Central synapses (general)

What are 4 features of transmission at the NMJ?

• each muscle fibre receives only one synaptic input

• each AP leads to clacium influx into presynaptic terminal and release of 100s of vesicles

• endplate potential recruits voltage gated Na channels buried in synaptic folds and reliably triggers muscle AP

• transmission is terminated by the breakdown of acetylcholine

What do neuronal subtypes differ in? (3)

• morphology

• intrinsic firing properties

• mechanisms of communication

What does the patch clamp technique enable in the CNS?

visually guided recordings from specific neuronal subtypes using blunt electrode tips readily observed under lihgt microscope

6 features of electrical synapses?

• formed by hemichannels which connect across intercellular space

• preferentially connect neurons of same subtype that are close

• good for synchronising neuronal activity

• do not provide a flexible means of synaptic communication

• bidirectional

• always excitatory

5 types of chemical transmitters?

• acetylcholine

• amines - noradrenaline, dopamine, serotonin

• amino acids - glutamate, glycine

• peptide neurotransmitters

• soluble gases

What is Dale’s principle?

all axonal branches of a neuron releasse the same neurotransmitter subtance or substances

What proportioon of synapses in CNS use glutamate and GABA?

50% glutamate

25% GABA

How many types can cortical synapses be classed into?

2

What is Gray's type 1 synapses structure and what type of synapse?

• round vesicles and assymetrical membrane specialisations

• glutamaergic

What is Gray's type 11 synapses structure and what type of synapse?

• flattened vesicles and symmetric membranes

• GABAergic

What is glutamate synthesised from and by?

from glutamine by glutaminase

What does glutamate release activate?

range of ligand-gated ion channels (iGluR) permeable to Na or Ca generatig an EPSP

What are examples of receptors expressed at glutamatergic synapses? (3)

AMPA, kainate and NMDA

What happens to glutamate?

taken up by neurons and glia rather than being broken down extracellularly

What do astrocytes do?

recycle glutamate to glutamine

When examining responses to low frequency presynaptic APs what are EPSPs mediated by?

AMPA/kainate (little contribution from NMDA)

What blocks AMPA/kainate?

NBQX

What blocks NMDA?

APV

Why are postsynaptic responses often small and variable?

many central synapses may release on average only a single vesicle for each presynaptic AP

Is a single EPSP normally not sufficient to depolarise a central postsynaptic neuron to threshold?

no

What are the two types of summation?

spatial and temporal

What may trains of APs induce?

presynaptic facilitation or depression of synaptic release

What causes facilitation of synaptic release?

residual Ca in presynaptic terminal increasing probability of vesical release following successive AP

What causes depression of synaptic release?

refractory state of release site following vesicle fusion as it reduces number of possible releasse sites until new vesicle can be primed for release

What is GABA synthesised from and by?

glutamate by glutamate decarboxylase

What are GABA receptors permeable to?

Cl and HC03

2 structural features of GABA receptors?

• pentameric

• 16 known subunit isoforms

How are vesicles loaded with GABA?

by using proton gradient

What happens to GABA remaining in synapse?

taken up by neurons and glia rather than being broken down extracellularly

Where do GABAergic synapses predominately occur?

on the soma and proximal densities

• perisomatic synapses ideally placed to veto AP generation

What are benzodiazepines?

drugs which GABA receptors are sensitive to

What do benzodiazepines do?

increase frequency of channel openings and slow down the decay of synaptic events - increase neuroinhibitory effects

What are benzodiazepines widely used as?

anxiolytics, hypnotics, anticonvulsants and myorelaxants showing important of synaptic inhibition in controlling excitability in the CNS

What are similarities between CS and NMJ? (3)

• exocytosis is driven by presynaptic Ca influx

• presynaptic boutons are filled with vesicles and transmission is quantal in nature

• fast transmission occurs via activation of ligand gated ion channels

What are differences between CS and NMJ? (4)

• CS may releasae on average only a single vesicle for each presynaptic AP - evoking weak and variable EPSPs

• CS can be inhibitory as well as excitatory

• short term facilitation/depression affects synaptic communication at excitatory and inhibitory synapses

• non cholinergic transmission (synaspes not using ACh including glutamatergic and GABAergic) is largely terminated by diffusion and reuptake