Non-Hebbian long-term depression at VIP interneuron inputs

<p>Control of synaptic inhibition at the network level is essential for neuronal computation; however, the mechanism by which inhibitory I→I synapses between interneurons adjust their strength remains unclear. Here, we describe a non-Hebbian form of inhibitory long-term depression (iLTD) that operates at vasoactive intestinal peptide (VIP) interneuron inputs onto stratum oriens interneurons in the hippocampal CA1 region.<br />Repeated postsynaptic burst firing alone was sufficient to induce a persistent weakening of VIP-mediated I→I inhibitory transmission onto oriens interneurons. This plasticity was insensitive to presynaptic stimulation paired with postsynaptic burst spiking, confirming its non-Hebbian character. The observed iLTD required postsynaptic calcium influx through L- and T-type voltage-gated calcium channels but was independent of endocannabinoid signaling, indicating a postsynaptic mechanism. Physiologically relevant theta-burst stimulation of excitatory inputs to oriens interneurons induced heterosynaptic I→I iLTD and increased the excitatory/inhibitory balance in these cells, thereby enhancing their recruitment.<br />Our findings identify a cell-type-specific, activity-history–dependent rule of inhibitory I→I plasticity that weakens disinhibition in a non-Hebbian manner, revealing a novel physiological mechanism that modulates gain within hippocampal microcircuits.</p>