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Ketamine reduces variability in firing frequency and modulates firing rate in the motor thalamus

Poster Session F - Tuesday, April 1, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Yana M. Surtchev1 (yana.mms@gmail.com), Gabe Holguin, Audrey White, Krystina Jorgensen, Andrew K. Tapia, Zoe H. Huestis, Sydney H. Marean, Katelyn Boone, Carol A. Barnes, Torsten Falk, Stephen L. Cowen; 1University of Arizona

Ketamine is a powerful general anesthetic that has received renewed interest as a treatment for depression, post-traumatic stress disorder (PTSD), and Parkinson’s dyskinesia. Little is known about how ketamine exerts its powerful effects on mood, disease, and perception. Given that the thalamus is a hub connecting nearly all neural systems involved in sensation, perception, and pro-locomotor effect in rodents, we hypothesized that individual neurons in the thalamus would show strong changes in firing rates for at least 1 hour following ketamine injection. Naïve male and female Sprague-Dawley rats (N=4) were implanted with Neuropixels probes (AP: -3.35 ML: +2.8 DV:-5.05-6.7), and recordings were acquired from the thalamic ventral posteromedial nucleus (VPM) while rats were freely traversing an open field. Rats were subsequently injected with two doses of ketamine (20 mg/kg) in two-hour intervals. Preliminary analysis of >250 neurons in 1 rat revealed strong but varying responses over the 25-minute post injection period, such that ketamine reduced ‘burst-like’ responses as indicated by a reduced short-latency peak in an autocorrelogram. Additionally, the firing rate both increased and decreased across cells during the 5-25 minute post-injection period, suggesting that ketamine has differential effects on various cell types across the VPM axis. This reduction in firing variability and fluctuations in firing rate may be due to ketamine’s action as a glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonist that may down-regulate neurons supporting the therapeutic effects of ketamine in depression, PTSD, and PD.

Topic Area: PERCEPTION & ACTION: Motor control

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March 29–April 1  |  2025

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