5. Nerve/Synapse Flashcards
Central Nervous System (CNS) components
brain + spinal cord
Peripheral Nervous System (PNS) components
neurons (motor + sensory) and autonomic fibers
motor neurons
efferent fibers that give out information to muscles
sensory neurons
afferent fibers that receive information
autonomic fibers
connect spinal cord to visceral organs
synapse
specialised site of communication between neurons
neuron physical characteristics
- cell body = soma
- branching dendrites
- a single axon
the action potential starts at the… and propagates down the…
initial segment
axon
resting membrane potential
small excess of negatively charged ions inside the membrane of neuron
resting membrane potential =
-70mV
what creates the resting membrane potential?
- concentration gradients for various ions
- selective permeability of membrane to K+ ions
membrane potential at rest:
- neuronal membrane highly permeable to K+ but less permeable to other ions
- K+ leak out of the cell down their concentration gradient
- unpaired (-) ions accumulate inside the cell, creating an electric gradient: K+ ions pulled back into cell
at equilibrium: electrochemical gradient
chemical gradient = electrical gradient
Nernst Equation describes…
the membrane potential at equilibrium
Nernst Equation (E)
61/z * log([ion]o/[ion]i)
main factor determining the neuron resting membrane potential
equilibrium potential for K+
equilibrium potential for K+
-90mV
leak channels
proteins (ion channels) that form K+ selective pores through the membrane, always open
equilibrium potential for Na+
+70mV
equilibrium potential for Cl-
-80mV
why is the resting membrane potential slightly more + than the equilibrium potential for K+?
small inward leak of Na+
sodium-potassium pump
pumps 3 Na out and 2 K in against their concentration gradients by using energy produced by ATP hydrolysis
action potential
brief electrical impulse that travels down the axon
action potential spike/peak
membrane potential approaches Na equilibrium potential but very briefly
depolarisation
when membrane potential peaks at 30mV as sodium channels open
repolarisation
membrane potential returning to its resting potential after having spiked
hyperpolarisation
when membrane potential decreases below its resting potential
when is an action potential initiated?
when the membrane potential depolarises to a threshold level, influenced by voltage-gated sodium channels
can the magnitude of action potential increase/decrease?
no, the action potential is an all or nothing mechanism
3 critical properties of voltage-gated sodium channels
- closed at resting membrane potential: open when repolarising
- selective for Na+
- open channel rapidly inactivates, stopping the flow of Na+ ions
absolute refractory period
sodium channels are inactive and the membrane is completely unexcitable for a few seconds after an action potential
what does speed of propagation depend on?
how fast the Na+ channel can be converted back to its closed configuration after repolarisation
relative refractory period
membrane potential overshoots its resting potential, making the axon less excitable and unlikely to fire an action potential
action potential is a positive or negative feedback mechanism?
positive
action potential steps
- depolarisation of membrane to threshold activates small fraction of sodium channels: Na+ flows in membrane
- inside of neuron gets more positive, further depolarising the membrane: more sodium channels open
- all sodium channels open: peak reached
- sodium channels inactivated
- membrane relaxes back to resting potential
which ion channel is more present in the axon membrane?
voltage-gated sodium channels
what is the dominant permeability at action potential peak?
Na+
rising phase of action potential:
- sodium channels open
- potassium channels still closed
falling phase of action potential
- sodium channels close
- potassium channels open (takes longer)
which ion channels have delayed activation?
voltage-gated potassium channels -> take longer to open
when are potassium channels maximally open?
during repolarisation phase: K+ can flow out faster to bring membrane potential back to -70mV
Action potential propagation steps
- depolarisation: sodium ions flow in
- (+) charge in this region attracted to - charge in adjacent segment
- (+) charge flows into next axon segment
- propagation down axon continuously like a wave
- (+) charge can only move forward due to rapid sodium channel inactivation
how do neurons send information?
through means of frequency and pattern of action potentials
what do neurotoxins target?
