: Medial plane (left, right) Ipsilateral: on same side Contralateral: On or to the opposite side (most of our brain)

Four types of glial cells

Non-neuronal structure cells in brain Maintain homeostasis and provide structural support Neuron to glia ratio: 1 to 1 CNS Microglia: Smallest, help control brain damage, engulf debris Astroglia: Large, star shaped, nutritive and support function Oligodendrocytes: Asymmetrical, form myelin sheath around axons in brain and spinal cord PNS Schwann Cells: Asymmetrical, wraps around peripheral nerves to form myelin *Myelin is what makes white matter look white

Otto Loewi

Otto Loewi showed that acetylcholine could mimic the effect of vagal nerve stimulation

Increasing axon diameter (like in giant squid) Pros and Cons:

PRO: Increase propagation speed -Larger axons propagate quicker CON: Increasing axon diameter is costly & takes up more space/ metabolic energy SO we wrap it in MYELIN

Hippocampus

Part of cerebral cortex Below neocortex Important in spatial navigation A form of synaptic plasticity that is observed after tetanic stimulation but lasts only for a few minutes *Isn't sufficient enough for long term memory Bliss & Lomo (1973): First to look for evidence for memory-related synaptic plasticity in the hippocampus Rabbit dentate gyrus recordings while applying four high frequency (tetanic) trains of electrical stimuli to the perforant path (Higher EPSP than before tetanic stimulation) Neuronal plasticity studies in "hippocampal slices" *Perforant Path : Major input to the hippocampus from neocortex (set of axons) goes to Dentate gyrus: Part of hippocampus thought to contribute to episodic memories (when/where things happen) Projects to Cornu Ammonis (CA) fields

Thalamus

Part of diencephalon (forebrain) Relay station for sensory input * Lateral geniculate nucleus (LGN) (Input from retina) * Medial geniculate nucleus (MGN)(auditory pathways) * Multiple pathways

Pons

Part of hindbrain * "Bridge" (think bridge goes over pond, sounds like pons...) * Connects the cerebellum to other brain structures * Connects medulla to thalamus * Homeostatic function (Birthing, heart rate)

Medulla:

Part of the hindbrain "Marrow" * Generally small * Relays information to and from spinal cord * Homeostatic functions (breathing, HR, BP) * Processing of motor and sensory information from the cranial nerves

Preformation VS Epigenesis

Performation: believed that the adult is already present in miniature in one of the gametes (egg or sperm) -Beleived mini adult was always present in cell, and it just got bigger -Precedes cell theory Epigenesis: believed that the embryo generates new complexity and builds its organs as it develops

Presynaptic and Post Synaptic

Presynaptic: in a synapse, of or pertaining to the neuron that sends the signal *Postsynaptic : In a synapse, of or pertaining to the neuron that bears receptors to receive the signal

Motor Cortex Plasticity

Primary motor cortex exhibits learning-related plasticity Motor maps: movements are represented in a map-like fashion across a brain region, such that adjacent neurons are involved in similar movements Learning a skilled motor task leads to an expansion of the cortical involved in controlling the learned movements (Come from strengthening of synapse) Practice makes plastic (practice leads to cortical representation expansion)

Cerebellar Circuitry/LTD

Purkinje cells recieve excitatory input from granule cells and climbing fibers 1a. Climbing fiber fires action potential -> releases glutamate = strong depolarization 2a. Purkinje cell fires an action potential 1b. Purkinje cell: Parallel fiber synapses is weak (action potential -> releases glutamate = weak depolarization) 2b. Purkinje cell fires an action potential only when parallel fibers activated at once Long Term Depression Process 1. Postsynaptic depolarization from climbing fiber activation causes Ca2+ influx through NMDA receptors at the climbing fiber (CF) synapse 2. Glutamate binds to metabotropic receptors at the Parallel Fiber/PC synapse 3. The G protein activates the phospholipase C which produces inositol triphosphate (Ip3) in the cytosol 4.IP3 binds to IP3-gated Ca2+channels on the endoplasmic reticulum, leading to the efflux of Ca2+ into intracellular space (ER stores calcium) 5. Sharp rise in Ca2+ triggers activation of the enzyme protein Kinase C (PKC) 6. PKC pjosphoroylates AMPA receptors, promoting their disassociation and subsequent internalization ( less responsive to glutamate) END RESULT: With the loss of AMPA receptors, the postsynaptic Purkinje cell response to glutamate release from parallel fibers is depressed

