Biology subjects

Sakurai, Y.

Publications and source records attributed to Sakurai, Y..

17 recordsLinked to original sources

bioRxiv2026

Forward processing of spatiotemporal maps across hippocampal subfields in common marmosets

Episodic memory requires distinguishing similar events occurring at the same location but at different times. While the hippocampus integrates "where" and "when," the specific roles of the primate dentate gyrus (DG) and CA3 remain elusive. We recorded single-unit activity from freely moving marmosets navigating a spatial maze in a visually impoverished environment. Both hippocampal subfields robustly encoded self-position via neurons selective for stationary epochs at platforms and movement along trajectories, whereas gaze-related coding was minimal. While DG signaled stationary and dynamic self-positions independently, CA3 integrated these elements into conjunctive representations. Critically, only CA3 neurons exhibited strong temporal-order modulation. These findings reveal a feedforward disambiguation process in which CA3 transforms discrete spatial inputs from DG into the integrated spatiotemporal maps essential for episodic memory.

neuroscience↗

bioRxiv2026

An anti-aggregation region of the SGS3 N-terminal IDR is essential for secondary siRNA biogenesis

Secondary siRNA biogenesis amplifies small RNA signals from target transcripts and plays a pivotal role in plant development and defense responses. The RNA-binding protein SGS3 is essential for this pathway, recruiting RNA-dependent RNA polymerase 6 (RDR6) to Argonaute-small RNA-bound targets. The N-terminal intrinsically disordered region (IDR) of SGS3, which contains a prion-like domain (PrLD), has been reported to drive liquid-liquid phase separation, forming siRNA bodies, and to be required for secondary siRNA production. However, the molecular mechanism by which the N-terminal IDR contributes to secondary siRNA production remains unclear. Here, using in vitro reconstitution and in planta assays, we show that the N-terminal IDR comprises two functional modules: the PrLD and a negatively charged region (NCR). The PrLD is required for phase separation and siRNA body formation but is dispensable for secondary siRNA production. In contrast, mutations in the NCR caused SGS3 to form abnormally large cytoplasmic assemblies and markedly impaired secondary siRNA production. These results suggest that the N-terminal IDR helps maintain SGS3 in a functional, soluble state that supports efficient secondary siRNA biogenesis.

molecular biology↗

bioRxiv2025

Behavioral expression of decision confidence engages disentangled confidence coding in the orbitofrontal cortex

Task engagement is thought to recruit subsets of neurons encoding task-relevant variables, but it remains unclear whether it also reorganizes the geometry of population codes and how such reorganization supports behavior. Here we show that, in the orbitofrontal cortex (OFC), task engagement aligns population activity along a confidence axis, thereby enabling the behavioral use of decision confidence. We recorded OFC activity while rats performed two variants of the same perceptual decision-making task that differed only in reward-timing uncertainty, which altered the utility of post-decision confidence for guiding reward waiting. OFC neurons exhibited more linear responses to confidence when confidence was more strongly expressed in behavior. Although the proportion of OFC neurons encoding confidence was similar across strategies, strategy-dependent alignment of population activity to confidence emerged under variable long delays, and this alignment predicted confidence-based waiting behavior. These findings suggest that OFC population codes flexibly adapt to the behavioral relevance of task variables, linking cognitive strategy to the geometry of neural representation.

neuroscience↗

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.

neuroscience↗

bioRxiv2025

Boosting Antitumour Efficacy and Immunity by Boron Neutron Capture Therapy with Size-Controlled Nanoparticles

Boron neutron capture therapy (BNCT) is emerging cancer radiotherapy requiring 10B sensitizer. Although boronophenylalanine (BPA)-BNCT is approved clinically in Japan, the low tumour selectivity and retentivity result in the long-time infusion of high doses. Based on our finding of the size-controllable mechanochemical synthesis of boron-10 carbide nanoparticles (10B4C NPs), the 50 nm size NPs grafted with poly(glycerol), {superscript 1}BC(50)-PG, is found to show superior tumour selectivity and retentivity to enhance the eradication efficacy at much lower dosage (5 mg [10B] / kg (mouse)). The dosage is further reduced by twice neutron irradiation or combination with an immune checkpoint inhibitor (ICI). Antitumour immunity is found to be boosted by {superscript 1}BC(50)-PG-BNCT to induce abscopal effect to treat remote or metastatic tumours and long-term memory to prevent cancer recurrence. Additionally, minimal side effects and gradual NP excretion are observed for one year. The 10B4C(50)-PG is concluded to be a promising 10B carrier for clinical application of BNCT due to the prominent antitumour efficacy and immune-activation with minimal toxicity.