sodium channels
tetrodotoxin (TTX)
produced by puffer fish, extremely potent sodium channel inhibitor
batrachotoxin
secreted by frogs, deadly sodium channel activator: irreversibly opens sodium channels so constant AP being fired
drugs that can also block sodium channels
local anesthetics and antiepileptics
local anesthetics
injected into the nerve to block its sodium channels so the pain information will be blocked from going up to the brain at this point
examples of local anesthetics
lidocaine, benzocaine, tetracaine, cocaine
anti epileptics
prophylactic drugs taken everyday to prevent seizures (without putting you to sleep) by blocking sodium channels
anti epileptics examples
phenytoin (Dilantin), carbamazepine (Tegretol)
propagation rate of action potential is proportional to…
axon diameter and myelination
Wider axon propages slower or faster?
faster
How can thinner axons propagate faster?
surrounded by Myelin sheets
Myelin formed by: (2)
- Schwann cells in PNS
- oligodendrocytes in CNS
nodes of Ranvier
periodic gaps in myelin sheets
nodes of Ranvier contain a high concentration of…? why?
voltage-gated sodium channels to enable signal to be regenerated at periodic intervals due to sodium influx
cause of multiple sclerosis
loss of myelin due to immune system attacking myelin made by oligodendrocytes
white matter
regions of the brain and spinal cord containing mostly myelinated axons
grey matter
comprises cell bodies, dendrites and synapses
3 main types of synapses
- axodendritic
- axosomatic
- axoaxonic
axodendritic synapse
between axon and dendrites (most common)
2 types of axodendritic synapses
- spine synapse = mainly excitatory
- shaft synapse = mainly inhibitory
axosomatic synapse
on neuron body (soma)
axoaxonic synapse
axon synapses with the axon of another neuron
presynaptic refers to…
everything upstream a synapse
postsynaptic refers to…
everything downstream a synapse
divergence
a single neuron makes synapses with many other neurons through its branching axon
presynaptic vesicles
contain neurotransmitters
synaptic cleft
narrow space between presynaptic terminal and postsynaptic spine
active zone
vesicles docked to the membrane adjacent to synaptic cleft, ready to be released
postsynaptic density
darker spots on postsynaptic spine, containing proteins for neurotransmitter reception
Calcium concentration inside neuron is very…
low
what triggers neurotransmitter release?
activation of voltage-gated calcium channels
neurotransmitter release steps
- action potential invades presynaptic terminal, depolarising the membrane
- calcium channels open so Ca moves into presynaptic terminal
- synaptic vesicles fuse with presynaptic membrane
- neurotransmitters released into synaptic cleft
- transmitter activates receptors in the postsynaptic membrane, opening ligand-gated ion channels
calcium-dependent fusion of synaptic vesicle at active zone
- action potential activates voltage-gated calcium channels so Ca enters neuron
- calcium binds to receptor on presynaptic terminal
- vesicle fuses with the membrane
- transmitters in vesicles released into synaptic cleft
- membrane reforms
toxins that can act on calcium-dependent fusion of synaptic vesicle at active zone
- tetanus
- black widow spider toxin: too many vesicles fuse with the membrane
- botox: proteins responsible for neurotransmitter reception chewed up
Excitatory Postsynaptic Potential (EPSP)
depolarises the postsynaptic membrane, making it more likely to fire an AP
-> involves excitatory synapse
Inhibitory Postsynaptic Potential (IPSP)
hyperpolarises the postsynaptic membrane, making it less likely to fire an AP
-> involves inhibitory synapse
glutamate
main excitatory neurotransmitter in the brain
ionotropic receptors
ion channels that open in response to binding of neurotransmitters to receptor sites on their external surfaces
2 types of ionotropic glutamate receptors
- AMPA receptors
- NMDA receptors
–> ligand-gated ion channels
receptors involved in excitatory transmission
- AMPA receptors
- NMDA receptors
AMPA receptors
responsible for fast EPSP at excitatory synapse
AMPA receptor activation
- Glu released from vesicles and diffuse across synaptic cleft
- Glu bind to AMPA receptors, opening its ion channel
- AMPA is permeable to sodium so Na+ flows into postsynaptic spine, depolarising the post-synaptic cell
NMDA receptors
have their pore blocked by Mg2+ at resting membrane potential so they can’t conduct current
NMDA receptor activation
- depolarisation expels Mg2+ so pore can conduct
- open pore is highly permeable to Ca2+ and noncovalent cations: Calcium flows into neuron
2 conditions required for NMDA receptor activation
glutamate binding and postsynaptic depolarisation
synaptic plasticity
idea that synapses can change and become stronger (larger EPSP)
Long-Term Potentiation (LTP)
model of synaptic plasticity in experimental context
3 phases of LTP
- Control: a single action potential stimulates Glu release
- Induction: high frequency action potentials depolarise post-synaptic cleft so Calcium can be conducted, leading to more Glu release
- LTP: hours after induction, a single action potential triggers a bigger/stronger EPSP
excitotoxicity
high concentrations of glutamate are toxic to neurons
how is excitotoxicty likely to contribute to neuronal degeneration after a stroke?