Ionotropic Receptors

Resemble ion channels, with a central pore through which ions can flow *Open when activated by a specific neurotransmitter (or other ligand) *3 types: K, AMPA, NMDA Ions flow through their central pore when a neurotransmitter (e.g. a ligand) is bound to them Effect may be excitatory or inhibitory Occur quickly, last only a short time K has limited distribution (allows flow of potassium), mostly AMPA (Allows flow of sodium) in brain. Both are actvuated by neurotransmitter glutamate. Channels formed by K and AMPA allow potassium and sometimes sodium. THEY DO NOT LET CALCIUM FLOW THROUGH NMDA binds glutamate/ can be opened by glutamate or artificial compound (NMDA). It can let significant amounts of calcium flow thorugh in addition to potassium and sodium

Sodium and Potassium in: Resting Phase Rising Phase (Action potential happens here) Falling Phase Return to Resting

Resting Phase: K+ in and out, membrane impermeable to sodium (-70) Rising Phase: Depolarization (Little K+ going out, sodium rushes in) (Action potential happens here) Falling Phase: Repolarization/Hyperpolarization -K+ rushing out, membrane impermeable to Na+ - (-75mV) Return to Resting: -70mV

Resting State

Resting state: -70 mv (-70 less than charge of extracellular fluid) Most cells like to be more negative than outside environment K+ going in and out, sodium can't enter

_________ release onto siphon sensory neurons ultimately leads to increased glutamate release onto the motor neurons

Serotonin release onto siphon sensory neurons ultimately leads to increased glutamate release onto the motor neurons

Dendritic Spines

Small, mushroom shaped protrusions on dendrties Discovered by Cajal Spine Turnover: The idea that dendritic spines may disappear and form anew (ie, are not stable) even in adult brains Dendrites recieve = Post synaptic *Like dendritic spines, axons are also highly dynamic*Axons can sprout new branches, even in intact, adult brains

Spatial and Temporal Summation

Spatial summation of EPSPs is the additive effect (distal synapses activated at different locations but at same time) *Synaptic potentials generated in different parts of a neuron will be additive in their overall effect Temporal summation of EPSPs is the additive effect produced by many EPSPs that have been generated at the same synapse by a series of high-frequency action potentials on the presynaptic neuron. (Overlap) *Synaptic potentials that overlap in time will be additive in their overall effect

Rostrocaudal Patterning

Spinal cord develops from the caudal portion of neural tube, whereas brain develops from the rostral Forebrain (Most rostral)(prosencephalon) Midbrain (mesencephalon) Hindbrain (rhombencephalon), Spinal cord (most caudal) Involves molecular signals that increase in concentration as you go from rostral to caudal along the tube *Caudalize : to change the developmental trajectory of cells so that they will adopt a more caudal (posterior) cell fate *Retinoic acid: The higher the concentration of RA, the more caudal the brain region's fate will be Predicted embryo with increased RA concentration = no forebrain, decreased = no spinal cord *The "default mode" of ectodermal cells is not just to become neural tissue, but actually to become rostral neural tissue.

Presynaptic Specialization

Synaptic Vesicles: Membranous vesicles filled with neurotransmitter molecules, located inside the presynaptic component of a chemical synapse (Store neurotransmitters until use) *glutamate (Excitatory neurotransmitter) Voltage gated calcium: A Ca2+ channel that greatly increases its probability of being open when the cell is depolarized above a threshold value *Selectively premeable to Ca2+ ions 1. Action potential arrives at axon terminal (depolarizes membrane 2.Voltage gated Ca2+channels open and Ca2+ enters the axon terminal 3.Ca2+ entry causes neurotransmitter- containing synaptic vesicles to release their contents by exocytosis (initiates signaling cascade)(Exocytosis = fusion and release)

Role of NMDA Receptor How does opening of NMDA channel lead to increased strength?

