Biology subjects

Takei, T.

Publications and source records attributed to Takei, T..

11 recordsLinked to original sources

bioRxiv2025

Autogenic spinal excitatory circuit ensures skilled hand movements in primates

Skillful hand movements are a hallmark of primates, including humans, requiring sophisticated motor planning and execution. Challenging the longstanding paradigm that emphasizes the dominance of the cerebral cortex1, our study highlights a pivotal role for spinal excitatory reflex circuits in both planning and executing skillful hand movements. Using a combination of experimental approaches with behaving non-human primates and predictive simulation, we identified a group of excitatory spinal interneurons that orchestrate a closed-loop, positive feedback mechanism during voluntary wrist movements. This mechanism is characterized by a bidirectional interaction between inter-neuronal spiking and muscle activity, mediated by motoneuronal efferent signals and proprioceptive afferent signals from the same agonistic muscles. Furthermore, we demonstrate that the temporal profile of muscle activity during movement execution, including amplitude and duration, is pre-determined during motor planning at the spinal interneurons, functioning as a force-feedback gain within the excitatory circuit. These findings suggest that autogenic spinal excitatory circuits play a predominant role in shaping overall muscle activation during motor execution, provided the proper reflex gain is pre-set by higher neural systems during motor planning. Together, our findings provide a cellular-level perspective on how spinal reflex loops contribute to skilled voluntary movements in primates, extending over a century of spinal reflex research2.

neuroscience↗

bioRxiv2025

Ubiquilin-2 liquid droplets catalyze α-synuclein fibril formation

Liquid-liquid phase separation (LLPS) and subsequent liquid-gel/solid transition are considered common aggregation mechanisms of proteins linked to neurodegenerative diseases. -synuclein (-syn), the main component of Parkinsons disease pathology, has been reported to undergo LLPS, thereby accelerating aggregate formation. However, the precise molecular events involved in the early stages of -syn aggregation remain controversial. In this study, we show that -syn aggregation is promoted by droplets formed by ubiquilin-2 (UBQLN2), rather than by -syn LLPS itself. During the liquid-gel/solid transition of UBQLN2 droplets, -syn within the droplets transformed into pathogenic fibrils both in vitro and in cells. Immunohistochemistry of brain sections from sporadic Parkinsons disease patients revealed UBQLN2 in substantia nigra Lewy bodies, implicating UBQLN2 in -syn aggregation in vivo. Furthermore, the small compound SO286 inhibited both UBQLN2 self-association and its interaction with -syn by binding to the STI1 domain, thereby suppressing -syn aggregation. These findings demonstrate that UBQLN2 droplets catalyze -syn fibrillization and suggest that small molecules targeting fibril-catalyzing proteins such as UBQLN2 may represent a novel therapeutic approach for neurodegenerative diseases.

biochemistry↗

bioRxiv2024

Spinal and cortical premotor control of primate dexterous hand movements

Skilled hand movements are an evolutionary advance in primates. Phylogenetically distinct corticospinal pathways are involved in hand control: "newer" direct corticomotoneuronal (CM) pathways and "older" indirect corticospinal pathways mediated by spinal premotor interneurons (PreM-INs). However, the functional differences of these pathways remain unclear. Here we show that CM cells and PreM-INs have distinct physiological properties for the activation of hand muscles and provide different types of movement control signals while monkeys perform a precision grip task. Spike-triggered averaging of electromyographic activity indicated that PreM-INs coactivate a larger number of muscles, whereas CM cells more selectively control fewer muscles. The firing activity of PreM-INs was tightly correlated with their target muscle activity and had a greater contribution to generating hand muscle activity. In contrast, CM cell activity diverged temporally from the target muscle activity and had a smaller contribution to its generation. On the basis of these results, we hypothesize that PreM-INs produce gross muscle activity by activating synergistic muscles, whereas CM cells fine-tune target muscle activity. This idea was supported by dimensional reduction analyses of hand muscle activity, as PreM-IN activity was specifically correlated with lower dimensional control of muscle activity, and CM cell activity was correlated with higher dimensional control. These results indicate that the two pathways have distinct functions, synergistic control and fine tuning of hand muscle activity, both of which are essential for the development of dexterous hand movement in primates.

neuroscience↗

bioRxiv2024

Proteomic analysis to classify extracellular vesicles and plasmodesmata in Arabidopsis cell culture supernatants

