Biology subjects

Osako, Y.

Publications and source records attributed to Osako, Y..

17 recordsLinked to original sources

bioRxiv2026

Eye-specific drive and binocular suppression in mouse visual cortex during critical period development

A key function of cortical sensory circuits is to integrate information from multiple sources to build a unified representation of the external environment. The binocular region of the mouse primary visual cortex (bV1) is a valuable model for studying sensory integration, as visual response properties of inputs from the contralateral (contra) and ipsilateral (ipsi) eye onto bV1 neurons become matched to one another over development. While the alignment of visual responses from each eye during this developmental critical period has been well-characterized, it remains unclear how this interocular alignment influences, and is influenced by, the binocularly driven responses of bV1 neurons. Here, we recorded the monocular and binocular visual response properties of layer 2/3 bV1 neurons by performing chronic two-photon calcium imaging at multiple time points spanning the ocular-dominance critical period. We found that ipsi driven responses strengthened in bV1 neurons alongside a concurrent increase in binocular suppression. Binocular tuning properties were more strongly aligned with contra responses than with ipsi responses throughout development but became progressively better matched to ipsi responses. Additionally, the explained variance of ipsi input to predicting binocular tuning increased. In chronically tracked bV1 neurons, the preferred orientation of ipsi eye driven responses was less stable than that of contra eye driven responses, and in well-tuned stable binocular neurons, ipsi and contra preferences became progressively better matched. Using population-based decoding analyses, we found that while monocular and binocular visual encoding remained stable, there was increased generalizability between visual encoding by binocular and ipsi eye driven responses. Overall, our data suggest a reciprocal interaction between ipsi development and binocular responses, such that ipsi visual inputs dynamically structure excitatory as well as putative inhibitory drive onto binocular neurons during the critical period to generate the circuitry that implements integrated binocular vision.

neuroscience↗

bioRxiv2026

Parallel processing of orthogonal manifolds enables zero-shot composition in recurrent networks

Animals flexibly combine learned behaviors into novel actions without practicing their combinations, yet the computational mechanisms that enable independently acquired computations to be expressed in parallel remain unclear. Here we show that feedback geometry during learning determines whether recurrent dynamics can be recombined through zero-shot parallel composition. Using recurrent networks trained by a local predictive plasticity rule, we found that distinct feedback vectors embed independently learned computations in separable dynamical subspaces, allowing novel input combinations to co-activate these components and generate composite outputs without joint training. In contrast, aligned feedback vectors, as well as networks trained by backpropagation through time, exhibited accurate single-task performance but failed to support parallel composition, demonstrating that task acquisition and future reusability are dissociable properties of learning. A combined input evoked a single composite population trajectory, whose projections onto feedback-shaped task subspaces recovered the independently learned component dynamics. The same principle reproduced additive reach-posture geometry observed in motor cortex and generalized to higher-dimensional movement primitives. These results identify feedback geometry as a computational principle by which learning systems structure recurrent dynamics for future compositional reuse.

neuroscience↗

bioRxiv2026

Internal state dynamically gates task-specific attractor dynamics in prefrontal cortex

Internal states such as motivation and task engagement influence cognitive functions. Working memory, which maintains information over time, is an essential component of cognition and is modulated by motivation. Here, we show motivational states modulated attractor dynamics that supported working memory. Combining population recordings from mouse medial prefrontal cortex (mPFC) with data-constrained recurrent neural network (RNN) modeling, we found task engagement selectively modulated attractor dynamics within a memory-maintenance subspace, while stimulus-evoked responses remained intact. Reverse-engineering the RNNs revealed that task engagement reorganized the dynamical landscape by stabilizing memory-specific attractors. Specifically, task engagement modulated interactions between neurons to change the attractor dynamics. Finally, gradual changes in behavioral engagement were predicted by continuous modulation of attractor geometry in RNNs and mPFC. Together, these results suggest that internal state modulate working memory function by controlling the dynamical regime of mPFC circuits, providing a mechanistic link between internal state, neural dynamics, and cognitive function.

neuroscience↗

bioRxiv2026

Learning sculpts orthogonal task manifolds for continual skill learning in recurrent networks

