NEUR 101 Exam 1 (Ch. 1-4)
ion channels
-K+ ions can pass through the selectivity filter. -Other ions do not fit as well and thus do not pass the selectivity filter.
the squid giant axon
-Most mammalian axons are 1-20 μm in diameter. -The North Atlantic squid has giant axons up to 1000 μm (1 mm) in diameter
Luigi Galvani (18th century):
-discovered that a dissected frog's leg will twitch when stimulated with an electrical current -first evidence that nervous signals are electrical
parasympathetic
Preganglionic neurons found in brain and sacral spinal cord (i.e. above and below sympathetic). • Preganglionic neurons are long and dispersed through the body. • Postganglionic neurons are short and use acetylcholine. • decreases heart rate • stimulates digestion • relaxes blood vessels • constricts • prepares body for REST
sympathetic
Preganglionic neurons only found in thoracic and lumbar spinal cord. • Preganglionic neurons are short and collect in the sympathetic chain. • Postganglionic neurons are long and use noradrenaline. • Heart: increases heart rate • GI tract: inhibits digestion • Blood vessels: constricts leading to blood pressure • Lungs: relaxes • prepares body for ACTION
the brainstem: hindbrain, midbrain, and diencephalon
Receives input from all the body's senses. -Sends input to the spinal cord to control most of the body's movements. The brainstem creates a sensory world and directs movement; some animals (e.g. frogs) get by on just a brainstem.
neurotransmitter criteria
Substance exists in presynaptic axon terminal. • Presynaptic cell contains appropriate enzymes for synthesizing the substance. • Substance is released in significant quantities when a nerve impulse reaches the terminals. • Specific receptors that recognize the released substance exist on the postsynaptic membrane. • Experimental application of the substance produces changes in postsynaptic cells. • Blocking release of the substance prevents presynaptic nerve impulses from altering the activity of the postsynaptic cell
midbrain
Tectum: the roof of the midbrain a) Superior colliculi: receives visual information b) Inferior colliculi: receives auditory information Both are involved in producing orienting movements in response to sensory inputs. • The tegmentum: portion of the midbrain below the tectum; several nuclei largely with movement-related functions a) Substantia Nigra: - part of basal ganglia (connected with forebrain) - dopamine cell bodies - degeneration of these neurons seen in Parkinsons disease b) Red Nucleus: - motor center - projects to motoneurons in the spinal cord - Controls limb movements c) Reticular formation (latin reticulum = little net, network) - Sleep and arousal, motor control (muscle tone), temperature regulation, and motor control - extends caudally into the hindbrain d) Periaqueductal gray (mostly cell bodies, i.e. gray matter) - surrounds the cerebral aqueduct - active and passive emotional coping strategies - Species-typical behavior (female sexual behaviors) - opioid analgesia
excitatory and inhibitory synapses
The nature of the postsynaptic receptors determines whether a synapse is excitatory or inhibitory. The same transmitter can be both excitatory and inhibitory depending on the type of postsynaptic receptor.
neurotransmitter
a chemical in the presynaptic axon terminal (stored in synaptic vesicles) that serves as the basis for synaptic communication between neurons.
each spinal segment corresponds to
a region of body surface: cervical, thoracic, lumbar, sacral
Two families of acetylcholine receptors
a) Muscarinic ACh receptors: - slow, metabotropic - 5 subtypes: m1-m5 - widely distributed in the brain, cardiac muscles of the heart, and smooth muscles associated with many organs. - activated by muscarine (agonist; found in Amanita muscaria mushroom). - atropine (Atropa belladonna) and scopolamine block muscarinic receptors (antagonists). b) Nicotinic ACh receptors: - fast, ionotropic (with subtypes) - found on striated muscles and in the brain - activated by nicotine - the active ingredient in tobacco (agonist) - D-tubocurarine (curare) blocks nicotinic receptors at neuromuscular junction causing paralysis.
