Cortico-Hippocampal Circuit Interactions in Shaping Place Cell and Memory Functions

Abstract

Stability and flexibility of neuronal ensembles are crucial brain functions, notably supporting learning and memory. However, little is known about how these features of local circuits are influenced by long-range inputs allowing communication across brain regions. Here, we show that lateral entorhinal cortex glutamatergic (LEC_GLU) and GABAergic (LEC_GABA) projections to CA3 recruit specific microcircuits that conjunctively provide stability to neuronal ensembles supporting learning. LEC_GLU drives excitation in CA3 but also substantial feedforward inhibition that prevents somatic and dendritic spikes. Conversely, LEC_GABA suppresses this local inhibition to disinhibit CA3 activity with compartment- and pathway-specificity by selectively boosting somatic output to integrated LEC_GLU and CA3 recurrent network inputs. This synergy allows the stabilization of spatial representations relevant to learning, as both LEC_GLU and LEC_GABA control the remapping of CA3 place cells across contexts and over time. Overall, our findings provide circuit mechanisms whereby long-range glutamatergic and GABAergic cortico-hippocampal inputs cooperatively shape experience-dependent spatial coding in CA3.