Hippocampal Place Cells with NMDARs Do Not Require Excitation and Inhibition to Be Reciprocally Tuned

and using computational models to help interpret experimental perturbations. One prior study used inhibitory optogenetics to suppress inhibitory neuron firing rates and observed a uniform depolarization of place cells across spatial locations, supporting a model with spatially uniform synaptic inhibition. In apparent conflict, other studies used excitatory optogenetics to depolarize place cells and observed a selective increase in excitability within place fields, supporting a model with a spatially localized decrease in inhibition. However, the latter studies overlooked the contribution of voltage-gated NMDA-type glutamate receptors (NMDARs) to synaptic integration, which are expected to contribute to the balance of excitatory and inhibitory synaptic currents. Here we show that when NMDARs are included at excitatory synapses in simple CA1 place cell models, all experimentally-observed properties of place cells can be recapitulated regardless of whether inhibition increases, decreases, or remains constant inside a place field. Significance Statement: The hippocampus is a brain region required for the formation of new spatial and episodic memories (what happened where and when). Investigating the cellular and circuit mechanisms of memory recall could identify targets for therapies to combat memory decline associated with aging or neurodegeneration. Here we compare the results of computational models of the hippocampus to experimental recordings from mice to better understand the contribution of inhibitory neurons to the expression of spatial memories. We find that a special type of glutamate receptor, the NMDA receptor, helps to maintain the spatial selectivity of excitatory neurons in the hippocampus by counter-balancing fluctuations in the magnitude of inhibitory synaptic currents.