2 families of noradrenergic receptors: all G-protein coupled
a) a-adrenergic receptors: a1 and a2 b) b-adrenergic receptors: b1 and b2 β1 and β2 excitatory α1 excitatory α2 inhibitory
relating brain and behavior - 3 approaches
a) manipulating the body may affect behavior b) experience affects the body (including the brain) c) body and behavioral measures covary
basal ganglia damage
abnormal movements (parkinson's and huntington's disease) important for motor function stimulus- response or habit learning
2 families of dopamine receptors
all are G-protein coupled a) D1-like family: D1 and D5 receptors - excitatory, stimulate 2nd messenger b) D2-like family: D2, D3, & D4 - inhibitory, inhibit 2nd messenger - typical antipsychotic drugs (neuroleptics) act as antagonists at D2 receptors (e.g. haloperidol).
ion
an atom or a molecule that has acquired an electric charge by gaining or losing one or more electrons; ions are dissolved in fluid.
hyperpolarization
an increase in the membrane potential of a cell, relative to the normal resting potential the persistence of the outward K+ current for a few milliseconds after generating the action potential generates a hyperpolarization. The membrane is unresponsive to further stimuli
VUS score
assesses visual hallucinatory phenomena, visual illusions, and other perceptual changes
locus coeruleus and vigilance
aston-jones and bloom, 1981: Record form LC noradrenergic neurons in freely-moving rats. • Low rates of firing when the rats sleep. • High rates of firing in response novel sensory stimuli. Berridge et al., 2003: • Microinjections of phenylephrin (Phen; α1 agonist) or isoproternol (Iso; β agonist) into the medial septal area. • Medial septal area believed to be important for the arousing effects of NE, and each drug increases the amount of time spent awake.
neurotransmitters were first identified...
at the neuromuscular junction in PNS (acetylcholine)
autonomic nervous system
autonomic = independent, involuntary ganglia = collections of neurons outside the CNS preganglionic and postganglionic cells. 3 parts of the autonomic nervous system a) sympathetic NS b) parasympathetic NS c) enteric nervous system: digestive functioning; innervated by both sympathetic and parasympathetic neurons.
peripheral nervous system
autonomic nervous system: sympathetic , parasympathetic, enteric somatic nervous system: cranial nerves (12 pairs), spinal nerves (31 pairs)
the axon
axon hillock region, afferents arive vs efferents exit
regions of the cortex communicate with one another via
axon tracts
basic premise
bodily processes, particularly those of the nervous system, are the basis of all behavior
central nervous system
brain and spinal cord
the neuron
building block of the nervous system
the neuron
building blocks of the nervous system
butterfly shaped inner portion consists of
cell bodies (gray matter)
two divisions of the nervous system
central nervous system and peripheral nervous system
Acetylcholine synthesis
choline comes from the diet and the liver
ChAT identifies...
cholinergic neurons in the brain
acetylcholine from basal forebrain nuclei plays an important role in...
cognitive functioning
CNS
collecting metabolites to identify NT is difficult - microdialysis has made this possible.
cranial nerves
connected directly to the brain. They convey sensory information from the specialized sensory systems of the head and control movements of the muscle systems of the head.
spinal nerves
connected to the spinal cord. They convey sensory information from the body to the brain and motor information from he brain to muscles in the body.
corpus callosum
connects the two hemispheres
depolarization
decrease/loss of a state of polarity; loss or reduction of negative membrane potential
propagation of the action potential
describes the transmission of an action potential down an axon
Gustav Theodore Fritsch and Eduard Hitzig (19th century):
electrical stimulation of the neocortex causes movement in rabbits and dogs (and possibly humans).
dopamine neurons respond to...
environmental cues that predict reward
EAAT
excitatory amino acid transporter
Roberts Bartholow (19th century):
first published report of electrically stimulating the neocortex of his patient, Mary Rafferty
concentration gradient:
force that causes ions to move from areas of high concentration to areas of low concentration.
How does information flow within a neuron?
from the dendrites through the cell body and out the axon
sulci (sing. sulcus)
furrows (cracks)
located next to spinal cord in the sympathetic chain
ganglia
behavioral neuroscientists can use...
glutamate neurotoxicity as a tool
the glympathic system
glymphatic drainage and CSF
pituitary gland
hormones
mice lacking the dopamine transporter show...
hyperlocomotion
the action potential
is a brief, large changes in neuronal polarity. • is triggered at the axon hillock and propagated along the length of the axon.
