On July 27,2023, the journal Nature Communications published online the latest research results of Locomotion modifying olfactory learning through proprioception in C.elegans ( Locomotion modifying olfactory learning through proprioception in C.elegans ) by LIU Ping, a research team from the Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology.

Exercise has a significant effect on brain function, including learning and memory ability. In humans, exercise is positively correlated with children 's learning ability, and short-term strenuous exercise can instantly improve people 's learning ability. In mice, exercise enhances neuronal activity in the cerebral cortex, hippocampus, and cerebellum, and also promotes associative learning in a speed-dependent manner. In addition, exercise can also reduce the risk of neurodegenerative diseases in the elderly, and even reverse the cognitive decline of patients with neurodegenerative diseases and animal models. These studies have shown that exercise has a conservative role in promoting learning, but the neural mechanism linking exercise and learning is still unclear.

At present, it is mainly found that neurotrophic factors and muscle cytokines are involved in mediating the chronic improvement of brain function by exercise, but the neural mechanism of acute effects of exercise is still unknown. Proprioception is an excellent candidate because it senses movement speed and muscle contractions, and transmits this information instantly to the central nervous system. For example, in mammals, proprioceptive signals can reach the cerebellum and the brain through the spinocerebellar tract and the dorsal funicular-medial lemniscus pathway, respectively ; in insects, proprioceptive axons can project into the central nervous system to transmit proprioceptive signals.

Learning is a common function of animal nervous system. Model animals with simple nervous system, such as Caenorhabditis elegans, are commonly used models to study their neural circuits and synaptic mechanisms. There are only 302 neurons in C.elegans, but they exhibit multiple learning behaviors. For example, nematodes feed on bacteria. Adult nematodes naturally like the odor of pathogenic Pseudomonas aeruginosa PA14, but they can learn to avoid the odor of this pathogen after feeding PA14 for several hours. The main neurons on which PA14 olfactory learning depends have been well studied. However, unlike mammals that produce proprioception through muscle spindle and Golgi apparatus, there is a lack of specialized proprioceptive neurons in the motor neural circuit of nematodes.

In this project, the team used the simple olfactory learning of C.elegans as a model. By quantitatively analyzing the relationship between exercise speed and olfactory learning, it was found that exercise enhanced olfactory learning in a speed-dependent manner. Further, using the clear sensory motor neural circuit of C.elegans, through electrophysiology, calcium imaging, molecular genetics, optogenetics, chemical genetics and nematode behavior analysis, it was found that the motor neurons of C.elegans expressed mechanically sensitive channels and had the function of proprioceptors. Therefore, exercise can activate these neurons, and the resulting proprioceptive information is transmitted to the upstream intermediate neurons responsible for processing olfactory sensory information, regulating their experience-dependent neuronal activity and functional coupling, resulting in the regulation of olfactory learning. In this study, the function of proprioception in regulating animal learning and its fine mechanism were revealed at the level of molecule, cell, loop and animal behavior at single cell resolution.

LIU Ping, a researcher in Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, and ZHAO-Wenwang, a professor in Department of Neuroscience, School of Medicine, Kangzhou University, USA, are the corresponding authors of this paper. ZHAN Xu, a doctoral student in Department of Pathophysiology, and CHEN Chao, an orthopedic surgeon in Union Hospital, are the co-first authors of this paper. The research work is supported by the National Natural Science Foundation of China and the Independent Innovation Fund of Huazhong University of Science and Technology.