GABAA receptor-mediated feedforward and feedback inhibition differentially modulate hippocampal spike timing-dependent plasticity

Synaptic plasticity is believed to play an important role in hippocampal learning and memory. The precise and relative timing of pre- and postsynaptic activity has been shown to determine the sign and amplitude of hippocampal synaptic plasticity through spike timing-dependent plasticity (STDP). While most studies on STDP have mainly focused on excitatory synapses, neural networks are composed not only of excitatory synapses, but also of inhibitory synapses. Interneurons are known to make inhibitory synaptic connections with hippocampal CA1 pyramidal neurons through feedforward and feedback inhibitory networks. However, the roles of different inhibitory network structures on STDP remain unknown. Using a simplified hippocampal network model with a deterministic Ca2+ dynamics-dependent STDP model, we show that feedforward and feedback inhibitory networks differentially modulate STDP. Moreover, inhibitory synaptic weight and synaptic location influenced the STDP profile. Taken together, our results provide a computational role of inhibitory network in STDP and in memory processing of hippocampal circuits.

► Developmental maturation of interneuron network changes hippocampal STDP.
► Interneuron synaptic circuit differentially modulates hippocampal STDP.
► GABAA receptor-mediated feedback inhibition modulates tLTD only.
► GABAA receptor-mediated feedforward inhibitory network modulates both tLTP and tLTD.
► These results suggest a computational role of inhibition in hippocampal STDP.