TOP一般口演
 
一般口演
リズム運動パターン制御 / 小脳
Rhythmic Motor Pattern Control / Cerebellum
座長:関 和彦(独立行政法人 国立精神・神経医療研究センター)
2022年7月2日 16:10~16:25 沖縄コンベンションセンター 会議場A2 第7会場
3O07e1-01
完全脊髄損傷者における脊髄歩行中枢の活動亢進
Aberrant activity of spinal locomotor circuitry in humans with complete spinal cord injury

*田添 歳樹(1)、村山 尊司(2)、戸坂 友也(2)、兼重 美希(1)、鈴木 迪諒(1)、菊地 尚久(3)、宇川 義一(4)、西村 幸男(1)
1. 東京都医学総合研究所 脳機能再建プロジェクト、2. 千葉リハビリテーションセンター リハビリテーション治療部、3. 千葉リハビリテーションセンター リハビリテーション科 整形外科、4. 福島県立医科大学 医学部 ヒト神経生理学講座
*Toshiki Tazoe(1), Takashi Murayama(2), Tomonari Tosaka(2), Miki Kaneshige(1), Michiaki Suzuki(1), Naohisa Kikuchi(3), Yoshikazu Ugawa(4), Yukio Nishimura(1)
1. Neural Prosthetics Project, Tokyo Metropolitan Institute of Medical Science, 2. Department of Rehabilitation Treatment, Chiba Rehabilitation Center, 3. Department of Orthopedics and Rehabilitation, Chiba Rehabilitation Center, 4. Department of Human Neurophysiology, School of Medicine, Fukushima Medical University

Keyword: Gait, Transvertebral Magnetic Stimulation, Spinal Cord

Bipedal human walking is mediated by spinal locomotor circuitry in the lumbar cord. As transvertebral magnetic stimulation (TVMS) to human lumbar cord is capable of inducing a cyclic alternative leg movement as walking, it is presumed that TVMS activates a neural module involved in the spinal locomotor circuitry to induce walking movement. Using TVMS technique, here, we aimed to discover potential adaptive changes in the spinal locomotor circuitry caused by spinal cord injury (SCI). Ten patients with chronic SCI and 7 intact controls were participated in the experiment. Four out of ten patients and the others were clinically diagnosed as incomplete and complete loss of lower extremities sensorimotor functions, respectively. The participants were in semi-prone posture on a bed with both legs suspended from the ceiling and received the bursts of TVMS via a closed-loop paradigm while legs were fully relaxed. A 6 by 3 stimulation target grid was arranged over the back that covered 6 intervertebral spaces from T11 to L5 and ~3 cm left to right from the midline. The rhythmically controlled bursts of TVMS induced the cyclic bilateral leg movements in all participants. Notably, the phase relationship between the left and right leg cycles was changed with shifting the stimulus site in all participants. However, the number of sites inducing the walking-like, left-right alternative leg movement was different among the groups. In controls and incomplete SCI, the stimulus sites inducing walking-like movement were confined to the intervertebral spaces between T11-L2. TVMS to the other sites mostly induced the hopping-like, bilateral cyclic movement in-phase. In contrast, the walking-like movements were induced at border sites in complete SCI. The complete SCI patients had more stimulus sites inducing the walking-like movements than incomplete SCI patients or controls (complete SCI=5.2±3.4; incomplete SCI=1.5±1.3; controls=2.1±1.6), whereas the stimulus sites inducing the hopping-like movements were less in complete SCI patients (complete SCI=2.2±1.2; incomplete SCI=8.3±3.4; controls=8.0±4.2). We demonstrated that the disconnection of neural pathways between the brain and the lumbar cord lead a new spinal locomotor circuitry in the humans. This new circuitry may be the primitive spinal locomotor circuitry unmasked by the SCI which disconnected the spinal locomotor circuitry with the descending commands from the brain.
2022年7月2日 16:25~16:40 沖縄コンベンションセンター 会議場A2 第7会場
3O07e1-02
運動生成回路のシナプス集団において活動時間と伝達物質の空間分布がなすモジュール構造
Module structures in spatial distribution of activity timing and transmitters of synapse population in motor generating circuits

