Biology subjects

Imai, F.

Publications and source records attributed to Imai, F..

9 recordsLinked to original sources

bioRxiv2026

Global context rapidly shapes sensory responses in V1

Context modulates sensory processing in the cerebral cortex by suppressing responses to expected stimuli and enhancing responses to unexpected ones. Recent proposals argue that early sensory areas such as primary visual cortex (V1) are shaped only by local context, including recent stimulus history, whereas modulation by global context, such as learned temporal structure, is present exclusively in higher cortical areas. This view is incompatible with predictive coding theories. To directly dissociate local and global contextual influences, we used a global/local oddball paradigm in which mice viewed five-item sequences. Across conditions, sequence structure was held constant while stimulus identity and predictability were selectively manipulated, allowing the isolation of response modulations due to local deviance, global expectation, and stimulus repetition independently. In the canonical sequence (AAAA-B), B is locally deviant but globally predictable. Using two-photon calcium imaging and LFP recordings in mouse V1, we found that global predictability abolished context modulation: responses to B were equivalent to those evoked by a random sequence control (e.g., CDEAB). This effect emerged rapidly, after only <10 sequence repetitions, demonstrating fast learning of global structure. When the stimulus was globally deviant, either by replacing B with a novel stimulus (AAAA-C) or by presenting B unpredictably in a standard oddball paradigm, V1 exhibited robust response enhancement. These effects required feedback from anterior cingulate area (ACa), establishing a causal role for higher cortical circuits in conveying global predictions to V1. Strikingly, when an additional A replaced B (AAAA-A), responses were strongly suppressed despite global deviance, indicating that stimulus-specific adaptation may constrain the expression of global prediction error signals in early sensory cortex. HighlightsGlobal context rapidly modulates neural responses in V1 Global deviations, but not predictable local deviants, elicit enhanced responses Downstream brain region ACa is necessary for global context modulation in V1 Standard oddball paradigms involve higher-order contextual modulation

neuroscience↗

bioRxiv2025

Mismatch negativity develops in adolescence and independently of microglia

Higher brain functions and cognition undergo a critical period of development during adolescence, when psychiatric disorders such as schizophrenia typically onset. Understanding how developmental processes during adolescence interact with schizophrenia pathophysiology and risk remains a central goal in psychiatry. Here we show that a well-established biomarker of schizophrenia, mismatch negativity, matures during adolescence in mouse primary visual cortex, along with a strengthening of fronto-visual functional connectivity. Because microglia are implicated in schizophrenia risk and disease states, we further investigated what role microglia may play in the development of mismatch responses under physiological conditions. We found that microglial depletion with PLX5622 in adolescence arrests the development of resting oscillations in frontal areas, but does not affect the development of deviance detection, other signatures of visual context processing, or prefrontal-visual functional connectivity. Our findings suggest (a) a key component of mismatch negativity develops in adolescence, a period of vulnerability to schizophrenia, and (b) the development underlying this component does not require robust microglia activity, clarifying the developmental role of microglia in higher order visual processing.

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bioRxiv2025

The common neural representation in the primary motor area between motor execution and kinesthetic motor imagery

Although motor imagery activates higher-order motor-related areas, the role of the primary motor area (M1) in motor imagery remains unclear. This study aimed to investigate whether motor imagery recruits a neural representation of fingers similar to that of motor execution in the hand M1. Ten healthy right-handed adults executed and kinesthetically imagined tapping using one of four fingers. Using functional magnetic resonance imaging with multi-voxel pattern analysis, we trained the decoder to classify which finger the participants were moving using brain activation during motor execution and tested whether it could predict which finger the participants were imaging to move during motor imagery (cross-classification). We also performed the classification in the reverse direction. The average accuracy of these cross-classifications was significantly higher than chance in the left hemisphere hand M1 (hand-M1). Analysis of the representational geometry showed that the distance of neural representations for the same fingers was statistically shorter than that for different fingers between motor execution and imagery. Furthermore, we conducted a replication study with 14 participants and found results similar to those of the original study. Our results suggest that the neural representation of kinesthetic motor imagery is partially similar to that of motor execution in the contralateral hand M1.