Humans and animals can learn and seamlessly perform a vast repertoire of behaviors. However, how neural populations incorporate new skills without disrupting previously learned ones remains poorly understood. This challenge is known as catastrophic forgetting in artificial neural networks and is especially severe in recurrent networks, where computation relies on stable internal dynamics. While current machine learning approaches often rely on explicit weight-protection strategies, such approaches do not directly address this challenge. Here we show that orthogonal task manifolds can emerge in recurrent neural networks from a local predictive, error-driven learning rule. Our model preserves task-specific latent dynamics that remain resilient to interference from subsequent learning. Using low-rank connectivity ablations, we causally isolate these latent dynamics, selectively impairing individual tasks while leaving others intact. We further show that the proposed principle generalizes beyond low-dimensional to high-dimensional naturalistic movie replay, suggesting a scalable mechanism for continual learning. Our results identify a solution to catastrophic forgetting by preserving previously learned dynamics in recurrent connectivity, thereby providing a mechanistic bridge between artificial recurrent networks and biological neural circuits.

neuroscience↗

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

Reusable modular architecture enables flexible cognitive operations

Complex behaviors are thought to be built by combining simpler cognitive components. Computational modeling has shown that artificial neural networks can perform a variety of tasks by flexibly combining functional modules, each specialized for a specific computation, to construct a complex task. However, it is unknown whether reusable modular networks are found in the brain. Here, we show that mice performing a delayed match-to-sample with delayed report (DMS-dr) task reuse neuronal subspaces that were specialized for stimulus processing and memory maintenance. These subspaces were reused during the task to represent new stimulus inputs and different types of memories, respectively. Clustering analyses showed each subspace was supported by a distinct cluster of neurons in prefrontal cortex and parietal cortex. Studying artificial recurrent networks constrained to neural data found silencing specific clusters disrupted specific computations, consistent with a modular and reusable organization. Altogether, our findings show that the brain can flexibly reuse computational components to perform a complex cognitive task.

animal behavior and cognition↗

bioRxiv2024

Sensory History Drives Adaptive Neural Geometry in LP/Pulvinar-Prefrontal Cortex Circuits

Prior expectations guide attention and support perceptual filtering for efficient processing during decision-making. Here we show that during a visual discrimination task, mice use prior stimulus history to guide ongoing choices by estimating differences in evidence between consecutive trials (|{Delta}Dir|). The thalamic lateral posterior (LP)/pulvinar nucleus provides robust inputs to the Anterior Cingulate Cortex (ACC), which has been implicated in selective attention and predictive processing, but the function of the LP-ACC projection is unknown. We found that optogenetic manipulations of LP-ACC axons disrupted animals ability to effectively estimate and use information across stimulus history, leading to |{Delta}Dir|-dependent biases. Two-photon calcium imaging of LP-ACC axons revealed an engagement-dependent low-dimensional organization of stimuli along a curved manifold. This representation was scaled by |{Delta}Dir| in a manner that emphasized greater deviations from prior evidence. Thus, our work identifies the LP-ACC pathway as essential for selecting and evaluating stimuli relative to prior evidence to guide decisions.

neuroscience↗

bioRxiv2024

Astrocytic modulation of population encoding in mouse visual cortex via GABA transporter 3 revealed by multiplexed CRISPR/Cas9 gene editing

Astrocytes, which are increasingly recognized as pivotal constituents of brain circuits governing a wide range of functions, express GABA transporter 3 (Gat3), an astrocyte-specific GABA transporter responsible for maintenance of extra-synaptic GABA levels. Here, we examined the functional role of Gat3 in astrocyte-mediated modulation of neuronal activity and information encoding. First, we developed a multiplexed CRISPR construct applicable for effective genetic ablation of Gat3 in the visual cortex of adult mice. Using in vivo two-photon calcium imaging of visual cortex neurons in Gat3 knockout mice, we observed changes in spontaneous and visually driven single neuronal response properties such as response magnitudes and trial-to-trial variability. Gat3 knockout exerted a pronounced influence on population-level neuronal activity, altering the response dynamics of neuronal populations and impairing their ability to accurately represent stimulus information. These findings demonstrate that Gat3 in astrocytes profoundly shapes the sensory information encoding capacity of neurons and networks within the visual cortex.

