Biology subjects

Kato, H. K.

Publications and source records attributed to Kato, H. K..

9 recordsLinked to original sources

bioRxiv2026

Ascending inputs to inferior colliculus subdivisions reveal pathway-specific hybrid organization in the external cortex

The inferior colliculus (IC) is a major hub of the auditory system, integrating ascending inputs from auditory and non-auditory brainstem nuclei before relaying information to the thalamus, and ultimately, the cortex. The IC is classically divided into the central nucleus (CIC) and surrounding shell regions, including the external (ECIC) and dorsal (DCIC) cortices. Although numerous tracing studies have described ascending inputs to the IC, most have either treated the IC as a uniform structure or distinguished only core and shell regions, leaving potential heterogeneity within the shell unresolved. Here, we performed retrograde tracing from distinct subdivisions of the mouse IC to compare their ascending input organization. By systematically targeting the CIC, DCIC, and both rostral and caudal ECIC and registering labeled neurons to a standardized brain atlas, we quantified input neurons across auditory and non-auditory brainstem structures. The CIC exhibited input patterns largely consistent with canonical pathways. In contrast, the DCIC received greater input from paralemniscal, periolivary, and non-auditory nuclei. Notably, the ECIC did not simply receive DCIC-like inputs or occupy an intermediate position between CIC and DCIC. Instead, it displayed a pathway-specific hybrid organization: inputs from the nuclei of the lateral lemniscus and superior olivary complex were largely CIC-like, whereas inputs from the cochlear nucleus and non-auditory regions resembled those of the DCIC. Furthermore, rostral and caudal ECIC showed overlapping but distinct input patterns. Together, these results reveal heterogeneous ascending connectivity across IC subdivisions and identify the ECIC as a hybrid interface that bridges CIC-like and DCIC-like ascending pathways. Significance StatementThe inferior colliculus is often divided into a lemniscal core and nonlemniscal shell, but whether shell subdivisions share a common ascending input organization has not been directly tested. By systematically mapping ascending inputs to the central nucleus, dorsal cortex, and rostral and caudal external cortex, we show that the shell regions are not uniform. Instead, the external cortex combines core-like inputs from the nuclei of the lateral lemniscus and the superior olivary complex with dorsal cortex-like inputs from the cochlear nucleus and non-auditory regions. These findings revise the classical core-versus-shell framework and provide an anatomical basis for parallel midbrain pathways, in which the external cortex is positioned for fast auditory signaling while simultaneously receiving contextual and multisensory modulation.

neuroscience↗

bioRxiv2026

Large cranial windows distort sensory maps and degrade feature integration in higher-order cortex

Understanding how sensory information is transformed along cortical hierarchies requires reliable measurement of sensory representations across areas. In vivo two-photon calcium imaging through chronic cranial windows has become an essential approach for characterizing cortical sensory representations with cellular resolution and spatial registration across experiments. However, cortical computations, particularly in higher-order cortices, depend on intricate intracortical circuitry and can be sensitive to subtle tissue perturbations introduced during surgical preparation. Here, we report that implantation of large cranial windows can mechanically compress the intrinsically curved cortical surface, producing systematic distortion that is usually not recognized as overt tissue damage. By comparing sensory maps in the mouse auditory cortex before and after window implantation, we show that larger windows commonly used across laboratories are associated with distorted sensory maps away from the center of the window. Furthermore, both macroscopic and cellular-level imaging reveal a deterioration of feature-selective responses in the secondary auditory cortex (A2) following such distortion. Together, these findings identify an overlooked but controllable surgical factor that can bias measurements of sensory representations and highlight an important consideration for enhancing reproducibility across studies.

neuroscience↗

bioRxiv2025

Noncanonical Short-Latency Auditory Pathway Directly Activates Deep Cortical Layers