NMDA receptors play a key role in...
learning and memory
Electrostatic pressure (potential gradient):
like charges repel and opposite charges attract.
neurons and synapses combine to...
make circuits
most common type of neuron
many dendrites & single axon
cation
positively charged ions, e.g. Na+ or K+
are found only in the spinal cord (thoracic and lumbar).
preganglionic cells
Schwann cells
produce myelin in PNS
When the AP arrives at the synapse a chemical called a neurotransmitter is released that affects the resting potential of the postsynaptic membrane...
producing a postsynaptic potential
sherrington (1897)
proposed the term synapse
Loewi's experiment
put fluid in heart and stimulate vagus nerve (slow heart), then transfer fluid to another heart, which then also slowed Identified vagusstoff (ACh) that reduces heart rate and accelerenzstoff (Epinephrine) that increases heart rate
acetylcholine inactivation
removed by acetylcholinterase that is in the postsynaptic membrane
gryi (sing. gyrus)
ridges (bumps)
biological psychology
seeks to explain behavior in terms of underlying physiology
6-hydroxydopamine (6-OHDA) lesions dopamine neurons resulting in...
severe behavioral dysfunction
neurons can be classified by
shape, size, or function
Otto Loewi (1921)
simple but effective experiment proving the existence of neurotransmitter (Vagusstoff - substance from the vagus nerve).
neuroscience involves many levels of analysis
social level: individuals behaving in social interaction organ level: brain, spinal cord, peripheral nerves, and eyes neural systems level: eyes and visual brain regions brain region level: visual cortex circuit level: local neural circuit cellular level: single neuron synaptic level molecular level
neuron structure
soma/cell body, dendrites, axon, axon terminals synaptic buttons
Astrocytes
star-shaped, local blood flow control, works closely with neurons
neuroscience
study of the nervous system
fibers carrying sensory information from the sensory receptors of the body collect together forming
the dorsal root
the neuron doctrine
the idea that individual cells transmit signals in the nervous system, and that these cells are not continuous with other cells as proposed by nerve net theory
the nerve impulse
the moving action potential (1-100 m/s)
neurons differ according to
the neurotransmitters they synthesize and use to communicate with other neurons
psychology
the science that deals with mental processes and behavior
outer portion of spinal cord consists of
tracts (white matter)
behavioral neuroscience seeks to...
understand all these relationships
optogenetics
using light-gated ion channels
fibers leaving the spinal cord carrying motor information to the body from
ventral root
microglial
very small phagocytic glial cell that removes waste products from the central nervous system
different cell populations utilize different...
vesicular glutamate transporters
animal research makes vital contributions to biological psychology
Animals serve as models in which to study brain and behavior relations. The use of animals in research is not a right but a privilege. Federal regulation: - Animal Welfare Act (1966, with several revisions since). - Use of animals in biomedical research is delegated to the Secretary of Health and Human Services, the Director of the National Institutes of Health (NIH) and the Office of Laboratory Animal Welfare (OLAW). Research institutions establish Institutional Animal Care and Use Committees.
Speed of neural transmission - axons, synapses, and postsynaptic receptors
Axons: - Large diameter axons conduct faster than small diameter axons (less resistance to the flow of current). - Myelinated axons conduct faster than unmyelinated axons. Synapses: - chemical synapses are slower than electrical synapses - chemical synapses have a wider synaptic cleft than electrical synapses - delay across the cleft due to presynaptic calcium influx and transmitter diffusing across the cleft Postsynaptic processing (receptors): - ionotropic receptors are ion channels and thus are fast. - metabotropic receptors are G-protein coupled require extra steps
Telencephalon
Basal ganglia: - not a ganglia as in autonomic NS - rather a collection of nuclei (caudate nucleus, putamen, globus pallidus, subthalamic nucleus, substantia nigra (midbrain)) that form a circuit. - Caudate nucleus receives projections from all areas of neocortex and projects through the putamen and globus pallidus to the thalamus and from there to motor cortex areas. - Substantia nigra provides dopaminergic input to to basal ganglia. Limbic system: - Amygdala, hippocampus, fornix, cingulate gyrus (cortex) cingulate gyrus (attention), hypothalamus, mammillary bodies. - James Papez (1937): people with rabies have infections of limbic structures. - Amygdala damage produces changes in emotional behavior. - Limbic structures have a role in emotion but also in memory and motivation.
