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.