cancer biology↗

bioRxiv2024

Interval timing clock property in the rat granular retrosplenial cortex

The rodent granular retrosplenial cortex (gRSC), densely interconnected with the hippocampal formation and the anterior thalamic nuclei, plays an important role in learning and memory. We had revealed that small pyramidal neurons in the superficial layers of the rat gRSC exhibit late-spiking (LS) firing properties. It has been suggested that neural circuits containing LS neurons can encode time intervals on the order of seconds, known as "interval timing". To test the possibility that the rat gRSC is involved in the processing of interval timing, we employed a trace fear conditioning paradigm in which the conditioned stimulus (CS) and the unconditioned stimulus (US) were temporally separated. First, we examined the effect of cytotoxic lesions made in the RSC prior to trace fear conditioning. We found that intact rats exhibited freezing behavior after CS tone presentation, whereas lesioned rats did not exhibit such freezing behavior. Next, we conducted in vivo chronic or acute recordings of neural activity from the rat gRSC in a test session conducted one week after the conditioning. In both recordings, we observed a distinct spike activity in which there was a transient increase in the firing rate around the presentation of the CS tone, followed by a rapid suppression and then ramping activity (a gradual elevation of the firing rate) until the next CS presentation. This "ramping activity" is thought to be one way in which interval timing is represented in the brain. Post stimulus histogram analysis revealed the existence of ramping activity in the gRSC, which reached its peak at various time intervals after the onset of the CS tone. Interestingly, this activity was specifically observed in response to the CS tone but not to the non-CS tone. Moreover, in naive rat gRSC (no trace fear conditioning), no such ramping activity was observed. These results indicate that gRSC neurons can encode time information on the order of tens to hundreds of seconds, integrating incoming sensory input with past memory traces.

neuroscience↗

bioRxiv2023

Low blood concentration of alcohol enhances activity related to stopping failure in the right inferior frontal cortex

This study investigated the effects of low doses of alcohol, which are acceptable for driving a car, on inhibitory control and neural processing using the stop-signal task (SST) in 17 healthy right-handed social drinkers. The study employed simultaneous functional magnetic resonance imaging and electromyography (EMG) recordings to assess behavioural and neural responses under conditions of low-dose alcohol (breath-alcohol concentration of 0.15 mg/L) and placebo. The results demonstrated that even a small amount of alcohol consumption prolonged Go reaction times in the SST and modified stopping behaviour, as evidenced by a decrease in the frequency and magnitude of partial response EMG that did not result in button pressing during successful inhibitory control. Furthermore, alcohol intake enhanced neural activity during failed inhibitory responses in the right inferior frontal cortex, suggesting its potential role in behavioural adaptation following stop-signal failure. These findings suggest that even low levels of alcohol consumption within legal driving limits can greatly impact both the cognitive performance and brain activity involved in inhibiting responses. This research provides important evidence on the neurobehavioural effects of low-dose alcohol consumption, with implications for understanding the biological basis of impaired motor control and decision-making and potentially informing legal guidelines on alcohol consumption.

neuroscience↗

bioRxiv2023

An intra-oral flavor discrimination task in freely moving mice

Flavor plays a critical role in the pleasure of food. Flavor research has mainly focused on human subjects and revealed that many brain regions are involved in flavor perception. However, animal models for elucidating the mechanisms of neural circuits are lacking. Herein, we demonstrate the use of a novel behavioral task in which mice are capable of flavor discrimination. When the olfactory pathways of the mice were blocked, they could not perform the task. However, behavioral accuracy was not affected when the gustatory pathway was blocked by benzocaine. These results indicate that the mice performed this discrimination task mainly based on the intraoral flavor. We conclude that this novel task can contribute to research on the neural mechanisms of flavor perception.

neuroscience↗

bioRxiv2020

Encoding of odor information and reward anticipation in anterior cortical amygdaloid nucleus

Olfactory information directly reaches the amygdala through the olfactory cortex, without the involvement of thalamic areas, unlike other sensory systems. The anterior cortical amygdaloid nucleus (ACo) is one of the olfactory cortices that receives olfactory sensory input, and is part of the olfactory cortical amygdala, which relays olfactory information to the amygdala. To examine its electrophysiological features, we recorded individual ACo neurons during the odor-guided go/no-go task to obtain a water reward. Many ACo neurons exhibited odor-evoked go cue-preferred during the late phase of odor-sampling supporting the population dynamics that differentiate go/no-go responses before executing the odor-evoked behaviors. We observed two types of neurons with different anticipation signals: one neuron type exhibited gradual increases of activity toward reward delivery, while another type exhibited a phasic go cue-preferred activity during odor sampling as well as another phasic anticipatory activity for rewards. These results suggest that the ACo may be involved in reward-related behavioral learning by associating the olfactory information with reward anticipation.