- stroke: neurons die, releasing Glu which diffuses to surrounding regions
- over activation of AMPA and NMDA receptors causes too much Calcium to flow into the cell
- cell apoptis/suicide
2 broad functions of inhibitory synapses
- act as a break on excitatory neurons
- shape the pattern of excitatory neuron’s action potential
which type of synapse is more local?
inhibitory synapses
Y-aminobutyric acid (GABA)
main inhibitory neurotransmitter in the brain
GABA A receptor
postsynaptic ionotropic receptor responsible for IPSP
GABA A receptor activation
- GABA binds to GABA A receptors, activating it
- Influx of Cl- into cell hyperpolarises postsynaptic membrane
drugs that can act on GABA A receptors
- xanax makes GABA A receptors stay open longer, accentuating the IPSP and making you sleepy
- ethanol makes GABA A receptors more receptive, causing more inhibition in the brain, making you sleepy
synaptic integration key points (5)
- excitatory inputs usually located on dendritic spines
- inhibitory inputs usually clustered on/near cell soma
- action potential fired depending on relative balance of EPSPs and IPSPs
- each neuron is either excitatory or inhibitory
- inhibitory neuron can only inhibit other neurons by having excitatory inputs to fire action potentials
Metabotropic receptors (GPCRs)
- aka G-Protein Couple Receptors
- found at synapses but aren’t ion channels
GPCR activation
- Glu release in synaptic cleft
- Glu binds to mGluRs (metabotropic Glu receptors), inducing a conformational change, activating mGluRs
- 2nd messenger generated by mGluR inside postsynaptic spine
- 2nd messenger diffuse inside cell, activating a range of cellular proteins
what does 2nd messenger activate when metabotropic receptors activate?
- ion channels: 2nd messenger binds to it on inside of cell, causing it to open
- protein kinases: proteins that add phosphates to another protein to activate it
- transcription factors which will regulate gene expression in the nucleus: gene transcription + protein synthesis
Glutamate and GABA activate what kind(s) of receptors?
both ionotropic and metabotropic receptors
neuromodulators
substances that aren’t directly involved in fast flow of neuronal information but modulate global neural states, influencing alertness, attention and mood
neuromodulators interact mainly with which kind(s) of receptors
metabotropic receptors
neuromodulators examples
- dopamine
- serotonin
- norepinephrine
- endorphins (neuropeptide)
where do neuromodulators originate from?
tiny clusters of neurons in small brainstem or midbrain nuclei
how are neuromodulators spread out?
neuron’s axon in brainstem extend all the way up to cerebral cortex
dopamine involved in…
- addictive behaviours
- connections between + emotion and associate behaviour: reward pathway
serotonin influences…
mood
antidepressant effect on neuromodulators
affect serotonergic transmission
-> ie Prozac
simulants effect on neuromodulators
affect dopamine and norepinephrine transmission
-> ie amphetamines, cocaine
