Long-term Depression - Spike Timing-dependent Plasticity

Spike Timing-dependent Plasticity

Spike timing-dependent plasticity (STDP) refers to the timing of presynaptic and postynaptic action potentials. STDP is a form of neuroplasticity in which a millisecond-scale change in the timing of presynaptic and postsynaptic spikes will cause differences in postsynaptic Ca2+ signals, inducing either LTP or LTD. LTD occurs when postsynaptic spikes precede presynaptic spikes by up to 20-50 ms. Whole-cell patch clamp experiments "in vivo" indicate that post-leading-pre spike delays elicit synaptic depression. LTP is induced when neurotransmitter release occurs 5-15 ms before a back-propagating action potential, whereas LTD is induced when the stimulus occurs 5-15 ms after the back-propagating action potential. There is a plasticity window: if the presynaptic and postsynaptic spikes are too far apart (i.e., more than 15 ms apart), there is little chance of plasticity. The possible window for LTD is wider than that for LTP – although it is important to note that this threshold depends on synaptic history.

When postsynaptic action potential firing occurs prior to presynaptic afferent firing, both presynaptic endocannabinoid (CB1) receptors and NMDA receptors are stimulated at the same time. Postsynaptic spiking alleviates the Mg2+ block on NMDA receptors. The postsynaptic depolarization will subside by the time an EPSP occurs, enabling Mg2+ to return to its inhibitory binding site. Thus, the influx of Ca2+ in the postsynaptic cell is reduced. CB1 receptors detect postsynaptic activity levels via retrograde endocannabinoid release.

STDP selectively enhances and consolidates specific synaptic modifications (signals), while depressing global ones (noise). This results in a sharpened signal-to-noise ratio in human cortical networks that facilitates the detection of relevant signals during information processing in humans.