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bioRxiv2024

Anatomical and functional analysis of the corticospinal tract in an FRDA mouse model

Friedreichs ataxia (FRDA) is one of the most common hereditary ataxias. It is caused by a GAA repeat in the first intron of the FXN gene, which encodes an essential mitochondrial protein. Patients suffer from progressive motor dysfunction due to the degeneration of mechanoreceptive and proprioceptive neurons in dorsal root ganglia (DRG) and cerebellar dentate nucleus neurons, especially at early disease stages. Postmortem analyses of FRDA patients also indicate pathological changes in motor cortex including in the projection neurons that give rise to the cortical spinal tract (CST). Yet, it remains poorly understood how early in the disease cortical spinal neurons (CSNs) show these alterations, or whether CSN/CST pathology resembles the abnormalities observed in other tissues affected by FXN loss. To address these questions, we examined CSN driven motor behaviors and pathology in the YG8JR FRDA mouse model. We find that FRDA mice show impaired motor skills, exhibit significant reductions in CSN functional output, and, among other pathological changes, show abnormal mitochondrial distributions in CSN neurons and CST axonal tracts. Moreover, some of these alterations were observed as early as two months of age, suggesting that CSN/CST pathology may be an earlier event in FRDA disease than previously appreciated. These studies warrant a detailed mechanistic understanding of how FXN loss impacts CSN health and functionality.

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bioRxiv2024

Layer Va neurons, as major presynaptic partners of corticospinal neurons, play critical roles in skilled movements

Corticospinal neurons (CSNs) are located in the cortex and projecting into the spinal cord. The activation of CSNs, which is associated with skilled motor behaviors, induces the activation of interneurons in the spinal cord. Eventually, motor neuron activation is induced by corticospinal circuits to coordinate muscle activation. Therefore, elucidating how the activation of CSNs in the brain is regulated is necessary for understanding the roles of CSNs in skilled motor behaviors. However, the presynaptic partners of CSNs in the brain remain to be identified. Here, we performed transsynaptic rabies virus-mediated brain-wide mapping to identify presynaptic partners of CSNs (pre-CSNs). We found that pre-CSNs are located in all cortical layers, but major pre-CSNs are located in layer Va. A small population of pre-CSNs are also located outside the cortex, such as in the thalamus. Inactivation of layer Va neurons in Tlx3-Cre mice results in deficits in skilled reaching and grasping behaviors, suggesting that, similar to CSNs, layer Va neurons are critical for skilled movements. Finally, we examined whether the connectivity of CSNs is altered after spinal cord injury (SCI). We found that unlike connections between CNSs and postsynaptic neurons, connections between pre-CSNs and CSNs do not change after SCI.

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bioRxiv2024

Forelimb motor recovery by modulating extrinsic and intrinsic signaling as well as neuronal activity after the cervical spinal cord injury

Singular strategies for promoting axon regeneration and motor recovery after spinal cord injury (SCI) have been attempted with limited success. Here, we propose the combinatorial approach of deleting extrinsic and intrinsic factors paired with neural stimulation, will enhance adaptive axonal growth and motor recovery after SCI. We previously showed the deletion of RhoA and Pten in corticospinal neurons inhibits axon dieback and promotes axon sprouting after lumbar SCI. Here, we examined the effects of RhoA;Pten deletion coupled with neural stimulation after cervical SCI. This combinatorial approach promoted more boutons on injured corticospinal neurons in the spinal cord compared to sole RhoA;Pten deletion. Although RhoA;Pten deletion does not promote motor recovery in the forelimb after SCI, stimulating corticospinal neurons in those mice results in partial motor recovery. These results demonstrate that a combinatorial approach that pairs genetic modifications with neuronal stimulation can promote axon sprouting and motor recovery following SCI.

