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

In mouse hippocampal area CA1, excitatory pyramidal neurons referred to as "place cells" fire at specific locations in spatial environments during navigation. Many of the excitatory inputs to place cells are themselves spatially tuned, and prior work has shown that synaptic plasticity at those inputs strongly contributes to a selective increase in excitatory synaptic conductance when an animal is inside a cell's "place field." It is less clear whether inhibitory inputs to place cells vary with spatial position. Recent studies have investigated whether place cells receive spatially tuned inhibitory conductances by recording place cell activity in vivo 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.