neuroscience↗

bioRxiv2024

Cortical norepinephrine-astrocyte signaling critically mediates learned behavior

Updating behavior based on feedback from the environment is a crucial means by which organisms learn and develop optimal behavioral strategies1-3. Norepinephrine (NE) release from the locus coeruleus (LC) has been shown to mediate learned behaviors4-6 such that in a task with graded stimulus uncertainty and performance, a high level of NE released after an unexpected outcome causes adaptations in subsequent behavior7. Yet, how the transient activity of LC-NE neurons, lasting tens of milliseconds, alters neuronal activity and influences behavior several seconds later is unclear. Here, we show that NE released after an unexpected outcome acts directly on cortical astrocytes via 1 adrenergic (Adra1a) receptors to elicit sustained increases in intracellular calcium. Chemogenetic blockade of astrocytic calcium dynamics prevents trial-to-trial behavioral adaptation. NE stimulation of astrocytes elicits ATP release, and imaging ATP levels in the cortex reveals an increase in extracellular ATP in response to an unexpected outcome. Blocking ATP-driven signaling to neuronal adenosine A1 receptors also prevents post-reinforcement behavioral adaptation. Finally, high density neuronal recordings in prefrontal cortex reveal that a surprising outcome alters the neuronal representation of the stimulus on the subsequent trial without sustained changes in cortical activity; blocking either astrocyte calcium dynamics or A1 receptors occludes these post-reinforcement changes in single-neuron and population neuronal encoding of task variables underlying behavioral changes. Together, these data demonstrate that astrocytes play an essential role in norepinephrine-driven learned behavior: they have prolonged calcium responses to transient norepinephrine release and convey task-relevant reinforcement information across behavioral intervals, enabling selective updating of neuronal task representations to support adaptive behavior.

neuroscience↗

bioRxiv2024

Early differential impact of MeCP2 mutations on functional networks in Rett syndrome patient-derived human cerebral organoids

Human cerebral organoids derived from induced pluripotent stem cells can recapture early developmental processes and reveal changes involving neurodevelopmental disorders. Mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene are associated with Rett syndrome, and disease severity varies depending on the location and type of mutation. Here, we focused on neuronal activity in Rett syndrome patient-derived organoids, analyzing two types of MeCP2 mutations - a missense mutation (R306C) and a truncating mutation (V247X) - using calcium imaging with three-photon microscopy. Compared to isogenic controls, we found abnormal neuronal activity in Rett organoids and altered network function based on graph theoretic analyses, with V247X mutations impacting functional responses and connectivity more severely than R306C mutations. These changes paralleled EEG data obtained from patients with comparable mutations. Labeling DLX promoter-driven inhibitory neurons demonstrated differences in activity and functional connectivity of inhibitory and excitatory neurons in the two types of mutation. Transcriptomic analyses revealed HDAC2-associated impairment in R306C organoids and decreased GABAA receptor expression in excitatory neurons in V247X organoids. These findings demonstrate mutation-specific mechanisms of vulnerability in Rett syndrome and suggest targeted strategies for their treatment.

bioengineering↗

bioRxiv2024

Prefrontal Cortex subregions provide distinct visual and behavioral feedback modulation to the Primary Visual Cortex