Norepinepherine (NE)
Cell bodies found in 3 main clusters in the brainstem: a) locus coeruleus: - most important system - descending projections to cerebellum and spinal cord - ascending projections to virtually all parts of the diencephalon and telencephalon b) lateral tegmental system - descending projections to thoracic and upper lumbar spinal cord. This is where the cell bodies of the sympathetic preganglionic neurons are located. c) dorsal medullary group - provides inputs to the cranial parasympathetic system. • PNS: sympathetic NS postganglionic cells use norepinepherine
serotonin (5-hydroxytryptamine, 5-HT)
Cell bodies found in the raphe nuclei in the midbrain and the lower brain stem. • Caudal system (caudal pons and medulla) projections descend to the spinal cord. • Rostral system (rostral pons and midbrain) projections ascend to innervate basal ganglia, limbic system, diencephalon, and cortex. • 2 additional serotonergic projection systems, one to the cerebellum and one to the pons and medulla
dopamine
Cell bodies found in two midbrain areas: a) Substantia Nigra: - project to the striatum (caudate nucleus and putamen, part of basal ganglia system). - termed the mesostriatal (nigrostriatal) dopamine system - important for movement - loss of these neurons implicated in Parkinsons disease - Effects of of MPP (metabolite of MPTP). b) Ventral Tegmental Area: - projects to nucleus accumbens, amygdala, hippocampus, and cortex - termed the mesolimbocortical dopamine system - part of the brains reward system: all drugs of abuse act on this system either directly or indirectly. - excessive dopamine plays a role in schizophrenia. • There is also a small cluster of dopamine neurons in the hypothalamus that give rise to the tuberohypophyseal dopamine pathway - inhibits prolactin release form the pituitary gland.
sodium-potassium exchange pump
In mammalian neurons the overall resting or steady-state membrane potential is approximately -60 to -70 mV (not equal to any single ionic equilibrium potential). • ® ions are constantly moving along their concentration gradients; e.g. K+ would constantly move out of the cell. The problem is solved by active transport of ions against their concentration gradients through specialized pumps called ionic pumps. K+ must be pumped into the cell and Na+ must be pumped out of the cell. The electrogenic sodium-potassium pump is crucial for maintenance of the resting potential. • The pump is electrogenic because every cycle of the pump results in the net outward flow of one positive ion, contributing to the maintenance of negative polarity inside of the neuron (3 Na+ out, 2 K+in). • At rest the membrane permeability to sodium is low, so the pump effectively keeps the intracellular concentration of sodium low. At the same time, by transporting potassium into the cell, the pump keeps the intracellular concentration of potassium high.
two families of postsynaptic receptors
Ionotropic Receptors: ligand-gated ion channels: Ligand binds to receptor which opens ion channel and changes postsynaptic polarity
glutamate receptors are ionotropic or metabotropic
Ionotropic glutamate receptors - AMPA: Na+ - Kainate: Na+ - NMDA: Na+ and Ca2+ Metabotropic glutamate receptors -mGluR1 - mGluR8 -some excitatory -some inhibitory NMDA receptors are unique
post-synaptic receptors are excitatory or inhibitory
Ionotropic receptors: - Some are cation channels (Na+) à excitatory (EPSPs). - Some are anion channels (Cl-) à inhibitory (IPSPs). Metabotropic receptors: - Some activate the cell à excitatory. - Some inhibit the cell à inhibitory.
excitotoxic brain damage and ischemia
Ischemia - an interruption of blood flow to the brain. - Focal ischemia - localized disruption of blood flow (stroke) - Global ischemia - global disruption of blood flow (heart attack) • One consequence of ischemia is a massive release of glutamate in the affected area - NMDA antagonist reduce ischemic cell loss in animal models; side effects in humans lead to limited clinical efficacy. - Drugs affecting the glycine binding site on the NMDA receptor show promise in animal models of focal ischemia (Kelly et al., 2003).
