TRESK POTASSIUM CHANNEL DIFFERENTIALLY REGULATES CEREBELLAR MOTOR LEARNING AND COORDINATION IN MALE AND FEMALE MICE

Ion channel function is critical for establishing neuronal excitability and regulating synaptic transmission throughout the nervous system, thereby influencing motor control and behavioral output. K2P potassium channels, modulate the intrinsic excitability of neurons by controlling background potassium conductance. TRESK (K2P18.1), a two-pore domain potassium channel, is expressed across multiple brain regions including the cerebellum, yet its specific role in cerebellar function and motor behavior remains unclear. This study investigates how TRESK influences cerebellar neuronal properties and motor performance using a TRESK knockout (KO) mouse model. RNAscope in situ hybridization shows significant TRESK expression in both excitatory and inhibitory cerebellar neurons. Analysis of available databases of single-nucleus transcriptomic data revealed that TRESK is preferentially enriched in cerebellar inhibitory interneurons, particularly Golgi cells and Purkinje layer interneurons, suggesting a specialized role in modulating cerebellar inhibitory tone. Electrophysiological analysis is currently underway to characterize how TRESK deletion affects cerebellar neuron firing properties and synaptic function. Behavioral phenotyping of TRESK knockout mice revealed sex-dependent motor deficits: in the accelerated rotarod test, male KO mice demonstrated altered motor learning trajectories with greater trial-to-trial variability compared to wild-type or female KO mice. Female KO mice displayed significantly poorer balance and coordination in the ledge test and a higher kyphosis score. These findings demonstrate that TRESK modulates cerebellar motor circuits in a sex-dependent manner and suggest that altered TRESK function may contribute to motor coordination deficits. This work provides insights into the role of leak potassium channels in cerebellar physiology and motor behavior.