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The differential effects of ketamine on principal neurons and interneurons in the ventral posteromedial nucleus (VPM) of the thalamus

Poster Session C - Sunday, March 8, 2026, 5:00 – 7:00 pm PDT, Fairview/Kitsilano Ballroom

Yana M. Surtchev¹ (), Audrey White¹, 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

Evidence from our group suggests that sub-anesthetic ketamine reduces levodopa-induced dyskinesias associated with the treatment of Parkinson’s disease and that this may be through ketamine’s action on subcortical motor circuits. Ketamine’s impact on subcortical circuits is poorly understood. The ventral posteromedial nucleus (VPM) of the thalamus is a key region involved in thalamocortical communication. In motor diseases, the VPM exhibits hyperexcitability and impaired cortical signaling, contributing to disrupted sensorimotor integration. Evidence suggests that sub-anesthetic ketamine preferentially binds to NMDA receptors on parvalbumin-expressing (PV) GABAergic interneurons, resulting in reduced activation of PV neurons and a release of inhibition of excitatory neurons. However, this hypothesis has rarely been tested. To address this, we measured the activities of large populations of putative PV and principal cells in the VPM given the importance of this region for motor control. We implanted male/female Sprague-Dawley rats (N=5) with Neuropixels probes, and acquired recordings from the VPM (AP: 3.35mm ML: 2.8mm DV: 5.25-6.5mm) while rats explored an open field. Rats were injected with two doses of ketamine (20 mg/kg, i.p.), with each injection separated by 2 hours. Neurons were subdivided into putative PV neurons and principal cells by examining each neuron’s firing rate and waveform width. Analysis of >250 VPM neurons revealed varied responses to ketamine. While investigation of the selective effects of ketamine on each putative PV and principal cells is ongoing, we found that ketamine increased the overall firing rate of VPM neuron subtypes and decreased bursting activity. Support: NIH R01 RF1AG081767, R01 NS122805-03

Topic Area: PERCEPTION & ACTION: Motor control