hallucinogenic drugs interact with the serotonergic system
LSD, psilocybin, and 5-Methoxy-DMT are all structurally similar to serotonin. • LSD binds to at least eight serotonergic receptor subtypes. • Serotonergic 5-HT2A receptors particularly relevant for visual hallucinations.
what happens at the synapse - postsynaptically
Lock and key analogy: a ligand (key) is a molecule of correct shape (e.g. a neurotransmitter molecule) that fits into the ligand-binding site (lock) of a receptor protein. • Endogenous ligand: a ligand made inside the body (e.g. neurotransmitters and hormones) • Exogenous ligand: a ligand not made inside the body (e.g. drugs and toxins)
high levels of glutamate can be toxic to nerve cells
Lucas and Newhouse (1957): subcutaneous injection of MSG (the sodium salt of glutamic acid) causes retinal damage in mice. • Olney (1969): intracranial MSG (arcuate nucleus of the hypothalamus) causes brain damage in mice.
GABA and Epilepsy
Measuring GABA levels in epileptic patients - 2 studies have found reduced CSF GABA (one has not) - But, reduced CSF GABA does not appear to be unique to epilepsy • Antiepileptic drugs act on GABA signaling - Though some are also thought to act by inhibiting voltage-gated Na+ and/or Ca2+ channels. • Kindling (Goddard, McIntyre, Leech, 1969) - an animal model of epilepsy - Repeated application of brief tetanic stimulation to a variety of brain areas (limbic system, cortex, basal ganglia) that is too weak to induce seizures. - Cumulative effect over time leading to seizures à repeated stimulation is changing something at the locus of stimulation. - Studies have found GABA abnormalities in the kindled brain.
two families of postsynaptic receptors
Metabotropic receptors: not directly associated with an ion channel. Instead they activate other proteins in the cell membrane (G proteins à G protein coupled receptors). There are many different types of G proteins.
the falling phase of the action potential
Na+ channels are inactivated; outward flow of K+ ions repolarizes the membrane.
cortical layers
Neocortex or isocortex (cortex = latin bark of a tree) - 6 distinct layers of cells (gray matter) - layer 1 has few cell bodies, layer 3 has many cell bodies - white matter below - allocortex - 3 layers - pyramidal cells: most prominent type of neuron - cortical columns: information processing units (Mountcastle: somatosensory cortex; Huebel & Wiesel: occipital cortex)
excitation of VTA dopamine neurons reinforces operant behavior
Photostimulation of VTA dopamine neurons excites VTA dopamine neurons and increases nucleus accumbens dopamine release Photostimulation of VTA dopamine neurons in the VTA reinforces operant behavior
brain is well protected with
3 layers of meninges: a) dura mater (hard mother), outermost layer b) arachnoid (web between), middle layer c) pia mater (tender mother), innermost layer space between layers is filled with cerebrospinal fluid (CSF) meningitis=inflammation of the meninges
biological psychology = physiological psychology = behavioral neuroscience
-
blood supply to the brain
- 2 carotid arteries give rise to anterior and middle cerebral arteries. These innervate anterior and middle portions of cortex, respectively. - 2 vertebral arteries fuse to form basilar artery. It supplies the brainstem and posterior cortex. - Circle of Willis: backup system - Stroke: blockage of blood supply to a brain area.
families of 5-HT receptors
5-HT1 and 5-HT2 receptors - metabotropic • 5-HT3 ionotropic, excitatory • 5-HT4 - 5-HT7 - metabotropic • Raphe nuclei cells fire most during wakefulness when aroused and active (like NE). • Together with the locus coeruleus, the raphe nuclei are part of the reticular activating system: brainstem neurons arouse and awaken the forebrain. • 5-HT is also implicated in the control of mood and emotional behaviors - SSRIs, e.g. Prozac.
