Synaptic modifications in cultured hippocampal neurons: Dependence on spike timing, synaptic strength, and postsynaptic cell type

In cultures of dissociated rat hippocampal neurons, persistent potentiation and depression of glutamatergic synapses were induced by correlated spikin g of presynaptic and postsynaptic neurons. The relative timing between the presynaptic and postsynaptic spiking determined the direction and the exten t of synaptic changes. Repetitive postsynaptic spiking within a time window of 20 msec after presynaptic activation resulted in long-term potentiation (LTP), whereas postsynaptic spiking within a window of 20 msec before the repetitive presynaptic activation led to long-term depression (LTD). Signif icant LTP occurred only at synapses with relatively low initial strength, w hereas the extent of LTD did not show obvious dependence on the initial syn aptic strength. Both LTP and LTD depended on the activation of NMDA recepto rs and were absent in cases in which the postsynaptic neurons were GABAergi c in nature. Blockade of L-type calcium channels with nimodipine abolished the induction of LTD and reduced the extent of LTP. These results underscor e the importance of precise spike timing, synaptic strength, and postsynapt ic cell type in the activity-induced modification of central synapses and s uggest that Hebb's rule may need to incorporate a quantitative consideratio n of spike timing that reflects the narrow and asymmetric window for the in duction of synaptic modification.