Biology subjects

Kline, A. M.

Publications and source records attributed to Kline, A. M..

5 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↗

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↗

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↗