Week 1 - Synaptic Transmission Flashcards
criteria for chemical neurotransmitters
- present in presynaptic terminal
- released in response to stimulation; release must be Ca++ dependent
- specific receptors for neurotransmitter must be present on postsynaptic cell
- mechanism to inactivate neurotransmitter must be present (reuptake, enzymatic breakdown)
how are synaptic networks dispersed?
- spatially focused, subserving behaviors requiring precise timing
- widely dispersed and diffuse, subserving arousal, mood, and motivation
electrical synapses
- how fast are they?
- how do they flow?
- how are the pores and what does this mean?
extremely fast (little to no delay) with (mostly bidirectional) speed and synchrony
- allow direct passive flow of electronic current between cells via gap junctions
- pores are much larger than in voltage-gated or ligand-gated, thus permitting unselective diffusion of ions and substances like ATP and metabolites between cells
CNS synapses
electrical synapses are present in CNS, but much less common than chemical synapses
-brainstem neurons that regulate breathing are synchronized by electrical synapses
what do chemical synapses provide?
- directionality
- amplification
- potential for excitation/inhibition
- potential for plasticity/remodeling
- integration in space/time
what is necessary and sufficient for nt release?
rise in intracellular Ca++
- steep Ca++ gradient across presynaptic membrane, along with electrical gradient since positively charged
- travels through voltage-gated Ca++ channels, triggering vesicle fusion and nt release
what happens if you block voltage-gated Ca++ channels?
eliminates the postsynaptic response b/c no transmitter released
what does lowering external Ca++ concentration do?
decreases size of PSP by decreasing the number of vesicles that fuse to the membrane and release their NT
how fast is Ca clearance compared to entry?
entry of Ca++ is rapid, but clearance is slower, so Ca++ can build-up in the terminal
what is synaptic facilitation?
rapid increase in synaptic strength that occurs when 2+ AP invade presynaptic terminal w/in a few milliseconds of each other
- second EPSP is larger than the first, resulting from prolonged elevation of presynaptic Ca++ following synaptic activity
- when APs arrive in close succession, Ca++ builds up and allows more NT release in response to subsequent AP
- facilitation is not observed if 2 APs arrive far apart in time
is synaptic facilitation the same as temporal summation?
no; temporal summation is related to the number of APs and the time constant of the postsynaptic membrane
what do small molecule nt vesicles look like?
clear core, small (50 nm) vesicles made in nerve terminals (nt made in presynaptic terminal)
what do neuropeptide nt vesicles look like?
dense core, large (200 nm) vesicles synthesized in cell body and transported to nerve terminal via fast axonal, ATP-dependent transport
-vesicular release often requires high-frequency presynaptic activation
what does high-frequency stimulation lead to?
more generalized increase in Ca, causing release of both types of transmitter
relationship between active zones and postsynaptic densities
AZs - where subset of vesicles with small molecule transmitters are docked
PSDs - electron dense area with many receptors, aligned with presynaptic AZs
what is the source of the “quanta”/”quantal release” of neurotransmitters?
synaptic vesicles loaded with neurotransmitter
- Ca++ are lined up and waiting for AP to open
- vesicles can then fuse when they are stimulated
- “quantal” = simultaneous release of many discrete packets of ACh (presumably from vesicles)
how was quantal release proven?
from experiments examining ACH release
- AP in motorneuron produces depolarization of muscle cell called an endplate potential
- EPP made by quantal release, producing miniature EPPs (discharge of the contents of a single synaptic vesicle, each containing 10,000+ molecules of ACh)
what evidence is consistent with quantal release?
- fixed size of MEPPs
- quantized distribution of events occuring at NMJ
how are postsynaptic potentials produced?
PSPs are made by:
- NT released and binds to receptor channel
- conductance changes due to ion channel openings (and sometimes closings) lead to ionic current flow through channels that lead to changes in membrane potential
why do dendrites usually need EPSPs in order to transmit APs?
dendrites are thin and leaky, don’t have many Na+ channels, and thresholds for excitation are too high (decremental conduction)
-small depolarizations or hyperpolarizations in dendrites and cell somas are local, passive events
what does the glutamate binding domain consist of?
parts of both N-terminal region and loop connecting membrane-spanning segments 2 and 3
-4 of these subunits come together to form a single channel/receptor with a central pore
why is there not much NMDA activity at near resting?
glutamate ionotropic receptor
-b/c both ligand gated (Mg++) and voltage dependent
at most glutamate-mediated synapses, what is the EPSP the sum of?
2 components
- rapid component mediated by AMPA receptor channel
- slow component mediated by NMDA receptor channel
what does interposition of an inhibitory synapse in a neuronal circuit do?
can prevent overactivity in the CNS, or underlie “reciprocal inhibition” as seen in the control of antagonistic muscles
GABA-A receptor channels
mediate fast IPSP via flow of Cl- ions down electrochemical gradient
-pulse of synaptic GABA is much larger in presence of pentobarbital by increasing Cl- channel open time
GABA-B receptor channels
transduce slower GPCR signal
