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: 9983206
• 负责人: Thomas M. Jessell
• 金额: $ 40.97万
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9983206
• 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; 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.

抽象的 运动皮层 (M1) 在控制随意运动中起着至关重要的作用，但神经元机制 该区域在下游电路上的汇聚点仍然不​​清楚。为了更好地了解 M1 的活动情况 转化为适合情境的行为，我们建议描述特定皮质投射的作用 由脊髓中间神经元目标定义的亚型。越来越多的电生理学和行为学研究人员 有证据表明，脊髓中的中间神经元亚群代表了功能单元，当它们被招募时， 在实施适合任务的肌肉激活模式方面发挥作用。这方面的一个例子可以在 相对的屈肌和伸肌的交替活动，部分由特定的脊髓回路调节。 这些电路可以被覆盖以实现同时拮抗肌共激活。两种抑制性脊柱 中间神经元 (IN) 群体、突触前 GABA 能 (GABApre) 和相互抑制性 GABA/甘氨酸 (Ia) 神经元在这种转变中发挥作用，分别经历激活或抑制其活动。使用 最近开发的基于 CVS-N2C 的狂犬病追踪策略与特定基数的遗传获取相结合 对于中间神经元群体，我们发现这两类都接受直接皮质脊髓神经元（CSN）输入。 此外，这种输入被建议在从交替任务的任务适当切换中发挥作用。 激活到屈伸肌对的共同激活。为了探究这个角色的本质，我们有 开发了一项运动行为任务，其中训练小鼠交替或共同收缩相反的前肢 肌肉对视觉提示做出反应。我们现在第一次可以同时监控和操纵 在运动皮质依赖性行为期间定义的 CSN 子集的活动。