Endocannabinoid-dependent neocortical layer-5 LTD in the absence of postsynaptic spiking.

Long-term depression (LTD) was induced in neocortical layer 5 pyramidal connections by pairing presynaptic firing with subthreshold postsynaptic depolarization (dLTD) or via a spike-timing protocol (tLTD). Like tLTD, dLTD reduced short-term depression and increased the coefficient of variation consistent with a presynaptic site of expression. Also like tLTD, dLTD was blocked by CB1 cannibinoid receptor blockade and required activation of presumably presynaptic NR2B-containing N-methyl-D-aspartate receptors. The two forms of LTD had identical magnitudes and time courses and occluded one another, and neither depended on frequency. Finally, dLTD shares with tLTD the asymmetric temporal window of induction. In conclusion, the types of LTD induced by these two protocols are indistinguishable, suggesting that the mechanism that underlies tLTD paradoxically does not require postsynaptic spiking: The subthreshold postsynaptic depolarizations of dLTD appear to fully substitute for postsynaptic spiking.