glutamate synthesis
1. Glucose -‐-‐> Acetyl CoA -‐-‐> α-‐ketoglutarate via glycolysis and TCA cycle, respectively 2. α-ketoglutarate --> glutamate via transamination
the brain is
1400 g (2% of body weight) consumes 20% of bodies energy
the refractory period
2 phases of the refractory period: a) absolute refractory period: immediately following the AP, no amount of stimulation can induce another AP b) relative refractory period: only very strong stimulation can induce another AP Both phases are related to changes in membrane permeability to Na+ and K+: Na+ channels are completely open during the rising phase ® further stimulation has no effect Na+ channels close during the falling phase and do not open again for a period of time. Voltage-gated K+ channels are open during falling phase and the neuron becomes hyperpolarized ® stronger depolarizing current is required to induce an AP
neurons vs glial cells
200 different types of neurons vs 4 types of glial cells
antiepileptic drugs acting on the GABA system
Benzodiazepines and Phenobarbital enhance GABAA signaling. Tiagabine (Gabitril) elevates synaptic GABA by blocking GABA uptake. Vigabatrin (Sabril) inhibits GABA-T, producing increase GABA levels.
acetylcholine is the target of many naturally occurring and man-made toxins
Botulinum Toxin produced by the bacterium Clostridium botulinum - Bacteria grows in anaerobic environments (sealed food cans). - Toxins selectively taken up by cholinergic neurons that innervate muscles. - Toxins interfere with the release of ACh at the neuromuscular junction. - Weakness, paralysis, blurred vision, difficulty speaking and swallowing, GI distress. • Nerve gases (Sarin and Soman) - Irreversible AChE inhibitors. - Rapid accumulation of ACh at synapses throughout the CNS and PNS. - Overstimulation of ACh synapses. - Profuse sweating and salivation, vomiting, convulsing, asphyxiation.
dendrites
Branchlike parts of a neuron that are specialized to receive information.
what happens at the synapse - presynaptically
Ca2+ influx into the presynaptic terminal is a critical step in neurotransmitter release. - upon entry, Ca2+ binds to a protein called calmodulin - Ca2+/calmodulin complex binds to vesicle membrane - Vesicles bind to presynaptic membrane (SNARE proteins and synaptotagmin) - Exocytosis.
Catecholamines
Catecholamine refers to organic compounds that contain a catechol nucleus and an amine group - Dopamine - Norepinepherine (aka noradrenalin) - Epinepherine (aka adrenalin)
the ventricular system
Cavities filled with CSF. • CSF formed by choroid plexus in the lateral ventricle. • lateral, third, and fourth ventricle. • CSF acts as a shock absorber and carries various materials including nutrients. • Ventricles are enlarged in some diseases (e.g. schizophrenia).
cytoarchitectonic maps
Constructed by examining the neurons of the neocortex to identify regions that have unique organization. • Sensory areas: many layer 4 cells, which receives axons from other areas. • Motor areas: many layer 5 and 6 cells, which send axons to other areas. • Association areas: many layer 1, 2, 3 cells, which receive input mainly from layer 4. • Brodmann's map: Widely used cytoarchitectonic map
hindbrain
Control various motor functions ranging from breathing to balance to fine movements. • Metencephalon: a) Cerebellum ( little brain) - deep cerebellar nuclei covered by three layered cerebellar cortex - Purkinje cells (fan shaped dendrites) - middle - granule cells - bottom; axons project to top layer - parallel fibers - top layer b) Pons (bridge between cerebellum and the rest of the brain) - - many axons pass from left to right hemispheres in the pons - motor and sensory control nuclei (cranial nerves) Myelencephalon - the medulla oblongata - continuous with spinal cord - controls breathing and heart rate (damage often fatal) - cranial nerves XI and XII (neck and tongue muscles)
the action of synaptic transmitters is stopped rapidly
Degradation: enzymes break down transmitter and components are recycled. e.g. acetylcholine: acetylcholinesterase breaks down ACh into choline and acetic acid Reuptake: active re-uptake of of transmitter through transporters located presynaptically. e.g. monoamine neurotransmitters have specialized transporters.
how do sensory stimuli produce action potentials? (example of tactile stimulation)
Dendrite of sensory neuron is wrapped around the hair. Displacement of the hair causes stretch-sensitive channels on the dendrites to open, allowing Na+ influx. "mechanical" Na+ influx causes voltage-gated Na+ channels to open.
integrating synaptic inputs - temporal summation
If stimuli are given in rapid succession then potentials also add or subtract. The closer in time two inputs occur, the greater their overlap, and the more complete their summation.
