[Research Article] Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition

LRIPs from LEC produced strong inhibitory postsynaptic potentials in a large fraction of CA1 interneurons located in the region of the EC inputs. Although pharmacogenetic silencing of LRIPs in hippocampus did not prevent CFC or NOR memory, it caused mice to show an inappropriate fear response to a neutral context and a diminished ability to distinguish a novel object from a familiar object. Calcium imaging revealed that the LRIP axons and presynaptic terminals responded to various sensory stimuli. Moreover, pairing such signals with appetitive or aversive stimuli increased LRIP activity, consistent with a role of the LRIPs in memory specificity. Intracellular recordings demonstrated that the LRIPs powerfully suppressed the activity of a subclass of cholecystokinin-expressing interneurons (CCK INs). These interneurons were normally strongly excited by the CA3 inputs, which results in pronounced feedforward inhibition (FFI) of CA1 pyramidal neuron dendrites.