the same cellular mechanisms that supported excitatory synaptic transmission at the neuromuscular junction are active in the CNS
1 synaptic vesicle
Þ post synaptic potential (psp); Ý with Ý # of synaptic vesicles
glutamate (not ACh) is the neurotransmitter at most excitatory synapses
synaptic junctions at excitatory synapses in the CNS often utilize glutamate as a transmitter
the details of the junction structure vary at different classes of synapse
excitatory synapse (glu): post-synaptic electron-dense material is thicker than the presynaptic membrane
inhibitory synapse (gaba): symmetric pre and post synaptic electron-dense specializations
the effect of one axon on a cell is integrated with the effects of many others (very rarely a 1:1 correspondence between input and output)
usually 1 synapse interacts with many others to influence activity of postsynaptic cell
for example: purkinjie cell in cerebellum forms 40,000-100,000 synapses with parallel fiber axons
1 synapse has small effect, but many synapses can change firing rate of purkinjie cell
position on dendritic arbor is important
synapse in proximal dendrites has greater effect than synapse on distal dendrite
importance of dendritic spine
majority of excitatory synapses in CNS are located on dendritic spines
hypothesis: spines represent site of synaptic plasticity
if diameter of spine changes, amplitude and duration of synaptic potential would also change
Three Types of Glu Receptors
– each supports a different aspect of synaptic transmission
(1) "standard" excitatory synaptic transmission
ligand gated channel analogous to nicotinic acetylcholine receptor
activated by glu and its analogs (kainic acid, quisqualate, AMPA)
probably made up of several subunits
(2) NMDA receptors and long term synaptic potentiation
May change the way it works from second to second; selective agonist
e.g., mammalian hippocampus: pyramidal cells of CA3 synapse pyramidal cells of CA1
low rate stimulus
Þ uniform post-synaptic response using ligand gated channels
brief high frequency stimulus, then subsequent stimuli
Þ much larger post-synaptic response
this can last for months (model for memory); uses NMDA receptors
at normal potentials, Mg occupies the channel
depolarization
Þ Mg leaves Þ glu binds and opens Þ Ca++ current Þ long-term response
antagonist
Þ normal synaptic transmission but no long term potentiation induced
(3) The "metabotropic" glutamate receptor
coupled to G-protein
stimulates inositol phosphate/Ca++ signal transduction
Excitotoxicity
normally, action of Glu is terminated by diffusion from synaptic cleft, followed by removal from extracellular space by uptake into astrocytic processes
hypoxic neurons fire repetitively while hypoxic astrocytes are unable to clear all Glu
Glu occupying NMDA could cause large and persistent influx of Ca++ which activates proteases and causes cell death (self-digestion)
research is aimed at blocking this NMDA channel to prevent neuronal destruction in stroke