Atypical hippocampal excitatory neurons express and govern object memory

Classically, pyramidal cells of the hippocampus are viewed as flexibly representing spatial and non-spatial information. Recent work has illustrated distinct types of hippocampal excitatory neurons, suggesting that hippocampal representations and functions may be constrained and interpreted by these underlying cell-type identities. In mice, here we reveal a non-pyramidal excitatory neuron type — the “ovoid” neuron — that is spatially adjacent to subiculum pyramidal cells but differs in gene expression, electrophysiology, morphology, and connectivity. Functionally, novel object encounters drive sustained ovoid neuron activity, whereas familiar objects fail to drive activity even months after single-trial learning. Silencing ovoid neurons prevents non-spatial object learning but leaves spatial learning intact, and activating ovoid neurons toggles novel-object seeking to familiar-object seeking. Such function is doubly dissociable from pyramidal neurons, wherein manipulation of pyramidal cells affects spatial assays but not non-spatial learning. Ovoid neurons of the subiculum thus illustrate selective cell-type-specific control of non-spatial memory and behavioral preference.