This diagram shows several key features a typical Hebbian synapse. The transmitter glutamate is released from vesicles (orange) when a presynaptic spike arrives. This stimulates both AMPA-type receptors (green) and NMDA-type receptors (blue). The NMDARs generate very little current, because when they open they are immediately blocked by extracellular magnesium ions. The AMPARs generate an inward sodium current which depolarizes the spine head, and less strongly and with a slight delay, the cell body and the axon initial segment. If a lot of other synapses fire at roughly the same time, these small somatic depolarizations can add up and trigger a spike, which travels down the axon to the neuron's output synapses made on other neurons. But this spike also travels back along the dendrites, and reaches the synapse shown here (and the others that help trigger the spike). This pops out the Mg from the open NMDARs, which allows calcium to enter (shown as a red cloud; a few calcium ions are already around at rest). This calcium signal can then trigger, via CaMkinase, strengthening of the synapse by addition of more AMPARs (either from perisynaptic membrane and/or an intracellular source).
IMPORTANT POINTS
(1) the briefly open AMPARs do not permit Ca entry (Q/R switch)
(2) the unplugged open NMDARs do ; this Ca signal triggers LTP (or perhaps LTD)
(3) the occurrence of a back-propagating spike reflects the cooperative action of the firing of many individually weak synapses, each resembling that shown here, but varying in "strength" (= numbers of AMPARs).
(4) some synapses lack AMPARs - they are "silent". However, they can be unsilenced in exactly the same way as shown here.
(5) If a backpropagating spike should arrive prematurely, before a presynaptic spike releases glutamate, or not at all, there is a much smaller calcium signal in the spine head (and therefore no LTP) but the early bAP can cause e.g. endocannabinoid release, which combined with subsequent stimulation of another type of presynaptic NMDARs (not shown), can cause, in the future, less transmitter release, weakening the synapse ("LTD").
(6) the calcium signal (and other second messengers underlying ltp/ltd) does not significantly spread to neighboring synapses, despite their extremely close packing (~ 1 um apart or less) and their rapid diffusion (~ 1 um^2/msec). Of course the devil is in that "significantly". My own research focuses on this rather neglected but crucial issue - more anon.
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