*福益 一司(1)、能瀬 聡直(1,2)、高坂 洋史(2,3)
1. 東京大学大学院理学系研究科、2. 東京大学大学院新領域創成科学研究科、3. 電気通信大学大学院情報理工学研究科
*Kazushi Fukumasu(1), Akinao Nose(1,2), Hiroshi Kohsaka(2,3)
1. Grad Sch Sci, Univ of Tokyo, Tokyo, Japan, 2. Grad Sch Frontier Sci, Univ of Tokyo, Tokyo, Japan, 3. Grad Sch Info and Eng, Univ of Electro-Comm, Tokyo, Japan

Keyword: Drosophila larvae, motor circuits, calcium imaging, neurotransmitters

Animal behaviors are coordinated by the central nervous system (CNS), where synapses are emitting specific transmitters in proper timing. To understand such motor circuits, it is essential to reveal the activity timing and spatial position of each synapse involved in the motor processing, as well as its transmitter identity. Genetically targeting of specific neurons allows us to examine their transmitter identity and function in animal behavior. However, it is challenging to test all motor-related neurons one by one and integrate the results with such sparsely targeting experiments.
Here, we performed calcium imaging as well as immunostaining on multiple CNS samples of fly (Drosophila melanogaster) larvae, and computationally matched their morphologies. For calcium imaging, we used isolated CNSs expressing calcium indicators GCaMP in every neuron, and focused on the neuropil (a region where synapses are densely packed) in the ventral nerve cord (homologous with the spinal cord in vertebrates). During the imaging, the neuropil exhibited sequential activities corresponding to two distinct larval behaviors: forward and backward crawling. The CNSs after the imaging were stained with anti-GFP antibodies to determine the recorded position by the calcium imaging. In parallel, we applied immunostaining to other samples to reveal the distribution of glutamatergic, cholinergic, and GABAergic synapses in the neuropil. By using common landmarks in the recorded samples, all the data of synaptic activities and transmitters were spatially mapped onto a common template frame of reference.
From the data, we found that synaptic activities formed multiple module-like regions in the neuropil, where the activities were synchronized. Moreover, the data showed that the transmitter identity of synapses formed other module-like regions, in each of which synapses of a single transmitter were accumulated. By merging these module-like structures, we succeeded in revealing the spatiotemporal activity pattern of the modules of different transmitters comprehensively, and that pattern was specific to each behavioral mode. These results suggest that the synaptic activity and transmitter identity are spatially distributed not randomly but forming spatial modules in the motor circuits, which should be the substrate of the coordination of spatiotemporal motor patterns.
2022年7月2日 16:40~16:55 沖縄コンベンションセンター 会議場A2 第7会場
3O07e1-03
Multidimensional cerebellar computations for flexible kinematic control of movements
*Sungho Hong(1), Akshay Markanday(2), Junya Inoue(2), Erik De Schutter(1), Peter Thier(2)
1. Okinawa Institute of Science and Technology, 2. University of Tübingen

Keyword: manifold, saccadic eye movement, cerebellum, sensorimotor learning

Maintaining the precision of our movements critically depends on how well our movements adapt to continuously changing environments and states of the body. The cerebellum has been known to be a critical locus for this function, captured by the term sensorimotor adaptation. However, despite many studies about potentially contributing specific mechanisms in the network, the circuit-level information processing remains not well understood.

