Biology subjects

Asari, H.

Publications and source records attributed to Asari, H..

14 recordsLinked to original sources

bioRxiv2026

Reciprocal feedback inhibition and divergent intrinsic firing properties between behaviorally defined classes of neurons in the mouse ventromedial hypothalamus

The capacity to orchestrate appropriate defensive behaviors in response to threatening stimuli is essential for the survival of organisms. Flight, freezing, appeasement, and attack, for example, are common defensive responses evoked depending upon the nature of the threat, the immediate context, and past experiences. Multiple brain regions have been implicated in regulating such responses, with the medial hypothalamus playing a key role in mediating innate responses to social and predator threats. The ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) has been shown to mediate both avoidance and aggression towards conspecific threats in mice, suggesting that it serves as a circuit for context-appropriate defensive responses to social threats. Previous in vivo calcium imaging in VMHvl identified cells whose activity encodes either approach toward or escape from a social threat (Assessment+ and Flight+ cells, respectively), but it remained unclear how the switch in neural encoding from approach to avoidance occurs. Here, we use in vivo single-unit electrophysiology recordings coupled to channelrhodopsin-assisted circuit mapping (optrodes) to explore the functional and structural connectivity basis of the approach-avoidance switch. We confirm the presence of Assessment+ and Flight+ neurons in VMHvl and demonstrate that they are interconnected through feedback excitation and reciprocal feedback inhibition. Moreover, we discover that Assessment+ and Flight+ neurons exhibit a pronounced difference in their intrinsic firing properties. We hypothesize that this asymmetry in intrinsic responsivity coupled to reciprocal feedback inhibition underlies the nonlinear firing changes at the approach-to-avoidance transition and plays a role in triggering escape behavior.

neuroscience↗

bioRxiv2025

The transcription of a single olfactory receptor per neuron is enforced by epigenetic silencing of their enhancers

The ability to discriminate thousands of odors in our environment requires each olfactory neuron to express a single olfactory receptor from hundreds of available genes. The biochemical mechanism enforcing this monogenic expression remains unknown. We show that deletion of the chromatin protein TRIM66 causes individual olfactory neurons to express multiple receptors at a high level, demonstrating that monogenic expression relies on an epigenetic silencing mechanism. Moreover, TRIM66 is specifically recruited to olfactory receptor gene super-enhancers during neuronal progenitor maturation, thereby silencing nearby olfactory receptor genes. Loss of monogenic expression disrupted axonal projections to the olfactory bulb, resulting in an aberrant topographic map and impaired social odor discrimination and reproductive behaviors. These findings uncover the chromatin-based silencing of super-enhancers as the mechanism underlying the organization of the mammalian olfactory system.

molecular biology↗

bioRxiv2025

Absence of Local Retinotopy in the Mouse Optic Tract

Retinotopy is a fundamental organizational principle of the visual system, where neighboring neurons represent adjacent points in visual space. This spatial relationship is established by precise anatomical wiring across successive areas, e.g., from the retina to the lateral geniculate nucleus (LGN) to the visual cortex. To examine the precision of this topographic arrangement within the long-range projection axons themselves, we recorded retinal ganglion cell (RGC) axons in the mouse optic tract (OT) and mapped their receptive fields (RFs). As expected for a retinotopically organized area, we found that nearby LGN cell pairs had significantly smaller RF distances than distant pairs. In contrast, no such relationship was observed among RGC axons in the OT. Modelling analyses further confirmed that the observed RF distances in the OT were incompatible with any locally retinotopic arrangement. Instead, the OT retained only coarse topography, with [~]18{degrees} RF deviations or [~]40 {micro}m axonal displacements from an ideal retinotopic organization. These results demonstrate that the mouse OT lacks fine-scale retinotopy and maintains only broad topographic structure.

neuroscience↗

bioRxiv2025

Column-Like Subnetwork Reconstruction in Motor Cortex from Graph-Based 3D High-Density Two-Photon Calcium Imaging

