Inhibitory gating in the Dentate Gyrus

Electrophysiological recordings have demonstrated a tight inhibitory control of hilar interneurons over Dentate Gyrus granule cells (DGgc). This excitation/inhibition balance is crucial for information transmission and likely relies on inhibitory synaptic plasticity. Our experiments show that LTP induction in perforant pathway, not only potentiate glutamatergic synapses, but unexpectedly decrease feed-forward inhibition in the DG, facilitating activity propagation in the circuit. To investigate this phenomenon we propose a model based on the Izhikevich’s neuronal equations. The model contains entorhinal cortex (EC) neurons, DGgc, mossy cells and two populations of hilar interneurons, basket and Hil cells. The results obtained from the numerical integration of the model equations, before and after LTP induction, support the counterintuitive experimental observation of a synaptic depression in the feed-forward inhibitory connection induced by LTP. The key role of basket cells is confirmed in pharmacogenetic experiments conducted in parvalbumin-cre mice in which the activity of this cell type can be selectively enhanced or depressed. Overall, our findings suggest that LTP of the EC input increases the excitation/inhibition balance and facilitates activity propagation to the next station in the circuit by recruiting an interneuron- interneuron network that inhibits the tight control of basket cells over DGgc firing.