Auditory processing in the cerebral cortex is considered to begin with thalamocortical inputs to layer 4 (L4) of the primary auditory cortex (A1). In this canonical model, A1 L4 inputs initiate a hierarchical cascade, with higher-order cortices receiving pre-processed information for the slower integration of complex sounds. Here, we identify alternative ascending pathways in mice that bypass A1 and directly reach multiple layers of the secondary auditory cortex (A2), indicating parallel activation of these areas alongside sequential information processing. We found that L6 of both A1 and A2 receive short-latency (<10 ms) sound inputs, comparable in speed to the canonical A1 L4 input but transmitted through higher-order thalamic nuclei. Additionally, A2 L4 is innervated by a caudal subdivision within the traditionally defined primary thalamus, which we now identify as belonging to the non-primary system. Notably, both thalamic regions receive projections from distinct subdivisions of the higher-order inferior colliculus, which in turn are directly innervated by cochlear nucleus neurons. These findings reveal alternative ascending pathways reaching A2 at L4 and L6 via secondary subcortical structures. Thus, higher-order auditory cortex processes both slow, pre-processed information and rapid, direct sensory inputs, enabling parallel and distributed processing of fast sensory information across cortical areas.

neuroscience↗

bioRxiv2024

Predictive filtering of sensory response via orbitofrontal top-down input

Habituation is a crucial sensory filtering mechanism whose dysregulation can lead to a continuously intense world in disorders with sensory overload. While habituation is considered to require top-down predictive signaling to suppress irrelevant inputs, the exact brain loci storing the internal predictive model and the circuit mechanisms of sensory filtering remain unclear. We found that daily neural habituation in the primary auditory cortex (A1) was reversed by inactivation of the orbitofrontal cortex (OFC). Top-down projections from the ventrolateral OFC, but not other frontal areas, carried predictive signals that grew with daily sound experience and suppressed A1 via somatostatin-expressing inhibitory neurons. Thus, prediction signals from the OFC cancel out behaviorally irrelevant anticipated stimuli by generating their "negative images" in sensory cortices.

neuroscience↗

bioRxiv2023

Distinct nonlinear spectrotemporal integration in primary and secondary auditory cortices

Animals sense sounds through hierarchical neural pathways that ultimately reach higher-order cortices to extract complex acoustic features, such as vocalizations. Elucidating how spectrotemporal integration varies along the hierarchy from primary to higher-order auditory cortices is a crucial step in understanding this elaborate sensory computation. Here we used two-photon calcium imaging and two-tone stimuli with various frequency-timing combinations to compare spectrotemporal integration between primary (A1) and secondary (A2) auditory cortices in mice. Individual neurons showed mixed supralinear and sublinear integration in a frequency-timing combination-specific manner, and we found unique integration patterns in these two areas. Temporally asymmetric spectrotemporal integration in A1 neurons enabled their discrimination of frequency-modulated sweep directions. In contrast, temporally symmetric and coincidence-preferring integration in A2 neurons made them ideal spectral integrators of concurrent multifrequency sounds. Moreover, the ensemble neural activity in A2 was sensitive to two-tone timings, and coincident two-tones evoked distinct ensemble activity patterns from the linear sum of component tones. Together, these results demonstrate distinct roles of A1 and A2 in encoding complex acoustic features, potentially suggesting parallel rather than sequential information extraction between these regions.

neuroscience↗

bioRxiv2022

Biological constraints on stereotaxic targeting of functionally-defined cortical areas

Understanding computational principles in hierarchically organized sensory systems requires functional parcellation of brain structures and their precise targeting for manipulations. Although brain atlases are widely used to infer area locations in the mouse neocortex, it has been unclear whether stereotaxic coordinates based on standardized brain morphology accurately represent functional domains in individual animals. Here, we used intrinsic signal imaging to evaluate the accuracy of area delineation in the atlas by mapping functionally-identified auditory cortices onto bregma-based stereotaxic coordinates. We found that auditory cortices in the brain atlas correlated poorly with the true complexity of functional area boundaries. Inter-animal variability in functional area locations predicted surprisingly high error rates in stereotaxic targeting with atlas coordinates. This variability was not simply attributed to brain sizes or suture irregularities but instead reflected differences in cortical geography across animals. Our data thus indicate that functional mapping in individual animals is essential for dissecting cortical area-specific roles with high precision.