How precise 3D interactions among cortical neurons underlie layer-specific computations remains elusive. We developed a graph-framework to infer functional connectivity from fast volumetric two-photon Ca2+ imaging in the awake mouse primary motor cortex. By converting deconvolved traces into binary spike trains, removing population bursts, and applying an adaptive, layer-specific statistical threshold, we reconstructed a directed, weighted network of [~]1,000 neurons. Decomposition into strongly connected components revealed [~]10-cell subnetworks, predominantly in layer II/III but often bridging to layer Va. Across six 20-min recordings, we found that (1) layer II/III dominates connectivity, (2) feedback (Va[->]II/III) links are more numerous and stronger than the feed-forward (II/III[->]Va) ones, and (3) information flows in [≤] 6 synapses. We uncovered seven geometrical and dynamical motifs--ranging from compact columns to elongated diagonals--each with characteristic event sizes and durations. These findings reveal diverse, column-like microcircuits in M1 with a net ascending flow, suggesting that such subnetworks form elemental processing modules for motor control.

neuroscience↗

bioRxiv2025

Central infusion of prostaglandin E2 reveals a unified representation of sickness in the mouse insular cortex

During infections, vertebrates develop stereotypic symptoms such as elevated body temperature, reduced appetite, and lethargy. These changes, collectively known as sickness syndrome, are orchestrated by the brain in response to immune mediators released during systemic inflammation. While the roles of subcortical regions, including the hypothalamus and brainstem nuclei, in regulating sickness symptoms are well established, the contribution of the neocortex to the encoding and modulation of the sick state remains less well understood. We examined the neuronal correlates of sickness in the neocortex of awake mice following a single intracerebroventricular (i.c.v.) injection of prostaglandin E2 (PGE2), a well-characterized mediator of sickness. Behavioral analysis revealed that PGE2 elicited a rapid and robust sickness response, characterized by fever, slower locomotion, quiescence, anorexia, and eye squinting. Whole-brain Fos mapping showed that PGE2 generates a distinct neural activation pattern encompassing much of the interoceptive network. Electrophysiological recordings using Neuropixel probes in awake mice together with dimensionality reduction and decoding analysis revealed that neuronal population dynamics in the insular cortex (IC) and the primary somatosensory cortex (SSp), two regions involved in body state representation, encode sickness-related information, such as body temperature, walking velocity, grooming, and eye squinting. However, unlike SSp, ongoing neuronal activity in IC exhibited a better decoding performance for an integrated measure of sickness rather than individual symptoms. Together, these results suggest that PGE2 induces a coordinated physiological and behavioral response akin to a sick state, which is preferentially encoded in the IC.

neuroscience↗

bioRxiv2024

Sudden sensory events trigger modality-independent responses across layers in the mouse neocortex

Sudden sensory events trigger widespread electrocortical responses and noticeable changes in an animals behavior. It remains unclear, though, how this "surprise" signal is generated via afferent sensory input and represented by neuronal ensembles. Using in vivo electrophysiology, here we recorded the activity of different cortical areas across layers in awake head-fixed mice, while presenting sensory stimuli of different modalities and saliencies. When brief, salient stimuli were delivered at long intervals, we found prominent responses across cortical areas regardless of the stimulus modalities, resembling those observed in human electroencephalography. These responses were larger and emerged earlier in the infragranular layer than in the granular layer of the primary sensory cortex. At short inter-stimulus intervals, in contrast, only modality-specific responses were observed in the corresponding primary sensory cortex. These results indicate that sensory information travels through multiple ascending pathways, in particular, supra-modal surprise signals via non-classical sensory pathways to the cortex.

neuroscience↗

bioRxiv2024

Histamine interferes with the early visual processing in mice

Sensory processing is dynamically modulated by an animals behavior and internal states. Growing evidence suggests that such modulation starts from early stages, already at the retina, but the underlying mechanisms remain elusive. Combining pharmacological and chemogenetic tools with single-unit extracellular recordings in awake head-fixed mice, here we identified that the visual responses of retinal ganglion cells and the lateral geniculate nucleus were both made weaker and slower by histaminergic projections from the tuberomammillary nucleus of the posterior hypothalamus. The observed changes in the visual responses were, however, not directly linked with histaminergic modulation of pupil dynamics or locomotion behavior. Instead, our computational modelling analysis suggests that the temporal response modulations arise from changes in the intrinsic properties of the circuit, such as gain modulation via the histamine H1 receptors in the retina. Facilitation of visual processing at low histamine levels may offer an ethological advantage, enabling animals to respond rapidly to visual threats during periods of reduced activity.