Synaptic potentiation is accomplished by changes in the postsynaptic cell (strength comes from more receptors) *NOT caused by increased presynaptic transmitter release Increase in postsynaptic calcium leads to insertion of additional AMPA receptors leads to strengthening of synapse Presynaptic changes in non-mammals (more glutamate released), post synaptic changes in mammals How does opening of NMDA channel lead to increased strength? High levels of Ca2+ binding to calmodulin Activates CAMK11 kinase, that adds more AMPA that glutamate can bind to and also increases rate that neurons can fly in

short term sensitization

Synaptic transmission starts with action potential: Tail shock! 1. Serotonin released from the presynaptic terminal of the interneuron -Serotonin in synaptic cleft binds to metabotropic receptor: Triggers intracellular signaling cascade 2. The serotonin binds to G- protein coupled receptors on the sensory neuron. (G protein breaks off and activates enzyme (Adenylate cyclase) 3. Activation of these metabotropic serotonin receptors activates the enzymeAdenylate cyclase, which synthesizes cyclic adenosine monophosphate (cAMP, the secondary messenger) 3. Increased cAMP levels activate protein kinase A (PKA) 4.PKA phosphorolates (mechanism that can alter activating of protein) voltage gated k+ channels (forces them to close). When clossd, we aren't repolarizing, broadening action potential (slows down ropolarization) Then, PKA leads to openign of more voltage gated Calcium channels (Influx of Ca2+ Ca2+ mobilizes vesicles for exocytosis (more calcium rushes into axon terminal = more vesicles to presynaptic vessicles, more neurotransmitter into cleft to bind to receptors = grater response =Greater withdrawal of gill) High levels of PKA in cytosol cause it to phosphorolate (add phosphate group) Activation of Serotonin pathway by tail stimulation causes increased neurotransmitter release, resulting in a larger EPSP When K+ channels are open, K+ leaves to depolarize *Short-term sensitization will fairly quickly disappear when tail stimulation ceases

Quantal Transmission: Amplitude of EPSE is directly proportional to the number of:

Synaptic vesicles released (2 synaptic vesicles release = 2X EPSE) EPSP amplitude tends to be an multiple of the depolarization caused by a single synaptic vesicle*Paul Fatt & Bernard Katz, 1952 *Quantal nature of synaptic transmission* Quantal Varying in discrete steps rather than continuously

Telencephalon Nuclei

Telencephalon (larger of two divisions of forebrain) nuclei divided into Pallidum, striatum, amygdala, and septum Palladium: Part of basal ganglia Striatum: Motor and action planning Septum: Freezing out fear/aggression Amygdala: Regulating fear

Selective Permeability

The ability of a membrane to allow some ions or small molecules to pass into or out of the cell regularly, while restricting the passage of others * The resting neural membrane is slightly permeable to K+ ions but almost completely impermeable to other ions (Na+) Leak Channel: Tend to be open near resting potential & allows K+ to "leak" out of a neuron at rest (K+ moving down concentration gradient)

Ion basis of the resting potential

The axon's intracellular fluid differs from the extracellular fluid in terms of ion composition *Ion : An atom or molecule with a net positive or negative electrical charge (e.g. Sodium (Na+) or Potassium (K+) ions) Changing the relative concentration of an ion across the membrane can affect this resting potential *High concentration of potassium ions in vs. out (20:1) *Low concentration of Sodium ions in vs. out (9:1) More potassium inside, more sodium outside Ion pump: Active transport of ions across membrane Transporting ions requires ATP Na+/K+ ATPase: An enzyme that moves K+ in and Na+ out of a cell 2 K+ in and 3 Na+ out for every 1 molecule of ATP

