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24 Sensorimotor integration for dexterous forelimb motor control
座長:竹岡 彩(フランダースバイオテクノロジー研究所/ルーヴェン・カトリック大学)・武井 智彦(玉川大学 脳科学研究所)
2022年6月30日 16:14~16:43 沖縄コンベンションセンター 会議場B5~7 第4会場
1S04e-01
Modulation of tactile feedback for the execution of dexterous movement
*Eiman Azim(1), James M Conner(1), Andrew Bohannon(1), Masakazu Igarashi(1), James Taniguchi(1), Nicholas Baltar(1)
1. Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA

Keyword: Motor control, Sensory modulation, Tactile feedback, Cuneate

While dexterity relies on the constant transmission of sensory information, unchecked feedback can be disruptive to behavior. Yet how somatosensory feedback from the hands is regulated as it first enters the brain, and whether this modulation exerts any influence on movement, remain unclear. The cuneate nucleus in the dorsal brainstem forms the major conduit for sensory signals from the hand ascending to the sensorimotor cortex, providing a tractable location for exploring the anatomical and functional logic of feedback control. The core region of the middle cuneate receives tactile input from the distal forelimbs and is thought to specialize in processing discriminative touch signals from the hand. Cuneolemniscal neurons in this region receive afferent input and project to several subcortical targets, most predominately the ventral posterolateral nucleus (VPL) of the thalamus, which then conveys sensory information to primary somatosensory cortex. Yet, lack of circuit specific access has limited efforts to define the organization of these circuits, the relationship they might have to descending cortical pathways, and any impact putative feedback modulation might have on dexterous limb movement.

Combining molecular-genetic access in mice with anatomical studies, slice and in vivo electrophysiological recording, and high-resolution behavioral assays, we found that tactile afferents from the hand recruit neurons in the cuneate nucleus whose activity is modulated by distinct classes of local inhibitory neurons. Selective manipulation of these inhibitory circuits can suppress or enhance the transmission of tactile information, affecting dexterous behaviors that rely on movement of the hands. Investigating whether these local circuits are subject to top-down control, we identified distinct descending cortical pathways that innervate cuneate in a complementary pattern. Somatosensory cortical neurons target the core tactile region of cuneate, while a large rostral cortical population drives feed-forward inhibition of tactile transmission through an inhibitory shell. These results uncover new anatomical and functional circuit architecture for the adjustment of tactile feedback critical for the execution of dexterous forelimb behaviors. More broadly, these findings provide insight into general circuit mechanisms, analogous to those identified for other sensory pathways, that can attenuate disruptive feedback to facilitate successful behavior.
2022年6月30日 16:43~17:12 沖縄コンベンションセンター 会議場B5~7 第4会場
1S04e-02
The role of thalamocortic interactions in coordination and adaptation of voluntary movements
*Yifat Prut Prut(1)
1. The Hebrew University, Jerusalem, Israel

Keyword: Motor control, Thalamcortical, Cerebellum, NHP

The onset of voluntary movements is driven by properly timed and coordinated firing transients across a large population of motor cortical neurons. Cerebellar signals considered to play an important role in tuning this activation pattern, as is demonstrated by the motor impairments consecutive to cerebellar lesions. However, the neural mechanisms through which the cerebellum controls motor cortical activity when performing well-trained movements and during adaptation of performed action to new conditions is not fully understood. To address this question, we implanted monkeys with a chronically stimulating electrode in the superior cerebellar peduncle (SCP). Recordings were made in the sensorimotor cortex while monkeys performed a motor task. Ionophoresis was used to probe the cortical circuitry that integrates cerebellar signals. Simultaneous recording of thalamocortical activity revealed that around movement onset, thalamic cells were positively correlated with cell activity in the primary motor cortex but negatively correlated with the activity of the premotor cortex. The differences in the correlation contrasted with the average neural responses, which were similar in all three areas. We further used pharmacological perturbation to identify the cellular components of the motor cortical TC system. Application of NASPM (antagonist for Ca+2 permeable AMPA receptors) truncated the early response in a unique sub-population of SCP-responsive cells. These cells fired at higher rates, had a stronger SCP-evoked response and a narrow action potential, consistent with PV interneurons. Based on these data we classified SCP-responsive cells into Pyramidal and PV neurons. We found that PV interneurons had stronger and earlier movement-related activity compared to Pyramidal cells. In addition, PV cells had broader directional tuning but stronger correlations with movement time than Pyramidal cells. These results suggest that feedforward inhibition is employed by the CTC system and is likely the cause for the earlier recruitment of PV cells. The early inhibition may suppress competing inputs and prioritize the subsequent excitatory cerebellar drive. The consequences of this circuitry is functional cooperation and opposition between the motor thalamus and distinct motor cortical areas with specific roles in planning vs. performing movements. The CTC system can thus shape motor cortical activity despite its modest input to cortical cells.
2022年6月30日 17:12~17:41 沖縄コンベンションセンター 会議場B5~7 第4会場
1S04e-03
柔軟なフィードバック運動制御を支える運動野神経表現
Neural dynamics of motor cortex for flexible feedback motor control