neuroscience↗

bioRxiv2023

Atypical cortical feedback underlies failure to process contextual information in the superior colliculus of Scn2a+/- autism model mice

Atypical sensory integration and contextual learning are common symptoms in autism spectrum disorder (ASD), but how sensory circuits are affected remains elusive. Here we focused on the early visual information processing, and performed in vivo two-photon calcium imaging and pupillometry of mice engaged in an implicit learning task in stable and volatile visual contexts. Wild-type (WT) mice showed stimulus-specific contextual modulation of the visual responses in the superior colliculus (SC) and pupil dynamics, whereas Scn2a-haploinsufficient ASD-model mice exhibited abnormal modulation patterns. In both genotypes, feedforward inputs from the retina to SC demonstrated no such contextual modulation. In contrast, feedback inputs from the primary visual cortex (V1) showed modulation patterns similar to those of SC cells in WT mice, but no modulation in Scn2a+/- mice. Furthermore, chemogenetic perturbation revealed that this top-down signaling from V1 to SC mediated the observed contextual modulation both at the neurophysiological and behavioral levels. These results suggest that the corticotectal input is critical for contextual sensory integration in SC, and its anomaly underlies atypical sensory learning in ASD.

neuroscience↗

bioRxiv2022

Effective sound localization coding by noisy populations of mouse inferior colliculus neurons revealed by fast volumetric imaging

Sound location coding has been extensively studied at the central nucleus of the mammalian inferior colliculus (CNIC), supporting a population code. However, this population code has not been extensively characterized on the single-trial level with simultaneous recordings or at other anatomical regions like the dorsal cortex of inferior colliculus (DCIC), which is relevant for learning-induced experience dependent plasticity. To address these knowledge gaps, here we made in two complementary ways large-scale recordings of DCIC populations from awake mice in response to sounds delivered from 13 different frontal horizontal locations (azimuths): volumetric two-photon calcium imaging with [~]700 cells simultaneously recorded at a relatively low temporal resolution, and high-density single-unit extracellular recordings with [~]20 cells simultaneously recorded at a high temporal resolution. Independent of the method, the recorded DCIC population responses revealed substantial trial-to-trial variation (neuronal noise) which was significantly correlated across pairs of neurons (noise correlations) in the passively listening condition. Nevertheless, decoding analysis supported that these noisy response patterns encode sound location on the single-trial basis, reaching errors that match the discrimination ability of mice. The detected noise correlations contributed to minimize the error of the DCIC population code of sound azimuth. Altogether these findings point out that DCIC can encode sound location in a similar format to what has been proposed for CNIC, opening exciting questions about how noise correlations could shape this code in the context of cortico-collicular input and experience dependent plasticity.

neuroscience↗

bioRxiv2022

Retinotopic tiling of retinal ganglion cell axons at single-cell precision in the mouse superior colliculus

Retinotopy, like all long-range projections, can arise from the axons themselves or their targets. The underlying connectivity pattern, however, remains elusive at the fine scale in the mammalian brain. To address this question, we functionally mapped the spatial organization of the input axons and target neurons in the mouse retinocollicular pathway at single-cell resolution using in vivo two-photon calcium imaging. We found a near-perfect retinotopic tiling of retinal ganglion cell axon terminals, with an average error below 30 m or 2 degrees of visual angle. The precision of retinotopy was relatively lower for local neurons in the superior colliculus. Subsequent data-driven modelling ascribed it to a low input convergence, on average 5.5 retinal ganglion cell inputs to a postsynaptic cell in the superior colliculus. These results indicate that retinotopy arises largely from topographically precise input from presynaptic cells, rather than elaborating local circuitry to reconstruct the topography by postsynaptic cells.

neuroscience↗

bioRxiv2022

Awake responses suggest inefficient dense coding in the mouse retina

The structure and function of the vertebrate retina have been extensively studied across species with an isolated, ex vivo preparation. Retinal function in vivo, however, remains elusive, especially in awake animals. Here we performed single-unit extracellular recordings in the optic tract of head-fixed mice to compare the output of awake, anesthetized, and ex vivo retinas. While the visual response properties were overall similar across conditions, we found that awake retinal output had in general 1) faster kinetics with less variability in the response latencies; 2) a larger dynamic range; and 3) higher firing activity, by [~]20 Hz on average, for both baseline and visually evoked responses. Our modeling analyses further showed that such awake response patterns convey comparable total information but less efficiently, and allow for a linear population decoder to perform significantly better than the anesthetized or ex vivo responses. These results highlight distinct retinal behavior in awake states, in particular suggesting that the retina employs dense coding in vivo, rather than sparse efficient coding as has been often assumed from ex vivo studies.