Repolarization and Hyperpolarization

The process that brings the membrane potential back towards its resting value after a strong depolarization *Slow opening of voltage-gated K+ channels (and rapid closure of Na+channels/ Na+ already snapped shut) K+ out, membrane at -50--5- mV Hyperpolarization: opposite of depolarization -75 mV (overshot goal) Change in the cell's membrane potential to below the resting potential *K+ channels close & membrane resting potential is restored -Can't fire action potential (Refractory/ relaxation period) -Too much K+ leaks out b/c membrane closes slowly

Plasticity

The quality of being shaped or molded Connections between neurons can and does change with experience we don't have a whole lot of new neurons after birth "One can admit as highly probable that mental exercise promotes in the most involved areas a greater development of [dendrites and axon collaterals]" ~Ramón y Cajal, 1894 Not proven until 20th century Most of what we know about synaptic plasticity aplasia Californica

Synaptic Transmission

The relaying of information across the synapse Discovery: Otto Loewi (1873-1961)*Most known for his famed experiment in 1921*Vagusstoff (vagal substance) = acetylcholine *He stimulated vagus nerve on donor, slowed heart rate, removed fluid sample, added fluid to recipient heart, and saw heart rate slow Started Soups VS Sparks debate (Bullock) How do neurons communicate *Soups: Chemicals released by neurons (neurotransmitter) *Sparks = Electrical signals Both were right First step once action potential arrives at action terminal: Calcium voltage gated channels open

The size of a recorded EPSPdepends on the distance from:

The size of a recorded EPSPdepends on the distance from the axon hillock *EPSPs caused by synapses close to the cell body (proximal synapses) tend to generate more depolarization at the axon hillock than do synapses far out on the dendritic tree (distal synapses)

Three factors can induce an ion to cross a membrane:

Three factors can induce an ion to cross a membrane: 1. The action of an ion pump 2. A difference in concentration of the ions on two sides of the membrane (+ selective permeability) 3. An electrical potential difference across the membrane

Toxins

Toxins that interfere with chemical transmission: Botox Inhibits release of acetylcholine at neuromscular junction (so we cant have muscle contractions) Inhibits the release of acetylcholine at the neuromuscular junction by interfering with SNARE proteins Tetanus: Gaba is bodies main relaxing neurotransmittor Also interferes with SNARE; stops neurons from releasing GABA *Snake Venom: Can act as both presynaptic and postsynaptic neurotoxins: paralysis, weakness, no EPSP, no muscle contraction

NMDA Receptors (Type of Ionotropic Receptor)

When glutamate binds to the extracellular domain, the NMDA receptor changes shape to widen its central pore through which ion may flow NMDA binds glutamate/ can be opened by glutamate or artificial compound. It can let significant amounts of calcium flow thorugh in addition to potassium and sodium Opening also requires strong depolarization *Current flows ONLY when glutamate is bound and the postsynaptic membrane is already depolarized to levels well above the cell's resting potential Both ligand and voltage gated Needs both at once or ions won't flow through Underlies synaptic plasticity in mammals

Nucleus

When talking about a cell, organelle present in eukaryotic cells, bound by double membrane, contains genetic material Brain Nuclei: Fundamental units of brain structure and function (Straitum is an example) Neurons within Brain nucleus have a unique set of connections and physiological propertiesCell bodies with similar features tend to cluster together = brain nuclei (not the same thing as cell nucleus)

Gastrula

Zygote (fertilized egg) becomes blastocyst (a stage of embryonic development when the embryo consists of a hollow (fluid-filled) ball of cells) becomes gastrula (an embryo at the stage following the blastocyst, when it is a hollow cup-shaped structure having three layers of cells) Gastrula divided into ectoderm, Mesoderm and endoderm Ectoderm: First to form, ultimately becomes brain, differentiates into skin and nervous system Top part) Mesoderm: Muscle, bone, and cartilage Endoderm: Lining of gut and lungs