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bioRxiv2024

Human sensorimotor cortex reactivates recent visuomotor experience during awake rest

Previous studies have suggested that awake rest after training is helpful in improving motor performance and memory consolidation in visuomotor learning. Re-emergence of task-related activation patterns during awake rest has been reported, which play a role in memory consolidation or perceptual learning. This study aimed to test whether such reactivation occurs after visuomotor learning in the primary sensorimotor cortex. During fMRI scanning, 42 normal participants learned visuomotor tracking, while a rotational perturbation was introduced between a cursor position and a joystick angle. This visuomotor learning block was interleaved with the control block, during which the participants passively viewed a replay of previously performed cursor movements of their own. Half of the participants used their right hand, and the other half used their left hand to control the joystick. The resting-state scans were measured before and after the visuomotor learning sessions. A multivariate pattern classifier was trained to classify task and control blocks and then tested with resting scans before and after learning. Results revealed a significant increase in the number of volumes classified as the task in the post-learning rest compared with the pre-learning, indicating a re-emergence of task-related activities. Representational similarity analysis also showed a more similar pattern of activity with the task during the post-learning rest period. Furthermore, this effect is specific to the primary sensorimotor cortex contralateral to the hand used and significantly correlated with motor improvement after rest. Our finding revealed the reactivation of task-related patterns in the primary sensorimotor cortex for offline visuomotor learning. Significance StatementPrevious research suggests that awake rest after learning promotes memory consolidation, which is subserved by the re-emergence of task-specific activity patterns. We aimed to determine whether such reactivation occurs in the primary sensorimotor cortex following visuomotor learning for offline memory consolidation. Our results showed a significant increase in task-classified brain volumes during the post-learning rest period compared to the pre-learning period, indicating a re-emergence of task-related activity. Furthermore, this effect was specific to the primary sensorimotor cortex contralateral to the hand used for the task and significantly correlated with the motor performance following the rest period. These findings provide evidence for the reactivation of task-related patterns during offline visuomotor learning, which may underlie memory consolidation processes.

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bioRxiv2024

The Dorsal Column Nuclei Scales Mechanical Allodynia During Neuropathic Pain

Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to the brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading to the perception of touch as pain, known as mechanical allodynia. Two main drivers of peripheral tactile information, low-threshold mechanoreceptors (LTMRs) and postsynaptic dorsal column neurons (PSDCs), terminate in the brainstem dorsal column nuclei (DCN). Activity within the DRG, spinal cord, and DCN have all been implicated in mediating allodynia, yet the DCN remains understudied at the cellular, circuit, and functional levels compared to the other two. Here, we show that the gracile nucleus (Gr) of the DCN mediates tactile sensitivity for low-threshold stimuli and contributes to mechanical allodynia during neuropathic pain in mice. We found that the Gr contains local inhibitory interneurons in addition to thalamus-projecting neurons, which are differentially innervated by primary afferents and spinal inputs. Functional manipulations of these distinct Gr neuronal populations resulted in bidirectional changes to tactile sensitivity, but did not affect noxious mechanical or thermal sensitivity. During neuropathic pain, silencing Gr projection neurons or activating Gr inhibitory neurons was able to reduce tactile hypersensitivity, and enhancing inhibition was able to ameliorate paw withdrawal signatures of neuropathic pain, like shaking. Collectively, these results suggest that the Gr plays a specific role in mediating hypersensitivity to low-threshold, innocuous mechanical stimuli during neuropathic pain, and that Gr activity contributes to affective, pain-associated phenotypes of mechanical allodynia. Therefore, these brainstem circuits work in tandem with traditional spinal circuits underlying allodynia, resulting in enhanced signaling of tactile stimuli in the brain during neuropathic pain.

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bioRxiv2023

Neural substrates of top-down processing during perceptual duration-based timing and beat-based timing

Temporal context is a crucial factor in timing. Previous studies have revealed that the timing of regular stimuli, such as isochronous beats or rhythmic sequences (termed beat-based timing), activated the basal ganglia, whereas the timing of single intervals or irregular stimuli (termed duration-based timing) activated the cerebellum. We conducted a functional magnetic resonance imaging (fMRI) experiment to determine whether top-down processing of perceptual duration-based and beat-based timings affected brain activation patterns. Our participants listened to auditory sequences containing both single intervals and isochronous beats and judged either the duration of the intervals or the tempo of the beats. Whole-brain analysis revealed that both duration judgments and tempo judgments activated similar areas, including the basal ganglia and cerebellum, with no significant difference in the activated regions between the two conditions. In addition, an analysis of the regions of interest revealed no significant differences between the activation levels measured for the two tasks in the basal ganglia as well as the cerebellum. These results suggested that a set of common brain areas were involved in top-down processing of both duration judgments and tempo judgments. Our findings indicate that perceptual duration-based timing and beat-based timing are driven by stimulus regularity irrespective of top-down processing.

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