Long-range inhibitory projections gate cortico-hippocampal information flow.

Top Left, Entorhinal cortex (EC) excites CA1 pyramidal neurons (PN) directly (PP) and indirectly (ECe→DGe→CA3e→CA1). EC also sends direct long-range inhibitory projections (LRIP) to CA1. Top Right, LRIPs (green) and dye-filled CA1 PN and inhibitory interneuron (IN). Bottom, Disinhibitory effect of LRIPs. IN (top) and PN (bottom) recordings with LRIPs active (blue) or silenced (red). EC stimulation evokes mixed excitation/inhibition (EPSP/IPSP) in IN. Schaffer collateral, SC-evoked dendritic depolarization is enhanced when preceded by EC stimulation (20 ms delay) because LRIPs inhibit INs (disinhibition). Ten or more EC-SC paired stimuli (1 pair/s) trigger PN dendritic spikes (d-spikes). 90 s of EC-SC pairing induces input timing-dependent plasticity (ITDP) leading to long-term potentiation in SC-evoked PN excitation. LRIP silencing (red traces) decreases dendritic depolarization and spike firing, and blocks ITDP.