Diencephalon

a division of the forebrain made up of the hypothalamus, prepotic area, retina, and the thalamus Smaller than telencephalon

Exocytosis

a form of active transport in which a cell transports molecules out of the cell 1. Synaptic vesicle moves to the presynaptic membrane 2. Fusion of the vesicular membrane 2b. Membranes are drawn together via protein complexes called SNARES 3.Releases snare proteins into the synaptic cleft 4. Neurotransmitters diffuse across the synaptic cleft and bind to the receptor protein on the post-synaptic membrane 5. Binding of neurotransmitter opens ligand-gated ionchannels, resulting in a graded potential Ligand gated ion channel: Opens to allow ions (e.g. Na+, K+, Ca2+) to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter

Ion Channel

a pore-forming membrane protein that allow ions to pass through the channel pore *Found within the membrane of all excitable cells *Voltage gated Ion channel : ion channels that change their structure in response to voltage changes

EPSP

a postsynaptic potential that makes the postsynaptic neuron MORE likely to fire an action potential Cell less polarized Generates EPSP Depolarization Negative internal charge of the cell becomes briefly positive Example: Acetylcholine at the neuromuscular junction Depolarization (EPSP) increase probability that postsynaptic neuron will fire on action potential Opens, Na+ enters, depolarizes neuron/making it more positive

Electrical Synapse

electrical synapse = mechanical and electrically conductive link between two cells that is formed by a narrow gap (Aka gap junction (3.5nm compared with 20-40nm chemical synapse) Neuron to neuron or neuron to muscle cell Gap junction funnels are composed of pair of hydrophilic channels called connexions (Made up of 6 connexens) (one contributed by each cell at synapse) Ion current flows over a gap junction between neurons (can be bi-directional) Advantage: Speed and precision First example: Otto Loewi showed that acetylcholine could mimic the effect of vagal nerve stimulation * Ed Furshpan & David Potter found evidence for sparks(1959)* Delay between crayfish neurons almost instantaneous -Ink release in sea hare -In thalamus because they synchronize (disruption = seizures), also in our hearts Pros and Cons Synaptic Transmission without delay *ie, defensive reflexes*Synchronize electrical activity of cells *Electrical transmission is less likely to fail *However, they lack gain *Response is the same as the source (Chemical can have summation/additive effects) -Less likely to be blocked -Fewer steps to interfere with

Hypothalamus

part of the diencephalon (forebrain) Homeostaticbehaviors * Regulates pituitary gland: production of hormones & endocrine system * Expression of emotions

Chemical Synapse

specialized junctions through which cells signal to one another via chemical diffusion *Converts an electrical signal (action potential) into a chemical one (neurotransmitter) *Synaptic cleft: the space between neurons across which a nerve impulse is transmitted by a neurotransmitter

Neurulation

the folding process in vertebrate embryos, which includes the transformation of the neural plate into the neural tube After the ectoderm is divided into neural and skin-forming portions, the nervous system is now a flat sheet of cells *Neural Plate: an early stage of neural development when the prospective nervous system is still a flat sheet 1. Neuroectodermal tissues differentiate from the ectoderm and form the neural plate flanked on either side by Neural crest cells (flat sheet) 2. The right edges of the neural plate lift up, transforming the plateinto a neural groove 3. Future skin cells proliferate and push the groove edges towards the midline until they meet 4. Adhesion molecules unique to groove cells make them stick together, causing the neural groove to close (but not stick to skin cells) 5. The neural groove becomes a neural tube that is separate from and coveredbytheskin 6. The closure of the neural tube disconnects the neural crest from the epidermis The neural crest gives rise to some parts of the peripheral nervous sytem The neural tube foes on to form the entire CNS including brain and spinal cord Incomplete closure of neural tube = spina bifida

Graded Potential/ Action Potential Threshold

the strength of the current pulses can vary, leading to different degrees of depolarization with different outcomes SLOW opening of K+ channels, which results in repolarization Action potential threshold: The membrane potential at which enough voltage-gated Na+channels open and, consequently, the action potential is triggered