*武井 智彦(1)
1. 玉川大学脳科学研究所
*Tomohiko Takei(1)
1. Brain Science Institute, Tamagawa University

Keyword: motor cortex, control policy, neural dynamics, motor preparation

A hallmark of our motor system is its ability to flexibly switch the association between sensory input and motor response. This input-output association is called the "control policy" and is assumed to be prepared according to the behavioral context prior to the initiation of action, but the neural mechanism for the preparation of control policy is largely unknown. In this study, we constructed a recurrent neural network model that reproduces the flexible motor response of monkeys to mechanical perturbations applied to the limb, and analyzed the dynamics of the neural state of the network using principal component analysis (PCA). The results showed that in response to contextual signals the neural state of the trained network progresses and waits for the forthcoming mechanical perturbation depending on the contextual signals. Then, after the mechanical perturbation was applied, the neural state deviated further to generate an appropriate motor output. Importantly, the trajectories of the neural states during the preparation and response phases were orthogonally aligned, suggesting that the preparation of the control policy can be achieved in a separate neural dimension from that for the motor response. To investigate whether a similar mechanism exists in the fronto-parietal cortical system of non-human primates, we recorded electrocorticograms (ECoGs) from a macaque monkey performing a flexible motor response task to a mechanical disturbance of the limb. The PCA showed that the cortical activity spanned orthogonal dimensions during the preparatory and response phases. These results suggest that the control policy is prepared as a state of fronto-parietal cortical activity that is separated from the dimension of motor execution.
2022年6月30日 17:41~18:10 沖縄コンベンションセンター 会議場B5~7 第4会場
1S04e-04
Cell type-specific visual information routing via the Superior Colliculus is indispensable for goal-directed forelimb reaching movements.
*Aya Takeoka(1,2,3)
1. VIB-NERF, 2. KU Leuven, Department of Neuroscience, Leuven Brain Institute, 3. imec

Keyword: forelimb control, superior colliculus, brainstem, 3D kinematics

Integration of visual information providing an object's location, shape, and size is essential for executing forelimb reaching and grasping movements. However, the primary visual cortex is not required to learn or execute the behavior. Here, we uncover that the ablation of narrow field neurons residing in the superficial layer of the superior colliculus (SC) deteriorates the refinement and execution of forelimb reaching using an intersectional approach of mouse genetics and virus-mediated circuit manipulation and high-resolution kinematic analysis. Optical-tagging of narrow field neurons reveals activity tuning to a specific kinematic phase during reaching. They preferentially form synaptic connections to glutamatergic neurons in the intermediate SC (iSC) projecting to the pontine reticular nuclei (PRN). Selective ablation of the iSC-PRN projection neurons impairs the consistency of reaching kinematics, but not digit movements for grasping, indicating that the superior colliculi encode visual information necessary for the end-point refinement. Moreover, the projection neurons receive input from diverse motor and sensory processing-related structures. Together, our study reveals cell type-specific visual information routing via the superior colliculus that regulates forelimb reaching behavior.