neuroscience↗

bioRxiv2021

Sensory-thresholded switch of neural firing states in a computational model of the ventromedial hypothalamus

The mouse ventromedial hypothalamus (VMH) is both necessary and sufficient for defensive responses to predator and social threats. Defensive behaviors typically involve cautious approach toward potentially threatening stimuli aimed at obtaining information about the risk involved, followed by sudden avoidance and flight behavior to escape harm. In vivo neural recording studies in mice have identified two major populations of VMH neurons that either increase their firing activity as the animal approaches the threat (called Assessment+ cells) or increase their activity as the animal flees the threat (called Flight+ cells). Interestingly, Assessment+ and Flight+ cells abruptly decrease and increase their firing activity, respectively, at the decision point for flight, creating an escape-related "switch" in functional state. This suggests that the activity of the two cell types in VMH is coordinated and could result from local circuit interactions. Here, we used computational modelling to test if a local inhibitory feedback circuit could give rise to key features of the neural activity seen in VMH during the approach-to-flight transition. Starting from a simple dual-population inhibitory feedback circuit receiving repeated trains of monotonically increasing sensory input to mimic approach to threat, we tested the requirement for balanced sensory input, balanced feedback, short-term synaptic plasticity, rebound excitation, and inhibitory feedback exclusivity to reproduce an abrupt, sensory-thresholded reciprocal firing change that resembles Assessment+ and Flight+ cell activity seen in vivo. Our work demonstrates that a relatively simple local circuit architecture is sufficient for the emergence of firing patterns similar to those seen in vivo and suggests that a reiterative process of experimental and computational work may be a fruitful avenue for better understanding the functional organization of mammalian instinctive behaviors at the circuit level.

neuroscience↗

bioRxiv2021

Natural Image Statistics for Mouse Vision

The mouse has dichromatic color vision based on two different types of opsins: short (S)- and middle (M)-wavelength-sensitive opsins with peak sensitivity to ultraviolet (UV; 360 nm) and green light (508 nm), respectively. In the mouse retina, cone photoreceptors that predominantly express the S-opsin are more sensitive to contrasts and denser towards the ventral retina, preferentially sampling the upper part of the visual field. In contrast, the expression of the M-opsin gradually increases towards the dorsal retina that encodes the lower visual field. Such a distinctive retinal organization is assumed to arise from a selective pressure in evolution to efficiently encode the natural scenes. However, natural image statistics of UV light remain largely unexplored. Here we developed a multi-spectral camera to acquire high-quality UV and green images of the same natural scenes, and examined the optimality of the mouse retina to the image statistics. We found that the local contrast and the spatial correlation were both higher in UV than in green for images above the horizon, but lower in UV than in green for those below the horizon. This suggests that the dorsoventral functional division of the mouse retina is not optimal for maximizing the bandwidth of information transmission. Factors besides the coding efficiency, such as visual behavioral requirements, will thus need to be considered to fully explain the characteristic organization of the mouse retina.

neuroscience↗

bioRxiv2020

Feedback from retinal ganglion cells to the inner retina

Retinal ganglion cells (RGCs) are thought to be strictly postsynaptic within the retina. They carry visual signals from the eye to the brain, but do not make chemical synapses onto other retinal neurons. Nevertheless, they form gap junctions with other RGCs and amacrine cells, providing possibilities for RGC signals to feed back into the inner retina. Here we identified such feedback circuitry in the salamander and mouse retinas. First, using biologically inspired circuit models, we found mutual inhibition among RGCs of the same type. We then experimentally determined that this effect is mediated by gap junctions with amacrine cells. Finally, we found that this negative feedback lowers RGC visual response gain without affecting feature selectivity. The principal neurons of the retina therefore participate in a recurrent circuit much as those in other brain areas, not being a mere collector of retinal signals, but are actively involved in visual computations.

neuroscience↗