neuroscience↗

bioRxiv2020

5-amino levulinic acid inhibits SARS-CoV-2 infection in vitro

The current COVID-19 pandemic requires urgent development of effective therapeutics. 5-amino levulinic acid (5-ALA) is a naturally synthesized amino acid and has been used for multiple purposes including as an anticancer therapy and as a dietary supplement due to its high bioavailability. In this study, we demonstrated that 5-ALA treatment potently inhibited infection of SARS-CoV-2, a causative agent of COVID-19. The antiviral effects could be detected in both human and non-human cells, without significant cytotoxicity. Therefore, 5-ALA is a candidate as an oral antiviral drug for COVID-19.

microbiology↗

bioRxiv2020

Bi-directional encoding of context-based odor signals and behavioral states by the nucleus of the lateral olfactory tract neurons

The nucleus of the lateral olfactory tract (nLOT) is not only a part of the olfactory cortex that receives olfactory sensory inputs from the olfactory bulb, but also one of the cortical amygdala areas that regulates motivational behaviors. To examine how the neural ensemble activity of the nLOT is modulated by motivational processes that occur during various states of learned goal-directed behaviors, we recorded nLOT spike activities of mice performing odor-guided go/no-go tasks for obtaining a water reward. We found that the majority of the nLOT neurons exhibited sharp go-cue excitation and persistent no-go-cue inhibition responses triggered by an odor onset. The bi-directional cue encoding introduced nLOT population response dynamics and provided a high odor decoding accuracy before executing cue-odor-evoked behaviors. The go-cue preferred neurons were also activated in the reward drinking state, indicating context-based odor-outcome associations. These findings suggest that the nLOT neurons play an important role in the translation from context-based odor information to appropriate behavioral motivation.

neuroscience↗

bioRxiv2020

Accurate perceptual decision driven by distinct population dynamics in association and sensory cortex

It is widely assumed that variability in visual detection performance is attributed to the fidelity of the visual responses in visual cortical areas, which could be modulated by fluctuations of internal states such as vigilance and behavioral history. However, it is not clear what neural ensembles represent such different internal states. Here, we utilized a visual detection task, which distinguishes perceptual states to identical stimuli, while recording neurons simultaneously from the primary visual cortex (V1) and the posterior parietal cortex (PPC). We found distinct population dynamics segregating hit responses from misses despite no clear differences in visual responses. The population-level computation was significantly contributed by heterogenous non-sensory neurons in V1, whereas the contribution from non-neurons with the previous outcome selectivity was prominent in PPC. These results indicate different contributions of non-sensory neurons in V1 and PPC for the population-level computation that enables behavioral responses from visual information.

neuroscience↗

bioRxiv2020

Roles of the ClC chloride channel CLH-1 in food-associated salt chemotaxis behavior of C. elegans

The ability of animals to process dynamic sensory information facilitates foraging in an ever changing environment. However, molecular and neural mechanisms underlying such ability remain elusive. The ClC anion channels/transporters play a pivotal role in cellular ion homeostasis across all phlya. Here we find a ClC chloride channel is involved in salt concentration chemotaxis of C. elegans. Genetic screening identified two altered-function mutations of clh-1 that disrupt experience-dependent salt chemotaxis. Using genetically encoded fluorescent sensors, we demonstrate that CLH-1 contributes to regulation of chloride and calcium dynamics of salt-sensing neuron, ASER. The mutant CLH-1 reduced responsiveness of ASER to salt stimuli in terms of both temporal resolution and intensity, which could disrupt navigation strategies for approaching preferred salt concentration. Furthermore, other ClC genes appeared to act redundantly in salt chemotaxis. These findings provide insights into the regulatory mechanism of neuronal responsivity by ClCs that contribute to modulation of navigation behavior.

genomics↗

bioRxiv2019

Dynamic coding of choice targets in the perirhinal cortex

Cortical neurons show distinct firing patterns across multiple task-epochs characterized by distinct computational aspects. Recent studies suggest that such distinct patterns underly dynamic population code achieving computational flexibility, whereas neurons in some cortical areas often show coherent firing patterns across epochs. To understand how such coherent single-neuron code contribute to dynamic population code, we analyzed neural responses in the perirhinal cortex (PRC) during cue and reward epochs of a two-alternative forced-choice task. We found that the PRC neurons often encoded the opposite choice-directions between those epochs. By using principal component analysis as population-level analysis, we identified neural subspaces associated with each epoch, which reflected coordinated patterns across the neurons. The cue and reward epochs shared neural dimensions where the choice directions were consistently discriminated. Interestingly, those dimensions were supported by dynamically changing contributions of individual neurons. These results indicated heterogeneity of coherent single-neuron responses in their contribution to population code.

