Anatomical and functional characterization of the role of projection-specific populations of corticospinal neurons in motor control

皮质脊髓神经元投射特异性群在运动控制中作用的解剖学和功能表征

• 批准号: 10224731
• 负责人: Thomas M. Jessell
• 金额: $ 41.23万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224731
• 关键词: 3-Dimensional; Anatomy; Behavior; Behavior monitoring; Behavioral; Behavioral Paradigm; Binding; Biological Assay; Calcium; Color; Contracts; Cre-LoxP; Cues; Data; Development; Dissection; Electrophysiology (science); Exhibits; Extensor; Flexor; Forelimb; Genetic; Image; Individual; Interneurons; Jaw; Label; Location; Monitor; Motor; Motor Cortex; Movement; Mus; Muscle; Muscle Contraction; Nature; Neurons; Opsin; Output; Pattern; Photons; Play; Population; Proteins; Pyramidal Cells; Rabies; Rabies virus; Role; Silicon; Spinal; Spinal Cord; Structure; Synapses; System; Testing; Time; Training; Translating; Visual; Volition; Width; base; env Gene Products; extracellular; gamma-Aminobutyric Acid; hippocampal pyramidal neuron; interest; motor control; optogenetics; postsynaptic; presynaptic; rabies viral tracing; receptor; reconstruction; recruit; response; selective expression

Abstract Motor cortex (M1) plays a crucial role in the control of voluntary movement but the neuronal mechanisms by which this region converges on downstream circuits remain obscure. To better understand how activity in M1 is translated into context-appropriate behaviors, we propose to characterize the role of specific cortical projection subtypes as defined by their spinal interneuron targets. A growing body of electrophysiological and behavioral evidence suggests that interneuron subsets in the spinal cord represent functional units that, when recruited, play a role in imposing a task-appropriate pattern of muscle activation. An example of this is seen in the alternating activity of opposing flexor and extensor muscles, which is in part regulated by defined spinal circuits. These circuits can be over-ridden to achieve simultaneous antagonist muscle coactivation. Two inhibitory spinal interneuron (IN) populations, presynaptic GABAergic (GABApre) and reciprocal inhibitory GABA/glycineric (Ia) neurons, play a role in this transition, undergoing activation or suppression of their activity, respectively. Using a recently developed CVS-N2C based rabies tracing strategy combined with genetic access to specific cardinal interneuron populations, we have identified that both classes receive direct corticospinal neuron (CSN) inputs. Moreover, this input has been suggested to play a role in the task-appropriate switching from alternating activation to co-activation of flexor-extensor muscle pairs. In order to investigate the nature of this role, we have developed a motor behavioral task in, which mice are trained to either alternate or co-contract opposing forelimb muscles in response to a visual cue. For the first time, we can now simultaneously monitor and manipulate the activity of defined subsets of CSNs during a motor-cortically dependent behavior.

摘要