Biology subjects

Hirokawa, J.

Publications and source records attributed to Hirokawa, J..

10 recordsLinked to original sources

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

Pharmacological potentiation of Nav1.1 channels in interneurons mitigates tau depositions and neuronal death in a mouse model of neurodegenerative dementias

Epileptiform discharges and neuronal hyperexcitability are key pathophysiological features of Alzheimers disease and related tauopathies. We previously identified selective dynfuntion of parvalbumin-positive GABAergic interneurons (PV neurons), which regulate neural network excitability, in a tauopathy mouse model. However, the mechanistic link between PV neuron deficits, tau pathology, and neurodegeneration remains unclear. Here, we demonstrate that pharmacological enhancement of phasic PV neuron activity markedly attenuates tau accumulation and neuronal loss in a tauopathy mouse model. We developed DSR-143630, a novel activator of voltage-gated sodium channel Nav1.1, selectively expressed in PV neurons. Administration of DSR-143630 alleviated febrile seizures in Nav1.1 haploinsufficient mice and suppressed high-frequency oscillations (HFOs), an electrophysiological signature of hyperexcitability associated with cognitive impairments, in rTg4510 tau transgenic mice. Longitudinal tau PET and volumetric MRI demonstrated that DSR-143630 treatment from 4 to 11 months of age profoundly reduced age-dependent tau deposition and atrophy in the neocortex and hippocampus. Postmortem analyses further revealed decreased levels of phosphorylated tau, preservation of neuronal populations, and attenuated neuroinflammatory responses, including reactive gliosis. These findings establish PV neuron dysfunctions and consequent network hyperexcitability as key drivers of tau pathogenesis and highlight pharmacological Nav1.1 activation as a promising disease-modifying strategy for neurodegenerative tauopathies. One Sentence SummaryPharmacological potentiation of interneuronal activities attenuates aberrant network excitability, progressive tau deposition, and neurodegeneration.

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

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.

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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.

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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↗

bioRxiv2017

Analysis of ipsilateral corticocortical connectivity in the mouse brain

In primates, proximal cortical areas are interconnected via within-cortex \"intrinsic\" pathway, whereas distant areas are connected via \"extrinsic\" white matter pathway. It is not well known how cortical areas are interconnected in small-brained mammals like rodents. In this study, we systematically analyzed the data of Allen Mouse Brain Connectivity Atlas to answer this question and found that the ipsilateral cortical connections in mice are almost exclusively contained within the grey matter with the exception of the retrosplenial area. We analyzed the layer-specific distribution of axonal projections within the grey matter using Cortical Box method and obtained the following results. First, widespread axonal projections were observed in both upper and lower layers in the vicinity of injections, whereas highly specific \"point-to-point\" projections were observed toward remote areas. Second, such long-range projections were predominantly aligned in the anteromedial-posterolateral direction. Third, in majority of these projections, the connecting axons traveled through layer 6. Finally, the projections from the primary and higher order areas to distant targets preferentially terminated in the middle and superficial layers, respectively, suggesting hierarchical connections similar to those of primates. Overall, our study suggests the conserved nature of neocortical organization across species despite conspicuous differences in wiring strategy.

neuroscience↗

bioRxiv2017

Categorical Representations Of Decision-Variables In Orbitofrontal Cortex

The brain creates internal representations of the external world in the form of neural activity, which is structured to support adaptive behavior. In many cortical regions, individual neurons respond to specific features that are matched to the function of each region and statistics of the world. In frontal cortex, however, neurons display baffling complexity, responding to a mixture of sensory, motor and other variables. Here we use an integrated new approach to understanding the architecture of higher-order cortical representations, and use this approach to show that discrete groups of orbitofrontal cortex (OFC) neurons encode distinct decision variables. Using rats engaged in a complex task combining perceptual and value guided decisions, we found that OFC neurons can be grouped into distinct, categorical response types. These categorical representations map directly onto decision-variables of a choice model explaining our behavioral data, such as reward size, decision confidence and integrated value. We propose that, like sensory neurons, frontal neurons form a sparse and over complete population representation aligned to the natural statistics of the world - in this case spanning the space of decision-variables required for optimal behavior.

neuroscience↗