The plant apoplast contains diverse proteins. In this study, we analyzed the extracellular vesicle proteome using cell culture supernatants. Unexpectedly, many plasmodesmata proteins were identified in the extracellular vesicle fraction. The comparison between the cell culture EV proteome and the plasmodesmata proteome revealed that EV and plasmodesmata proteins were indistinguishable. Highly sensitive imaging analyses showed that PDLP3-GFP, a representative plasmodesmata marker, was localized to plasmodesmata, but it was also present as small granules in apoplast regions. Next, we attempted to distinguish EV proteins from plasmodesmata proteins. The step-wise density gradient ultracentrifugation and clustering analysis separated EV protein clusters (represented by tetraspanins and membrane trafficking proteins) from plasmodesmata clusters (represented by PDLPs and PDCBs). These results provide the basis for future explorations of plant plasmodesmata and EVs.

plant biology↗

bioRxiv2024

Time-course analysis of the transcriptome of Arabidopsis thaliana leaves under high-concentration ammonium sulfate treatment

Nitrogen is essential for plant growth and is sourced primarily from nitrate and ammonium in the soil. Even though plants can take ammonium up for nutrition, it often results in toxic effects such as growth suppression and chlorosis. To elucidate the mechanism of ammonium toxicity, a time-course analysis of the transcriptome was performed on A. thaliana leaves treated with high concentrations of ammonium sulfate in the presence of sufficient nitrate. The expression of nitrate-inducible genes tended to be downregulated by the treatment. The expression of genes relating to abscisic acid, jasmonic acid (JA), salicylic acid (SA), and membrane trafficking was upregulated, whereas that of photosynthesis-, auxin-, and cytokinin-related genes involved in growth and development was downregulated. The induction of many osmotic stress-responsive genes suggests the involvement of osmotic stress in ammonium toxicity. Furthermore, the upregulation of nitric oxide (NO)-inducible genes and the simultaneous upregulation of genes involved in JA biosynthesis, glutathione metabolism, and SA response suggested the involvement of endogenous NO and protein S-nitrosylation in response to high concentrations of ammonium sulfate. This study provides a novel and comprehensive overview of transcriptional changes occurring in response to high ammonium sulfate concentrations and proposes possible mechanisms of ammonium toxicity that can be explored in future research.

plant biology↗

bioRxiv2023

Global disinhibition and corticospinal plasticity for drastic recovery after spinal cord injury

The induction of large-scale plasticity in the adult brain should be key for recovery from severe damage of the central nervous system. Here, drastic motor recovery was observed after subhemisection spinal cord injury in macaques that received intensive training and cortical electrical stimulation. During recovery, movement-related activity increased in ipsilesional sensorimotor areas and functional connectivity from ipsilesional to contralesional areas was strengthened. Electrical stimulation applied widely across bilateral sensorimotor areas induced muscle twitches in affected and intact forelimbs. The interhemispheric inhibition observed before injury was switched to facilitation. Furthermore, massive re-routing occurred in corticospinal axons from the contralesional motor cortex. Such global disinhibition and massive plasticity would open the workspace for the reorganization of motor networks to recruit novel areas for recovery. One Sentence SummaryGlobal disinhibition and corticospinal plasticity for drastic recovery after spinal cord injury in macaque monkeys.

neuroscience↗

bioRxiv2021

Neural network models for spinal implementation of muscle synergies

Muscle synergies have been proposed as functional modules to simplify the complexity of body motor control; however, their neural implementation is still unclear. Converging evidence suggests that output projections of the spinal premotor interneurons (PreM-INs) underlie the formation of muscle synergies, but they exhibit a substantial variation across neurons and exclude standard models assuming a small number of unitary "modules" in the spinal cord. Here we compared neural network models for muscle synergies to seek a biologically plausible model that reconciles previous clinical and electrophysiological findings. We examined three neural network models: one with random connections (non-synergy model), one with a small number of spinal synergies (simple synergy model), and one with a large number of spinal neurons representing muscle synergies with a certain variation (population synergy model). We found that the simple and population synergy models emulate the robustness of muscle synergies against cortical stroke observed in human stroke patients. Furthermore, the size of the spinal variation of the population synergy matched well with the variation in spinal PreM-INs recorded in monkeys. These results suggest that a spinal population with moderate variation is a biologically plausible model for the neural implementation of muscle synergies.

