Spike-timing-dependent plasticity of neocortical excitatory synapses on inhibitory interneurons depends on target cell type.

Repetitive correlated spiking can induce long-term potentiation (LTP) and long-term depression (LTD) of many excitatory synapses on glutamatergic neurons, in a manner that depends on the timing of presynaptic and postsynaptic spiking. However, it is mostly unknown whether and how such spike-timing-dependent plasticity (STDP) operates at neocortical excitatory synapses on inhibitory interneurons, which have diverse physiological and morphological characteristics. In this study, we found that these synapses exhibit target-cell-dependent STDP. In layer 2/3 of the somatosensory cortex, the pyramidal cell (PC) forms divergent synapses on fast spiking (FS) and low-threshold spiking (LTS) interneurons that exhibit short-term synaptic depression and facilitation in response to high-frequency stimulation, respectively. At PC-LTS synapses, repetitive correlated spiking induced LTP or LTD, depending on the timing of presynaptic and postsynaptic spiking. However, regardless of the timing and frequency of spiking, correlated activity induced only LTD at PC-FS synapses. This target-cell-specific STDP was not caused by the difference in the short-term plasticity between these two types of synapses. Activation of postsynaptic NMDA subtype of glutamate receptors (NMDARs) was required for LTP induction at PC-LTS synapses, whereas activation of metabotropic glutamate receptors was required for LTD induction at both PC-LTS and PC-FS synapses. Additional analysis of synaptic currents suggests that LTP and LTD of PC-LTS synapses, but not LTD of PC-FS synapses, involves presynaptic modifications. Such dependence of both the induction and expression of STDP on the type of postsynaptic interneurons may contribute to differential processing and storage of information in cortical local circuits.