neuroscience↗

bioRxiv2022

Prepronociceptin-expressing neurons in the extended amygdala signal darting away from an aversive odor

Dysregulation in the neural circuitry that encodes physiological arousal responses is thought to contribute to the manifestation of the maladaptive behaviors observed in neuropsychiatric disorders. We previously found that prepronociceptin-expressing neurons in the bed nucleus of the stria terminalis (PnocBNST neurons) modulate rapid changes in physiological arousal upon presentation of motivationally salient stimuli (Rodriguez-Romaguera et al., 2020). However, whether PnocBNST neurons are necessary to regulate behavioral actions to motivationally salient stimuli is still unknown. Here, we investigated the role of PnocBNST neurons in encoding behavioral responses to motivationally salient stimuli using in vivo calcium imaging and optogenetic approaches in freely behaving mice. We find that the bulk activity of PnocBNST neurons increases when mice are near an aversive odor in comparison to a rewarding odor. However, optogenetic inhibition of PnocBNST neurons does not affect the amount of time mice spend near an aversive odor. Further analysis revealed that a subgroup of PnocBNST neurons that correlate with proximity to the aversive odor also correlate to darting away from the same aversive odor. Since these two behaviors are opposite to each other and since we previously found PnocBNST neurons correlate with arousal responses, we believe these results may be due in part to the encoding of arousal responses that occur when mice approach and dart away from aversive stimuli.

neuroscience↗

bioRxiv2022

Translaminar Recurrence from Layer 5 Suppresses Superficial Cortical Layers

Information flow in the sensory cortex has been described as a predominantly feedforward sequence with deep layers as the output structure. Although recurrent excitatory projections from layer 5 (L5) to superficial L2/3 have been identified by anatomical and physiological studies, their functional impact on sensory processing remains unclear. Here, we use layer-selective optogenetic manipulations in the primary auditory cortex to demonstrate that feedback inputs from L5 suppress the activity of superficial layers, contrary to the prediction from their excitatory connectivity. This suppressive effect is predominantly mediated by translaminar circuitry through intratelencephalic (IT) neurons, with an additional contribution of subcortical projections by pyramidal tract (PT) neurons. Furthermore, L5 activation sharpened tone-evoked responses of superficial layers in both frequency and time domains, indicating its impact on cortical spectro-temporal integration. Together, our findings challenge the classical view of feedforward cortical circuitry and reveal a major contribution of inhibitory recurrence in shaping sensory representations.

neuroscience↗

bioRxiv2021

Inhibitory Gating of Coincidence-Dependent Sensory Binding in Secondary Auditory Cortex

Integration of multi-frequency sounds into a unified perceptual object is critical for recognizing syllables in speech. This "feature binding" relies on the precise synchrony of each components onset timing, but little is known regarding its neural correlates. We find that multi-frequency sounds prevalent in vocalizations, specifically harmonics, preferentially activate the mouse secondary auditory cortex (A2), whose response deteriorates with shifts in component onset timings. The temporal window for harmonics integration in A2 was broadened by inactivation of somatostatin-expressing interneurons (SOM cells), but not parvalbumin-expressing interneurons (PV cells). Importantly, A2 has functionally connected subnetworks of neurons encoding harmonic, but not inharmonic sounds. These subnetworks are stable across days and exist prior to experimental harmonics exposure, suggesting their formation during development. Furthermore, A2 inactivation impairs performance in a discrimination task for coincident harmonics. Together, we propose A2 as a locus for harmonic integration, which may form the circuit basis for vocal processing.

neuroscience↗