Biology subjects

Tsukano, H.

Publications and source records attributed to Tsukano, H..

8 recordsLinked to original sources

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

Orthogonal spectral and temporal envelope representation in auditory cortex

Speech perception relies on two fundamental acoustic components: spectral and temporal. While spectral information is known to be represented in the auditory cortex through tonotopy, how temporal features are organized has remained unclear. Here, by varying rise-ramp steepness and frequencies, we reveal that the steepness of the temporal envelope--a critical cue for phonemes discrimination and sound source perception--is systematically mapped in the mouse auditory cortex. Using widefield calcium imaging, we discovered that the envelope steepness is represented orthogonally to the tonotopic axis, forming a two-dimensional cortical map that mirrors the dual structure of sounds. This organization was observed in primary-like auditory regions but not in higher-order-like areas, indicating distinct auditory processing streams. These findings uncover a principle of cortical organization, suggesting that the auditory cortex encodes sound along two independent axes and thereby provides a neural basis for parallel processing for complex sounds such as speech and natural acoustic environments.

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↗

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↗

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↗

bioRxiv2019

Reciprocal connectivity between secondary auditory cortical field and amygdala in mice

Recent studies have examined the feedback pathway from the amygdala to the auditory cortex in conjunction with the feedforward pathway from the auditory cortex to the amygdala. However, these connections have not been fully characterized. Here, to visualize the comprehensive connectivity between the auditory cortex and amygdala, we injected cholera toxin subunit b (CTB), a bidirectional tracer, into multiple subfields in the mouse auditory cortex after identifying the location of these subfields using flavoprotein fluorescence imaging. After injecting CTB into the secondary auditory field (A2), we found densely innervated CTB-positive axon terminals that were mainly located in the lateral amygdala (La), and slight innervations in other divisions such as the basal amygdala. Moreover, we found a large number of retrogradely-stained CTB-positive neurons in La after injecting CTB into A2. When injecting CTB into the primary auditory cortex (A1), a small number of CTB-positive neurons and axons were visualized in the amygdala. Finally, we found a near complete absence of connections between the other auditory cortical fields and the amygdala. These data suggest that reciprocal connections between A2 and La are main conduits for communication between the auditory cortex and amygdala in mice.

neuroscience↗

bioRxiv2017

Thalamocortical Projectional Divergence Leads to Complexity in Functional Organizations in Mouse Auditory Cortex

Frequency-related topological projections from the ventral division of the medial geniculate body (MGv) relay the tonotopic organization found in primary auditory cortex (A1). However, relaying circuits of the functional organization to higher-order, secondary auditory field (A2) have not been identified so far. Here, using tracing, we found that A2 receives dense topological projections from MGv in mice, and that tonotopy was established in A2 even when primary fields including A1 were removed. These indicate that thalamic inputs to A2 are sufficient for generating its tonotopy. Moreover, neuronal responses in the thalamocortical recipient layer of A2 showed wider bandwidth and greater heterogeneity of the best frequency distribution than those of A1, which was attributed to larger divergence of thalamocortical projections from MGv to A2 than those from MGv to A1. The current study identifies that the functional organization in the auditory cortex can be determined by the structure of thalamocortical input.\n\nSignificant StatementAlthough peripheral input patterns to the primary auditory cortex (A1) of the brain are well understood, how tonal information is relayed to higher-order regions such as the secondary auditory field (A2) remains unclear. This work revealed a new source of auditory information to A2; the tonal map in mouse A2 is primarily produced by orderly projections from the primary auditory thalamus. We also found that the complex behaviour and organization of neurons in A2 is generated by divergent projections from the primary thalamus that converge on neurons in A2. Our findings indicate that thalamocortical projections constitute a major factor that determines the regional properties and functional organization of mouse A2.

neuroscience↗