Cortical glutamatergic and GABAergic inputs support learning-driven hippocampal stability

Flexibility and stability of neuronal ensembles are crucial features of brain function. Little is known about how these properties of local circuits are influenced by long-range inputs. We show, in mice, that lateral entorhinal cortex glutamatergic (LEC_GLU) and γ-aminobutyric acid (GABA)-ergic (LEC_GABA) projections to CA3 recruit specific microcircuits that conjunctively provide stability to neuronal ensembles, thereby 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 inputs. This synergy allows the stabilization of spatial representations relevant to learning, as both LEC_GLU and LEC_GABA control the formation and maintenance of CA3 place cells across contexts and over time.