Endocannabinoid-mediated depolarization-induced suppression of inhibition in hilar mossy cells of the rat dentate gyrus

Hilar mossy cells represent a unique population of local circuit neurons in the hippocampus and dentate gyrus. Here we use electrophysiological techniques in acute preparations of hippocampal slices to demonstrate that depolarization of a single hilar mossy cell can produce robust inhibition of local GABAergic afferents. This depolarization-induced suppression of inhibition (DSI) can be observed as a transient reduction in frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) or as a transient reduction in amplitude of evoked IPSCs (eIPSCs). We find that DSI of eIPSCs as observed in hilar mossy cells is enhanced by activation of muscarinic acetylcholine receptors, blocked by chelation of postsynaptic calcium, and critically dependent on retrograde activation of presynaptic cannabinoid type 1 (CB1) receptors. We further report that activation of CB1 receptors on GABAergic afferents to hilar mossy cells (by either endogenous or exogenous agonists) preferentially inhibits calcium-dependent exocytosis and that endocannabinoid-dependent retrograde signaling in this system is subject to tight spatial constraints.