Adaptive Mossy Cell Circuit Plasticity after Status Epilepticus

Hilar mossy cells regulate network function in the hippocampus through both direct excitation and di-synaptic inhibition of dentate granule cells (DGCs). Substantial mossy cell loss accompanies hippocampal circuit changes in epilepsy. We examined the contribution of surviving mossy cells to network activity in the reorganized dentate gyrus after pilocarpine-induced status epilepticus (SE). To examine functional circuit changes, we optogenetically stimulated mossy cells in acute hippocampal slices from male mice. In control mice, activation of mossy cells produced monosynaptic excitatory and di-synaptic GABAergic currents in DGCs. In pilocarpine-treated mice, mossy cell density and excitation of DGCs were reduced in parallel, with only a minimal reduction in feedforward inhibition, enhancing the inhibition/excitation ratio. Surprisingly, mossy cell-driven excitation of parvalbumin-positive (PV1) basket cells, primary mediators of feed-forward inhibition, was maintained. Our results suggest that mossy cell outputs reorganize following seizures, increasing their net inhibitory effect in the hippocampus.