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The effect of ketamine on the activities of and interactions between interneurons and principal cells in the dorsal hippocampus

Poster Session B - Sunday, March 8, 2026, 8:00 – 10:00 am PDT, Fairview/Kitsilano Ballroom

Audrey White¹ (), Yana M. Surtchev¹, Gabe Holguin¹, Krystina Jorgensen¹, Andrew K. Tapia¹, Zoe H. Huestis¹, Sydney H. Marean¹, Katelyn Boone¹, Carol A. Barnes^1,2, Torsten Falk¹, Stephen L. Cowen^1,2; ¹University of Arizona, ²Evelyn F. McKnight Brain Institute

Sub-anesthetic ketamine is a dissociative drug that has gained recent attention for its ability to treat psychiatric and neurodegenerative disorders such as depression and Parkinson's disease, possibly by disrupting pathological patterns of neural synchrony. Although sub-anesthetic ketamine is known to alter local-field potentials in the hippocampus, less is known about how ketamine alters interactions between individual neurons and neuron types. We examined how ketamine affects interactions between principal cells and interneurons in the dorsal hippocampus, a brain region important for memory and navigation. We predicted that ketamine would reduce between-neuron correlations. To investigate, male and female Sprague-Dawley rats (N=5) were implanted with Neuropixels probes, and recordings were acquired from the CA1, CA2, and CA3 regions of the hippocampus (AP:3.35 ML:2.8 DV:2-3.5mm) while rats were freely traversing an open field. Rats were subsequently injected with two doses of ketamine (20 mg/kg, i.p.) administered 2 hours apart. Neurons were subdivided by firing-rate and waveform width to allow analysis of putative principal cells and interneurons. Analysis of >400 single units as well as local-field potentials in the hippocampus revealed altered firing dynamics in putative interneurons and principal cells. We found that ketamine both increased and decreased firing-rate, decreased bursting activity, and altered oscillatory activity. These findings indicate that ketamine is able to disrupt neural firing patterns in the hippocampus and that ketamine could be treating psychiatric and neurodegenerative disorders by disrupting pathological patterns of neural synchrony. Supported by: NIH R01 RF1AG081767, NIH R01 NS122805-03.

Topic Area: EXECUTIVE PROCESSES: Working memory