The mammalian Prefrontal Cortex (PFC) has been suggested to modulate sensory information processing across multiple cortical regions via long-range axonal projections. These axonal projections arise from PFC subregions with unique brain-wide connectivity and functional repertoires, which may provide the architecture for modular feedback intended to shape sensory processing. Here, we used axonal tracing, axonal and somatic 2-photon calcium imaging, and chemogenetic manipulations in mice to delineate how projections from the Anterior Cingulate Cortex (ACA) and ventrolateral Orbitofrontal Cortex (ORB) of the PFC modulate sensory processing in the primary Visual Cortex (VISp) across behavioral states. Structurally, we found that ACA and ORB had distinct patterning of projections across cortical regions and layers, monosynaptically targeting both excitatory and inhibitory neuronal cell types in these areas. ACA axons in VISp had a stronger representation of visual stimulus information than ORB axons, but both projections showed non-visual, behavior-dependent activity. ACA input to VISp enhanced the encoding of visual stimuli by VISp neurons, and modulation of visual responses scaled with arousal. On the other hand, ORB input shaped movement and arousal related modulation of VISp visual responses, but surprisingly reduced the encoding of high-contrast visual stimuli. Thus, ACA and ORB feedback have separable projection patterns and encode distinct visual and behavioral information, putatively providing the substrate for their unique effects on visual representations and behavioral modulation in VISp. Our results offer a refined model of cortical hierarchy and its impact on sensory information processing, whereby specific PFC projections contribute uniquely to VISp activity during discrete behavioral states.

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↗

bioRxiv2023

Emotional association enhances perceptual memory through amygdalo-cortical inputs during NREM sleep

Emotional arousal is thought to enhance the consolidation of associated memories by activating the basolateral amygdala (BLA) and its projections to memory-storing regions1-4. Although the importance of both rapid eye movement (REM) and non-REM (NREM) sleep-state specific BLA activity for emotional memory processing has been proposed5-9, how and when the BLA interacts with other brain regions to enhance memory consolidation remains unclear10. Here, by adding emotional information to a perceptual recognition task that relies on top-down inputs from frontal to sensory cortices, we demonstrated that the BLA not only associates emotional information with perceptual information, but also enhances the retention of associated perceptual memory through BLA-frontal projections. Electrophysiological recordings revealed that emotional association increases the reactivation of coordinated activity across the BLA-frontal-sensory region during NREM sleep, but not during REM sleep. Notably, this inter-regional coordinated reactivation during NREM sleep was entrained to the BLA high-frequency oscillations in the emotional condition, suggesting that the BLA triggers inter-regional interaction. Optogenetic silencing of BLA terminals in the frontal cortex during NREM sleep, but not REM sleep, disrupted the enhanced retention of the perceptual memory, but not the association itself or the emotional component of associative memory. Our results indicate that the inter-regional coordination through the BLA-cortical inputs during NREM sleep is causally required for memory enhancement by emotional arousal.

neuroscience↗

bioRxiv2021

Reward priming differentially modulates enhancement and inhibition in auditory decision-making

In cognitive sciences, rewards, such as money and food, play a fundamental role in individuals daily lives and well-being. Moreover, rewards that are irrelevant to the task alter individuals behavior. However, it is unclear whether explicit knowledge of reward irrelevancy has an impact on reward priming enhancements and inhibition. In this study, an auditory change-detection task with task-irrelevant rewards was introduced. The participants were informed explicitly in advance that the rewards would be given randomly. The results revealed that while inhibition related to reward priming only occurred when the participants were explicitly informed about rewards, implicit instruction thereof resulted in enhancement and inhibition associated with reward priming. These findings highlight the contribution of explicit information about rewards associated with auditory decisions.

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↗

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

Temporal dynamics of endogenous attentional modulation without cue awareness

Invisible visual stimuli can regulate our broad cognitive performance in the pursuit of current goals. Endogenous spatial attention is an important modulator of cognitive performance, and it can be triggered by unconscious cues. However, how its effect changes with time remains unclear. Here, we show that endogenous attention was triggered by an arrow-cue whose direction participants reported being unaware of but which affected the task performance in a time-dependent manner. Participants were asked to remember the directions of eight Landolt c rings (target memory array) after arrow-cue presentation, which was designed to orient their attention to a certain c ring. Then, we applied a delay, ranging from 83 ms to 1000 ms, between the arrow-cue and the target memory array presentation (the possible delays were equally spaced on a logarithmic scale). The attentional effect was greater for the 83, 183, 250 and 333 ms delays than the other six possible delays. In contrast, its effect was maintained irrespective of the delay when the participants reported being aware of the cue direction. Thus, awareness of arrow-cue direction was necessary to maintain endogenous attentional modulation, and its modulation without arrow-cue direction awareness was limited in a time-dependent manner.

neuroscience↗