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）在自愿运动的控制中起着至关重要的作用 该区域在下游电路上汇聚仍然晦涩。更好地了解M1的活动是如何 转化为适合上下文的行为，我们建议表征特定皮质投影的作用 亚型由其脊柱间神经元靶标所定义。越来越多的电生理和行为体系 有证据表明，脊髓中的间神经元子集代表功能单位，当招募时， 在强加适合任务的肌肉激活模式中发挥作用。一个例子在 相反的屈肌和伸肌的交替活性，部分由定义的脊柱回路调节。 这些电路可以过度缠绕以实现同时拮抗肌肉共激活。两个抑制性脊柱 中神经元（IN）种群，突触前GABA能（Gabapre）和相互抑制性GABA/糖苷（IA） 神经元在这种过渡中发挥作用，分别受到激活或抑制其活性。使用 最近开发的基于CVS-N2C的狂犬病追踪策略，结合了对特定基数的遗传获取 神经元人群，我们已经确定这两个类都接收直接的皮质脊髓神经元（CSN）输入。 此外，已建议该输入在适当的交替转换中发挥作用 激活屈肌肌肉对共激活。为了调查这一角色的性质，我们有 开发了一项运动行为任务，对小鼠进行了培训以替代或共同合同的前肢 肌肉响应视觉提示。现在，我们第一次可以同时监视和操纵 在运动依赖性行为过程中，CSN的定义子集的活性。