neuroscience↗

bioRxiv2020

Causal roles of frontoparietal cortical areas in feedback control of the limb

Goal-directed motor corrections are surprisingly fast and complex, but little is known on how they are generated by the central nervous system. Here we show that temporary cooling of dorsal premotor cortex (PMd) or parietal area 5 (A5) in behaving monkeys caused impairments in corrective responses to mechanical perturbations of the forelimb. Deactivation of PMd impaired both spatial accuracy and response speed, whereas deactivation of A5 impaired spatial accuracy, but not response speed. Simulations based on optimal feedback control demonstrated that deactivation of the control policy (reduction of feedback gain) impaired both spatial accuracy and response speed, whereas deactivation in state estimation (reduction of Kalman gain) impaired spatial accuracy but not response speed, paralleling the impairments observed from deactivation of PMd and A5, respectively. Furthermore, combined deactivation of both cortical regions led to additive impairments of individual deactivations, whereas reducing the amount of cooling (i.e. milder cooling) to PMd led to impairments in response speed, but not spatial accuracy, both also predicted by the model simulations. These results provide causal support that higher order motor and somatosensory regions beyond primary somatosensory and primary motor cortex are involved in generating goal-directed motor responses. As well, the computational models suggest that the distinct patterns of impairments associated with these cortical regions reflect their unique functional roles in goal-directed feedback control.

neuroscience↗

bioRxiv2019

Distinct sensorimotor feedback loops for dynamic and static control of primate precision grip

Volitional limb motor control involves dynamic and static muscle actions. It remains elusive how such distinct actions are controlled through separated or shared neural circuits. Here we explored the potential separation for dynamic and static controls in the primate hand actions, by investigating the neuronal coherence between local 1eld potentials (LFPs) of the spinal cord and the forelimb electromyographic activity (EMGs), and LFPs of the motor cortex and the EMGs during the performance of a precision grip in macaque monkeys. We observed the emergence of beta-range coherence with EMGs at spinal cord and motor cortex in the separated phases; spinal coherence during the grip phase and cortical coherence during the hold phase. Further, both of the coherence were influenced by bidirectional interactions with reasonable latencies as beta oscillatory cycles. These results indicate that dedicated feedback circuits comprising spinal and cortical structures underlie dynamic and static controls of dexterous hand actions.

neuroscience↗

bioRxiv2019

Keep your hands apart: independent representations of ipsilateral and contralateral forelimbs in primary motor cortex

It is generally accepted that each cortical hemisphere primarily drives the opposite side of the body. Yet, primary motor cortical (M1) activity has been robustly correlated with both contralateral and ipsilateral arm movements. It has remained unanswered as to why ipsilaterally-related activity does not cause contralateral motor activity. Here we apply multi-joint elbow and shoulder loads to the left or right arms of monkeys during a postural perturbation task. We show that many M1 neurons respond to mechanical disturbances applied to either the contra- or ipsilateral arms. More neurons respond to loads applied to the contralateral arm with response magnitudes that were ~2x as large and had onset times that were ~10ms earlier. However, in some cases, neurons exhibited large and earlier responses to loads applied to the ipsilateral arm than loads applied to the contralateral arm. Similar effects were observed when the monkeys were maintaining postural control well after the load had been applied. Importantly, we show that the load preference to one arm has little predictive power on a neurons preference in the opposite arm. Furthermore, we found contralateral and ipsilateral neural activity resided in orthogonal subspaces allowing for a weighted sum of neural responses to extract the contralateral activity without interference from the ipsilateral activity, and vice versa. These data show how activity in M1 unrelated to downstream motor targets can be segregated from downstream motor output.

neuroscience↗

bioRxiv2018

Two distinct proprioceptive representations of voluntary movements in primate spinal neurons

When willingly setting our body in motion, we simultaneously know where and how our limbs are moving. While this indicates that proprioceptive information is readily represented in the neurons of the central nervous system, it is still unclear how. We recorded the activity of spinal neurons with direct projections from muscle spindle afferents in four monkeys, while they performed simple wrist movements. Against the assumption that these spinal neurons act as a simple relay of afferent input, we found the majority (56%) of neurons had firing patterns incongruent with a simple representation of spindle activity, and the minority had congruent patterns. Two groups of neurons showed distinct intrinsic characteristics (spike width, base firing rate and firing irregularity), and distinct control of their input-output gain. These results are the first demonstration that proprioceptive representation is achieved by the coordinated activity of distinct groups of neurons during volitional movement.

neuroscience↗