Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice

 Jie Zhang1 • Hao Chen2 • Li-Bin Zhang3 • Rong-Rong Li1 • Bin Wang1,4 • Qian-Hui Zhang5 • Liu-Xia Tong1,4 • Wei-Wei Zhang1 • Zhong-Xiang Yao1 • Bo Hu1,6
1 Department of Physiology, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, China 
2 Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, China 
3 948th Hospital of PLA, Wusu 833300, China 
4 College of Basic Medical Sciences, Army Medical University, Squadron 15, Battalion 5, Chongqing 400038, China 
5 Department of Foreign Language, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, China 
6 Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Army Medical University, Chongqing 400038, China
 
Abstract
The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons’ function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.
 
Keywords
Deep cerebellar nuclei; Ventromedial thalamus; Trace eyeblink conditioning; Sensorimotor learning