Here we report that the cerebellum performs multidimensional adaptive computations by encoding several kinematic parameters concurrently, which enables their flexible coordination for sensorimotor learning. This conclusion is based on the identification of a multidimensional, manifold-like activity in both mossy fibers (MF, network input; n=116) and Purkinje cells (PC, output; n=151), recorded from rhesus monkeys (n=2) performing a repetitive saccade task. We found the representations of individual movement parameters in the geometry and dynamics of the manifolds, which were much more selective in PCs than MFs. Error feedback-driven inputs modulated the PC manifolds in an error-type specific fashion, which predicted the parallel changes in the upcoming movements. Surprisingly, a simple MF-to-PC feed-forward network model could reproduce the PC simple spiking activity by substantially expanding small variabilities in MF input. Therefore, a compressed, low dimensional copy of sensorimotor information in the MF inputs transforms to the higher dimensional PC outputs by the cerebellar cortical circuit through variability expansion. This mechanism enables PCs to fine control individual kinematic parameters, which is necessary for the precisions in movements.

Our results demonstrate that flexible sensorimotor control and learning by the cerebellum crucially depend on its capacity for multidimensional computation.
2022年7月2日 16:55~17:10 沖縄コンベンションセンター 会議場A2 第7会場
3O07e1-04
三叉神経上核から苔状線維で伝達される口腔顔面の自己受容感覚の小脳皮質投射様態
The cerebellar cortex receives orofacial proprioceptive signals from the supratrigeminal nucleus via the mossy fiber pathway.

*堤 友美(1)、佐藤 文彦(1)、古田 貴寛(1)、加藤 隆史(2)、橘 吉寿(3)、吉田 篤(1)
1. 大阪大学大学院歯学研究科 口腔解剖学第二、2. 大阪大学大学院歯学研究科 口腔生理学、3. 神戸大学大学院医学研究科 生理学
*Yumi Tsutsumi(1), Fumihiko Sato(1), Takahiro Furuta(1), Takafumi Kato(2), Yoshihisa Tachibana(3), Atsushi Yoshida(1)
1. Dept of Oral Anatomy and Neurobiology, Osaka Univ Grad Sch Dent, Osaka, Japan, 2. Dept of Oral Physiology, Osaka Univ Grad Sch Dent, Osaka, Japan, 3. Div of Physiology and Cell Biology, Kobe Univ Grad Sch Med, Hyogo, Japan

Keyword: Mossy fiber, Muscle spindle, Trigeminal, Tract tracing

Proprioceptive sensory information from muscle spindles is essential for the regulation of motor functions. However, little is known about the motor control regions in the cerebellar cortex that receive proprioceptive signals from muscle spindles that distributed throughout the body, including the orofacial muscles. To reveal the projection patterns in the rat cerebellar cortex from the supratrigeminal nucleus (Su5), which conveys orofacial proprioception arising from jaw-closing muscle spindles (JCMSs), we performed three experiments. (1) We made injections of an anterograde tracer biotinylated dextranamine (BDA) into the Su5 identified electrophysiologicaly by responses to the masseter nerve stimulation and to sustained jaw-opening movements. Many bilateral axon terminals (rosettes) were distributed in the granular layer mainly of the hemisphere of the cerebellar cortex (including the simple lobule B, crus II, and flocculus) in a various sized, multiple patchy pattern. (2) We recorded JCMS proprioceptive signals in these cerebellar cortical areas (the simple lobule B, crus II, and flocculus) during stimulation of the masseter nerve and sustained jaw-opening movements. Then we injected a retrograde tracer Fluorogold or cholera toxin B subunit into these recording sites. These injections confirmed that the Su5 directly sends outputs to the cerebellar cortical areas. (3) We injected BDA into the external cuneate nucleus (ECu), which receives proprioceptive signals arising from forelimb and neck muscle spindles, to clarify differences between the Su5- and ECu-projection patterns in the cerebellar cortex. The labeled terminals from the ECu were distributed predominantly in the vermis of the cerebellar cortex. Almost no overlap was seen in the terminal distribution of the Su5 and ECu projections. Our findings demonstrated that the rat cerebellar cortex receives orofacial proprioceptive input that is processed differently from the proprioceptive signals from the other regions of the body.