Monoamine Inactivation
Each has a pre-synaptic transporters: DAT, NET, SERT. • Catecholamines and indoleamines are broken down by enzymes: monoamine oxidases (MAOs) and catechol-Omethyltransferase (COMT). • MAOIs used as antidepressants.
Maintenance of resting potential
Each ionic species has its own equilibrium potential, so the overall resting membrane potential must be influenced by all of these. • The Goldman-Hodgkin-Katz equation describes the resting membrane potential for a given set of concentrations inside and outside of the cell and the relative permeability of the membrane to each of these ions:
two types of postsynaptic potentials
Excitatory postsynaptic potentials (EPSP): a small depolarization of the postsynaptic cell Inhibitory postsynaptic potential (IPSP): a small hyperpolarization of the postsynaptic cell usually due to opening of Cl- channels.
Oligondendrocytes
Form myelin sheath in CNS
studying ion channels
Patch clamp recordings (Neher & Sakmann): -Tiny glass pipette (~1μm) sealed to membrane -Slight suction clamps a 'patch' of membrane containing individual ion channels - currents across the patch of membrane can be recorded
GABA receptors are inhibitory
GABA: ionotropic (Cl- channels) - Muscimol: classic GABAA agonist (Amanita muscaria) -Rudgley (1999) - various Siberian peoples have the custom of eating Amanita muscaria seeking its hallucinogenic properties (macroscopia) Bicuculline: GABAA competitive antagonist with potent convulsant effects. Benzodiazepines (e.g. valium) modulate GABAA signaling. 2) GABAB: metabotropic 3) GABAC: ionotropic (Cl- channels) The GABAA receptor has 5 subunits
Peptide Neurotransmitters
Opioid Peptides (compounds that act as agonists at opioid receptor types mu, delta, & kappa) - Endorphins: b-endorphin - Enkephalins: met-enkephalin and leu-enkephalin - Dynorphins: Dynorphin A and Dynorphin B • Gut-brain peptides (these are found in both the CNS and the gastrointestinal tract) - Choleocystokinin (CCK): releases bile from gallbladder, widespread in the brain (eating behavior). - Neuropeptide Y: control of food intake. - Neurotensin: often co-localized with dopamine. - Substance P • Pituitary hormones and hypothalamic releasing hormones (stimulate pituitary gland; see Chapter 6).
acetylcholine (ACh)
Otto Loewi - Vagus stuff; first NT discovered (neuromuscular junction) • In the CNS cholinergic cell bodies are found in three brain areas: a) pons/tegmentum - pedunculopontine and laterodorsal tegmental nuclei: ascending projections to thalamus, midbrain dopamine neurons. Descending projections to spinal cord and cerebellar nuclei. b) basal forebrain - medial septum, nucleus of diagonal band, nucleus basalis and substantia inominata: projections to hippocampus, amygdala, and cortex. c) cholinergic interneurons in the caudate nucleus and putamen (part of the basal ganglia).
threshold of excitation
Sodium channels open resulting in an inward movement of Na+ ions (voltage-gated Na+ channel).
integrating synaptic inputs - spatial summation
Spatial summation: - each excitatory or inhibitory input causes a local depolarization or hyperpolarization which passively spreads and dissipates with distance. - if the dendrite is stimulated at two points close together, the graded potentials will add (summate). - all inputs, excitatory and inhibitory, are summed across the cell body and dendritic region. - Only if the overall sum is sufficient to depolarize the axon hillock region to threshold is an action potential triggered.
how to study tiny voltage-gated ion channels
Specific toxins to block specific ion channels- a) tetrodotoxin (TTX) and saxitoxin (STX): block sodium channels AP's cannot be produced - TTX found in the organs (especially ovaries) of the puffer fish. - STX found in algae and concentrated by certain shellfish. b) Batrachotoxin forces sodium channels to stay open -synthesized by South American poison arrow frogs c) tetraethylammonium (TEA): blocks potassium channels > blocks hyperpolarization
g protein operate by two major mechanisms
Stimulation or inhibition of ion channels. e.g. K+ channels are stimulated by specific G proteins > K+ flows out of the cell > hyperpolarization. - Second messengers (cyclic AMP, arachidonic acid) one key mechanism in which second messengers work is the activation of protein kinases. Protein kinases are enzymes that phosphorylate other proteins, such as ion channels (might open), enzymes involved in neurotransmitter synthesis, a neurotransmitter receptor (might become more sensitive). Protein kinases can also phosphorylate proteins in the cell nucleus that turn on/off specific genes.
what does GABA do?
