Inhibitory Gating of Input Comparison in the CA1 Microcircuit

Spatial and temporal features of synaptic inputs engage integration mechanisms on multiple scales, including presynaptic release sites, postsynaptic dendrites, and networks of inhibitory interneurons. Here we investigate how these mechanisms cooperate to filter synaptic input in hippocampal area CA1. Dendritic recordings from CA1 pyramidal neurons reveal that proximal inputs from CA3 as well as distal inputs from entorhinal cortex layer III (ECIII) sum sublinearly or linearly at low firing rates due to feedforward inhibition, but sum supralinearly at high firing rates due to synaptic facilitation, producing a high-pass filter. However, during ECIII and CA3 input comparison, supralinear dendritic integration is dynamically balanced by feedforward and feedback inhibition, resulting in suppression of dendritic complex spiking. We find that a particular subpopulation of CA1 interneurons expressing neuropeptide Y (NPY) contributes prominently to this dynamic filter by integrating both ECIII and CA3 input pathways and potently inhibiting CA1 pyramidal neuron dendrites. •Excitatory and inhibitory input summation in CA1 is nonlinear and frequency-dependent•CA1 pyramidal cells report coincidence of CA3 and ECIII inputs with complex spikes•NPY+ but not PV+ or SST+ interneurons in CA1 also integrate both input pathways•NPY+ interneurons in CA1 potently inhibit dendritic excitability in pyramidal cells CA3 and ECIII inputs to CA1 target distinct dendritic domains of pyramidal cells and recruit specific classes of interneurons. Milstein et al. quantify contributions by short-term plasticity, dendritic amplification, and compartmentalized inhibition to synaptic filtering dynamics during dual pathway integration.