Synaptic Transmission Flashcards by Nicole King

Electrical synapses (gap junctions) allow

very fast, bidirectional communication between cells
→ useful to generate rhythms (e.g. for breathing) and
oscillations (e.g. interneuron networks).
exchange of small molecules like ATP, cAMP, sugars
→ relevant for large networks of glial cells that control
neuronal metabolism

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Function of Electrical Synapes - Gap Junctions

Allow for direct electrical communication between cells
Allow for chemical communication between cells, through the transmission of small second messengers, such as inositol triphosphate (IP3) and calcium (Ca2+)
Metabolic coupling

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Chemical synapses

Translating an
electrical signal into a
chemical signal and
right back into an
electrical signal

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The most common type is contact between

an axon terminal and a dendritic, somatic, or axonal domain

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The Neuromuscular junction (NMJ)

Large postsynaptic cell
* One axon (but about 100 synapses !)
per muscle cell
* Highly reliable
– Most pre-synaptic action potentials lead
to a post-synaptic action potential
* Chemical signaling is simple
– Only one type of ion channel

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END PLATE POTENTIAL (EPP)

Stimulation of the motor fiber
generates a synaptic potential in the post-synaptic muscle cell.

~40-50mV amplitude

Action potentials synchronize the release of many transmitter quanta

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Miniature End Plate Potentials (MEPPs)

very small (miniature) potentials (~1 mV) occur even in the absence of stimulation

Eliminated in instances with redued extracellular Ca2+

EPPs are multiples of MEPPs

(Spontaneous) Neurotransmitter release occurs in quantal packets

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Quantal release theory

Key variables that characterize quantal (vesicular) release:

the number of release sites (N)
the probability of a quantal release (p)
the size of the quantal response (q)

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Quantal analysis

the distribution of amplitudes of
the postsynaptic response can be
fitted to a binominal distribution
→ From this, the best-fitting values of N, p, and q can be extracted

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Morphological correlates of Katz’s variables

the number of release sites (N)

number of active zones/synapses

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Morphological correlates of Katz’s variables

the probability of a quantal release (p)

number of docked vesicles

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Morphological correlates of Katz’s variables

the size of the quantal response (q)

single vesicle and/or the response to a single vesicle (receptor sensitivity)

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____is required for transmitter release (influences the probability of release)

Calcium

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Presynaptic action potentials open

voltage-gated Ca2+ channels.

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Ca2+ allows vesicles

to fuse
with the membrane

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2-fold increase in Ca2+ can

increase
transmitter release 16-fold

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Infusion of a
Ca2+ chelator such as BAPTA

reduces Ca2+
release

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Action-potential triggers

Ca2+ influx into presynaptic terminal via voltage-gated Ca2+ channels (N- and/or P/Q type)

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In the active zone, Ca2+ currents are

10x larger
than elsewhere.

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In the active zone, Ca2+ can rise

1000-fold (to ~100 µM)

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SNAREs (SNAp REceptors)

group of proteins that promote
fusion of the vesicle and presynaptic membrane.

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Steps involved in vesicle release and recycling

Trafficking
Tethering
Docking and Priming
Fusion
Endocytosis

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Trafficking

target vesicles to
the active zone

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Tethering

restrain vesicles in reserve pool

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Docking and priming

vesicles to active zone

Fusion AKA

exocytosis

Endocytosis

retrieve fused membrane (recycling)

4-AP blocks K+ channels and prolongs the action potential and thus

tincreases the amount of Ca2+ that can enter → leads to more quanta released per AP → Correlates perfectly with number of fused vesicles counted in EM

The fusion of a transport vesicle with its target involves 2 types of events:

The transport vesicle must recognize the correct target membrane. * Second, the vesicle and target membranes must fuse, so that the content of the vesicle can be delivered to the target organelle (within the cell) or into the synaptic cleft.

