Research Directions

While critical for survival, achieving precise body movement remains a formidable challenge. Motor command signals can become noisy, limbs may fatigue, and handled objects are often unpredictable. To achieve precision, the brain must make real-time adjustments during ongoing movements. Clinical observations and some modeling works have highlighted the cerebellum’s critical role in movement precision. However, the exact mechanisms by which the cerebellum contributes to online movement corrections remain largely unknown.

Unlike many other brain areas, the cerebellum’s basic structure, cell types, input and output have been extensively characterized. Leveraging the structural simplicity of the cerebellum, our research aims to explore its involvement in online movement corrections. Our previous findings suggest that projections from cerebellar nuclei to brainstem motor nuclei may underlie these adjustments during movement. Currently, we employ large-scale electrophysiological recording, circuit tracing, circuit manipulation, customized behavior paradigms and data analysis to study the roles of cerebellar circuits in online movement corrections.

Holding a glass of milk, brushing teeth, and tying shoelaces might all sound like simple tasks that one rarely even thinks about. However, for patients with essential tremor, all these daily routines can become very challenging. Essential tremor is reported to be the most common movement disorder, estimated to affect 1% of the general population, with its prevalence increasing with age.

Our goal is to use mouse models to elucidate the neural mechanisms of essential tremor. Our philosophy is that although essential tremor is a heterogeneous disease that can originate from different risk gene mutations and environment factors, its core symptoms are more or less the same – specifically, the action tremor. By dissecting the synaptic and circuit mechanisms that generate action tremor, we can potentially identify the final common pathway of essential tremor disease. By employing large-scale electrophysiological recording and data analysis, we can further analyze the systematic mechanisms that cause essential tremor and provide therapeutic ideas.

Within the brainstem, including the medulla, pons and midbrain, there are numerous motor brain regions that transmit motor commands to motor neurons. Currently our understanding of the structure and function of motor neural circuits in the brainstem remains very limited. Furthermore, body movement is ultimately achieved through spatiotemporally coordinated contractions of muscle groups. To fully interpret the motor execution process, we need high-throughput, non-invasive muscle activity recording techniques.

We believe that brainstem neural circuits play a pivotal role in motor control. These circuits likely receive motor decision and planning signals from upstream regions and subsequently convey concrete movement control instructions to distributed sets of interneurons and motor neurons in the spinal cord. To explore these questions, we employ cutting-edge circuit study techniques combined with AI tools to investigate roles of different brainstem motor nuclei in motor control. Our long-term goal is to elucidate how brainstem premotor neurons engage different CPGs in the spinal cord and control a wide range of body movements.