Structures possessing GABA projection neurons (globus pallidus, substantia nigra pars reticulata, cortex) tend to chronically restrain areas they project to. • Structures with GABAergic interneurons: GABA inhibits output neurons from the same structure (e.g. GABA and dopamine neurons in the VTA). • GABA hypothesis of epilepsy: - Epilepsy: class of neurological disorders characterized by recurrent seizures - Focal epilepsy: intermittent, high-amplitude electrical discharges at the site of epileptic focus during interictal periods - 2 Phases of discharge: 1) a series of synchronous depolarizations (excitatory input) followed by 2) hyperpolarization (inhibitory input) - Transition to full-blown seizures is thought to involve a decrease in the hyperpolarizing phase, i.e. a failure of inhibition à GABAergic systems may be operating improperly
concentration gradients and potential gradients- the example of K+
The concentration gradient pulls K+ ions out of the cell. The inside will now become more negative, and the potential gradient now pulls K+ ions back into the cell. At a certain membrane potential, the forces exerted by the two gradients will balance each other out. When this occurs it is equally likely for an ion to move out of the cell as it is to move in, and there is no net flow of ions. The ion (K+) is at equilibrium (-102 mV). Equilibrium potentials can be precisely determined for an ion by using the Nernst Equation
diffuse modulatory systems of the brain (ACh, DA, NE, 5-HT)
The core of each system has a relatively small set of neurons. • Neurons of the diffuse systems arise from the core of the brain, most of them from the brainstem. • Each neuron can influence many others, because each has an axon that may contact more than 100 000 postsynaptic neurons spread widely across the brain. • Many of the synapses release transmitter into the extracellular fluid so that molecules can diffuse to many neurons.
the membrane potential
The differential distribution of ions on the inside and outside of the cell results in an electrical potential difference across the cell membrane (~ -50 to -80 mV). The membrane potential can be measured.
the rising phase of the action potential
The inward movement of Na+ opens more Na+ channels, bringing the membrane potential close to ENa (+ 40mV). At the same time, potassium channels open allowing K+ to leave the cell (voltage-gated K+ channels).
the Nernst Equation
This equation was first formulated by Walter Nernst in 1888. z is the valence of the ion, [ion]o and [ion]i refer to ionic concentration outside and inside the cell respectively.
5-HT synthesis
Tryptophan (essential amino acid found in animal and plant protein)->5 Hydroxytryptophan (marker for 5-HT neurons) ->5 Hydroxytryptomine
Catecholamine synthesis
Tyrosine --> L-Dopa --> Dopamine --> Norepinephrine --> Epinephrine
three distinct proteins that package glutamate into vesicles...
VGLUT1, VGLUT2, VGLUT3
VMAT
VMAT: vesicular monoamine transporter packages monoamines into vesicles
anion
negatively charged ions, e.g. Cl
electrical synapses (gap junctions) work with...
no time delay
dopamine mediates approach toward...
novel stimuli and rewards in the environment
forebrain
•Diencephalon : a) Thalamus: larger of the two - sensory weigh station - all sensory information goes to the thalamus (different nuclei for different modalities) - from thalamus sensory information continues to appropriate cortical areas - bidirectional connectivity with the cortex b) Hypothalamus: - under the thalamus - a small but very complex and very important structure - feeding, temperature regulation, reproductive behavior, hormone secretion (via pituitary gland) The telencephalon is the largest region of the mammalian brain (2000 cm2, ~2/3 hidden in folds): - cerebral cortex: regulates mental activities such as perception and planning - basal ganglia: controls voluntary movement - limbic system: regulation of emotion and behavior
