Brainstem circuits of corticospinal neurons

皮质脊髓神经元的脑干回路

• 批准号: 9977340
• 负责人: Gordon M Shepherd
• 金额: $ 69.32万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977340
• 关键词: Anatomy; Animals; Axon; Bar Codes; Behavioral; Brain Stem; Cell Nucleus; Cells; Cerebrovascular Disorders; Communication; Complement; Demyelinating Diseases; Disease; Electrophysiology (science); Foundations; Future; Goals; Health; Image; Individual; Inferior; Label; Lead; Length; Mammals; Maps; Mediating; Methods; Midbrain structure; Mission; Modeling; Molecular; Monitor; Motor; Motor Cortex; Multiplexed Analysis of Projections by Sequencing; Mus; Muscle; Neurons; Olives - dietary; Pathology; Pathway interactions; Pontine structure; Process; Property; Public Health; Pyramidal Tracts; Research; Resolution; Role; Sampling; Sensory; Signal Transduction; Slice; Source; Spinal; Spinal Cord; Spinal cord injury; Structure of nucleus cuneatus; Surveys; Synapses; System; Techniques; Textbooks; United States National Institutes of Health; Viral; base; cell type; connectome; disability; improved; in vivo; interest; locus ceruleus structure; motor behavior; motor control; motor impairment; nerve supply; nervous system disorder; neuroregulation; noradrenergic; optogenetics; postsynaptic; postsynaptic neurons; programs; reconstruction; somatosensory; subcellular targeting; systems research; tool

PROJECT SUMMARY Corticospinal axonal projections are critical for mammalian motor control. Their length and complexity makes them vulnerable to an exceptionally wide range of neurological disease processes including cerebrovascular disorders, demyelinating diseases, ALS, spinal cord injury, and more. Corticospinal research has naturally focused on cortical and spinal mechanisms. However, corticospinal axons, like those of other types of pyramidal tract neurons, can send branches to the midbrain, pons, and medulla along the way to the spinal cord. The anatomical “projectome” of corticospinal axonal branching to brainstem targets has not been systematically investigated. Even less is known about the synaptic “connectome”; i.e., the cellular circuits formed by corticospinal input to postsynaptic neurons in various brainstem nuclei. Elucidating the brainstem circuits of corticospinal axons will be important for understanding the cellular basis of mammalian motor control. For example, there very likely are as-yet unrecognized subtypes of corticospinal neurons that, through differential innervation of brainstem targets, mediate specific sensorimotor, neuromodulatory, or other functions essential for motor coordination and control. We propose a two-pronged approach to investigate the brainstem branches and circuits of corticospinal axons in the mouse. In Aim 1, we will use a high-throughput molecular barcoding technique, MAPseq, to characterize the diversity and complexity of corticospinal projections to the brainstem, with single-axon resolution and large-scale sampling. In Aim 2, we will use optogenetic, electrophysiological, imaging, and viral labeling tools to characterize the cell-type-specific synaptic connectivity in these circuits. The projections and connections of corticospinal axons’ brainstem branches will be both broadly surveyed across regions (midbrain, pons, medulla) and analyzed in a more focused manner at the level of specific types of projection neurons in key nuclei, including those associated with sensorimotor, neuromodulatory, and other systems (reticular, pontine, cuneate, locus coeruleus, and more). Results from this discovery-oriented research program will lay the groundwork for future hypothesis-oriented studies to investigate – at the mechanistically important level of specific cell types and their synaptic connectivity – how the brainstem circuits of corticospinal neurons contribute to mammalian motor function.

项目总结