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NMDA receptor-dependent Hebbian plasticity refines hippocampal spatial representations during two-dimensional navigation learning

Created on 16 Jul 2026

Authors

Reshef, R., Shahi, M., Ho, V., Ollivier, M., Arac, A., Cohen, A., Yamin, D., Tran, A., Tjondropurnomo, R., KHAKH, B. S., Aharoni, D., O'Dell, T. J., Golshani, P.

Abstract

Hippocampal place cell activity represents the location of an animal in space; yet, how hippocampal neuronal population dynamics change with spatial learning and the mechanisms underlying these activity changes, which drive allocentric navigation to a learned goal, are poorly understood. To address these questions, we performed calcium imaging with a novel wire-free waterproof miniaturized microscope to image the activity of large populations of hippocampal CA1 neurons during spatial learning of a two-dimensional navigational task, the Morris water maze. We followed the same cells during learning and were able to directly examine how each neuron in the ensemble, and the ensemble as a whole, changes its response properties. We found that neuronal spatial selectivity increased and population decoding of spatial location improved as mice learned to navigate to the goal. Viral CRISPR knock out of Grin1 (encoding the essential GluN1 NMDA receptor subunit) in dorsal hippocampal neurons, dramatically reduced long-term potentiation in CA1. This manipulation also prevented the increase in spatial selectivity and improvement of population decoding with spatial learning and resulted in learning deficits in the Morris water maze. Together, our results show that dorsal hippocampus NMDAR-dependent synaptic plasticity is essential for the learning-dependent refinement of CA1 place selectivity and improvement in population decoding of space.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 16 Jul 2026.

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