neuroscience↗

bioRxiv2018

Tuning of ventral tenia tecta neurons of the olfactory cortex to distinct scenes of feeding behavior

Ventral tenia tecta (vTT) is a part of the olfactory cortex that receives both olfactory sensory signals from the olfactory bulb and top-down signals from the prefrontal cortex. To address the question whether and how the neuronal activity of the vTT is modulated by prefrontal cognitive processes such as attention, expectation and working memory that occurs during goal-directed behaviors, we recorded individual neuronal responses in the vTT of freely moving awake mice that performed learned odor-guided feeding and drinking behaviors. We found that the firing pattern of individual vTT cells had repeatable behavioral correlates such that the environmental and behavioral scene the mouse encountered during the learned behavior was the major determinant of when individual vTT neurons fired maximally. Furthermore, spiking activity of these scene cells was modulated not only by the present scene but also by the future scene that the mouse predicted. We show that vTT receives afferent input from the olfactory bulb and top-down inputs from the medial prefrontal cortex and piriform cortex.\n\nThese results indicate that different groups of vTT cells are activated at different scenes and suggest that processing of olfactory sensory information is handled by different scene cells during distinct scenes of learned feeding and drinking behaviors. In other words, during the feeding and drinking behavior, vTT changes its working mode moment by moment in accord with the scene change by selectively biasing specific scene cells. The scene effect on olfactory sensory processing in the vTT has implications for the neuronal circuit mechanisms of top-down attention and scene-dependent encoding and recall of olfactory memory.

neuroscience↗

bioRxiv2018

GABAergic neurons in the olfactory cortex projecting to the lateral hypothalamus in mice

Olfaction guides goal-directed behaviours including feeding. To investigate how central olfactory neural circuits control feeding behaviour in mice, we performed retrograde tracing from the lateral hypothalamus (LH), an important feeding centre. We observed a cluster of retrogradely labelled cells distributed in the posteroventral region of the olfactory peduncle. Histochemical analyses revealed that a majority of these retrogradely labelled projection neurons expressed glutamic acid decarboxylase 65/67 (GAD65/67), but not vesicular glutamate transporter 1 (VGluT1). We named this region with GABAergic projection neurons the ventral olfactory nucleus (VON) to discriminate it from the conventional olfactory peduncle. VON neurons were less immunoreactive for DARPP-32, a striatal neuron marker, in comparison to those in the olfactory tubercle and nucleus accumbens, which distinguished the VON from the ventral striatum. Fluorescent labelling confirmed synaptic contacts between VON neurons and olfactory bulb projection neurons. Rabies-virus-mediated trans-synaptic labelling revealed that VON neurons received synaptic inputs from the olfactory bulb, other olfactory cortices, horizontal limb of the diagonal band, and prefrontal cortex. Collectively, these results identified novel GABAergic projection neurons in the olfactory cortex that can integrate olfactory sensory and top-down inputs and send inhibitory output to the LH, which may contribute to forming odour-guided LH-related behaviours.

neuroscience↗

bioRxiv2017

Optimization-based synthesis of stochastic biocircuits with statistical specifications

Model-guided design has become a standard approach to engineering biomolecular circuits in current synthetic biology. However, the stochastic nature of biomolecular reactions is often overlooked in the design process. As a result, cell-cell heterogeneity causes unexpected deviation of biocircuit behaviors from model predictions and requires additional iterations of design-build-test cycles. To enhance the design process of stochastic biocircuits, this paper presents a computational framework to systematically specify the level of intrinsic noise using well-defined metrics of statistics and design highly heterogeneous biocircuits based on the specifications. Specifically, we use descriptive statistics of population distributions as an intuitive specification language of stochastic biocircuits and develop an optimization based computational tool that explores parameter configurations satisfying design requirements. Sensitivity analysis methods are also developed to ensure the robustness of a biocircuit design. These design tools are formulated using convex optimization programs to enable efficient and rigorous quantification of the statistics without approximation, and thus, they are amenable to the synthesis of stochastic biocircuits that require high reliability. We demonstrate these features by designing a stochastic negative feedback biocircuit that satisfies multiple statistical constraints. In particular, we use a rigorously quantified parameter map of feasible design space to perform in-depth study of noise propagation and regulation in negative feedback pathways.

synthetic biology↗