Whole-Brain Mapping Of Inputs To Different Thalamic Subregions Neurons Projecting To Primary Motor Cortex

The primary motor cortex(M1),as an important part of the cerebral cortex,is mainly involved in motor learning and motor control,especially any action related to delayed response,and its dysfunction is closely related to a variety of nervous system diseases(Parkinson's disease,Amyotrophic lateral sclerosis,Huntington's disease and Alzheimer's disease,etc.).The thalamus is a small structure located between the cerebral cortex and the midbrain and has extensive neural connections with both.The main function of the thalamus is to transmit motor and sensory signals to the cerebral cortex.It is also involved in regulating sleep,alertness and wakefulness-related activities,and damage to different thalamic subregions is associated with many brain-related diseases,such as schizophrenia,Parkinson's disease,epilepsy and insomnia.A large number of studies have shown that different thalamic subregions and motor cortex mediate different functions in many behavioral paradigms,which shows that thalamic subregions are closely related to M1,and their functional loops are closely related.At present,the loop and related functions between the two have been revealed by various research methods,but the mapping of inputs to different thalamic subregions neurons projecting to primary motor cortex in the whole brain are not clear.Therefore,we need to quantitatively analyze and compare the whole-brain mapping of inputs to different thalamic subregions neurons projecting to primary motor cortex,which is also a necessary prerequisite to further reveal the related complex functions.In our study,the whole-brain mapping of inputs to different thalamic subregions neurons projecting to M1 were studied by using modified rabies virus(RV)and multiple adeno-associated viruses(AAV)combined with tracing the relationship between input and output(TRIO)labeling strategy.Our study first revealed that M1 mainly receives projections from three thalamic subregions: Paracentral thalamic nucleus(PC),Parafascicular thalamic nucleus(PF)and the Central medial thalamic nucleus(CM).Through further study,we found that the whole-brain mapping of inputs to different thalamic subregions(i.e.PC-m1,PF-m1,CM-m1)neurons projecting to M1 were mostly similar.For example,they all receive inputs from different cortex and different thalamic subregions.But there are also some differences.For example,the auditory cortex,dorsal thalamic nucleus and dorsal raphe nucleus almost project to PC-m1 neurons,while paraventricular thalamic nucleus and ventral tegmental area project preferentially to PF-m1 neurons,while nucleus accumbens gives priority to CM-m1 neurons.In addition,we also found that PC-m1,PF-m1 and CM-m1 neurons in turn received specific innervation of the downstream brain region M1,forming a projection loop.In general,the whole-brain mapping of inputs to different thalamic subregions neurons projecting to primary motor cortex were quantitatively revealed for the first time by means of specific virus labeling.This provides a very important guiding significance for further revealing the complex and diversified thalamic subregions and the neural circuits and related functional studies involved in M1,and provides a solid foundation for the future study of the mechanism of diseases between thalamic subregions and M1 and the development of related drugs.