Why does the order of two spikes, a few milliseconds apart, decide whether a synapse strengthens or weakens? · Grey Matter

In spike-timing-dependent plasticity, a presynaptic spike arriving a few milliseconds before the postsynaptic spike strengthens the synapse, and one arriving just after weakens it, within a window of about 20 ms on each side in Bi and Poo's hippocampal cultures.

Why does the order of two spikes, a few milliseconds apart, decide whether a synapse strengthens or weakens?

In spike-timing-dependent plasticity, a presynaptic spike arriving a few milliseconds before the postsynaptic spike strengthens the synapse, and one arriving just after weakens it, within a window of about 20 ms on each side in Bi and Poo's hippocampal cultures. The NMDA receptor explains much of it: if glutamate binds first and the postsynaptic spike then back-propagates into the dendrite and expels the magnesium, a large burst of calcium enters, which favours potentiation. If the postsynaptic spike comes first, the depolarisation has passed by the time glutamate arrives, calcium entry is small, and depression follows. The rule rewards inputs that could have caused the spike and punishes those that came too late, a causal refinement of Hebb's idea.