The SNARE hypothesis describes

vesicle fusion via the interaction between specific pairs of transmembrane proteins, called SNARES (SNAP [Soluble NSF Attachment Protein] Receptor)

Two (main) types of SNAREs

vesicle or v-SNAREs (or R-SNAREs), target or t-SNAREs (or Q-SNARES)

vesicle or v-SNAREs (or R-SNAREs)

incorporated into the membranes of transport vesicles during budding

Example of a v-SNARE

* Synaptobrevin sits in the vesicle membrane

target or t-SNAREs (or Q-SNARES)

located in the target membranes

Examples of t-SNAREs

* Syntaxin and SNAP-25 are anchored in the presynaptic membrane (T-SNAREs)

Calcium sensor (not a SNARE) involved in Exocytosis

Synaptotagmin | or VAMP (vesicle associated membrane protein)

Functions of Synaptotagmin-1

Calcium Sensor – Releases clamp on release, or facilitates release. Involved in docking and vesicle fusion via interaction with βneurexin or SNAP-25 Also aids in recycling – binds clathrin

Neurexins

interaction with synaptotagmin leads to fusion

The SNARE complex binds

directly to N-type Ca++ channels

Two neurotoxins that effect SNAREs

Botulinum neurotoxin and Tetanus neurotoxin

Botulinum neurotoxin

cleaves SNARE proteins

Tetanus neurotoxin

cleaves Synaptobrevin

The “classic” synaptic vesicle cycle Duration

~ 1 min

Two key proteins for Endocytosis

* Clathrin * Dynamin

clathrin

forms coated pits by curving the membrane

dynamin

pinches of coated vesicle

Synaptotagmin I is involved in

both sides of the vesicle cycle. Synaptotagmin serves as anchor for AP2. Clathrin attaches to AP2 or synaptotagmin itself

Four different modes of endocytosis

1. “kiss and run” 1. Clathrin-mediated 1. Bulk endocytosis 1. “Ultrafast”

Duration of "kiss and run" endocytosis

1 sec

Duration of Clathrin-mediated endocytosis

tens of seconds

Duration of Bulk endocytosis

tens of seconds, requires strong stimulation

Duration of “Ultrafast” endocytosis

50-100 ms

Function of Synapsin

keeps vesicles tethered in the reserve pool * cross-links vesicles to cytoskeletal filaments (f-actin)

Synapsin is regulated by

Ca2+/Calmodulin-dependent kinase (CaMKII) and PKA

Phosphorylation of Synapsin

frees vesicles to move.

Rab proteins | (members of the Ras superfamily of G-proteins)

Small GTP-binding protein mark transport vesicles * interact with v-SNAREs to initiate fusion

Rab GTPases regulate

many steps of membrane traffic, including vesicle formation, vesicle movement along actin and tubulin networks, and membrane fusion

more than __ different Rab proteins are involved in vesicle transport

Neurexins (NRXN) are

presynaptic cell adhesion proteins. The intracellular portion of NRXN interacts with SNAREs, while their extracellular domain interacts with proteins in the synaptic cleft, most notably neuroligin.

Neuroligin 1 (NLGN1) is

enriched at excitatory synapses

NLGN2 is

enriched at inhibitory, dopaminergic and cholinergic synapses

NLGN3 is

found at both excitatory and inhibitory synapses,

Neurexin and neuroligin

"shake hands," resulting in the production of a synapse Neurexin (presynaptic); Neuroligin (postsynaptic)

An EPSP has a reversal potential more

positive than the AP threshold

an IPSP has a reversal potential more

negative than threshold

# Post-synaptic responses Excitatory Input

- often glutamate or ACh - permeable to both Na+ and K+

# Post-synaptic responses Inhibitory Input

- usually GABA - permeable to Cl-

Direction of post-synaptic potential determined by:

* The ionic identity * The equilibrium (reversal) potential of that ion

Two types of post-synaptic receptors

* Ionotropic * Metabotropic

Ionotropic Receptors

ligand-gated channels → receptor IS channel; immediate conductance change

Metabotropic receptors

G-protein-coupled receptors → receptor modulates channel, or other intracellular effects; delayed, longer lasting response

Binding of ligand (e.g. ACh) to receptor has

similar effects as changes in membrane potential on voltage-gated channels.

The reversal potential can be used to

determine which ions flow during synaptic currents

Because under physiological conditions the driving force for Na+ is much higher, activation of the receptor typically results in

an inward current and an EPSP

Synaptic Transmission Flashcards

(74 cards)