A SUBTHALAMIC GLUTAMATERGIC HUB FOR MOTOR COORDINATION

Central regulation of motor activity requires integration of complex neuronal circuits and peripheral organization. To date, diverse brain regions, neuronal subpopulations and circuits that are involved in motor activity have been deciphered, yet the complete understanding of this organization remained obscure. Loss of motor coordination is widely observed in many neurodegenerative diseases and multiple lines of evidence suggest that basal ganglia–thalamo-cortical circuits are critical regulators of motor control. The glutamatergic subthalamic nucleus (STN^vGlut2) neurons, a neuronal subset residing in this pathway, are key components of brain oscillations, however their involvement in motor activity regulation is poorly understood. We herein investigate the role of STN^vGlut2 neurons in motor coordination using chemogenetic approaches in male vGlut-cre mice by intracranially delivering rAAV-EF1a-DIO-hM3D(Gq)-mCherry, rAAV-EF1a-DIO-hM4D(Gi)-mCherry and rAAV-EF1a-DIO-mCherry. vGlut-cre mice performed open field test to observe the changes in locomotor activity upon manipulation of STN^vGlut2 neurons. Our findings suggest that activation of STN^vGlut2 neurons increased the overall speed during locomotion, yet decreased the mobility time, which might be due to high number of immobile episodes upon activation. On the contrary, STN^vGlut2 neuron silencing increased overall mobility with less immobile episodes. Considering earlier evidence and the result of this study, these findings indicate that decreased motor activity upon activation of STN^vGlut2 neurons might be due to increased pausing moments and tremor-like motor coordination loss, which are widely observed in many neurodegenerative diseases. Our data provide an understanding of STN^vGlut2 neurons not only in motor activity, but also in motor coordination loss in Parkinson-like neurodegenerative diseases.