bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.09.29.510116

Development shaped by cue reliability in the barn owl's auditory midbrain

Shadron, K. K.·Pena, J. L.
View original source ↗Export metadata ↓

Abstract

Sensory systems display capability to preferentially choose stimuli based on their reliability at conveying accurate information. While previous reports have shown the ability of the brain to reweigh cues based on ongoing or dynamic changes in reliability, how the brain may learn and maintain neural responses to sensory statistics expected to be stable over longer time periods remain significant open questions of potential mechanisms underlying naturalistic biased perception. This study provides evidence that the barn owls midbrain is shaped by permanent statistics experienced during development. The barn owls midbrain features a topographic map of auditory space where neurons compute horizontal sound location from the interaural time difference (ITD). Previous work has shown that frequency tuning of these midbrain map neurons is correlated with the pattern of most reliable frequencies for the neurons preferred ITD. This pattern of ITD reliability is due to the filtering properties of the head, primarily determined by the facial ruff in the barn owl. In this study, we found that the absence of a facial ruff led to a decrease in the reliability of high frequencies originating from frontal space. To test if the owls frequency tuning of midbrain map neurons is driven by permanent changes in the pattern of ITD reliability, these neurons were recorded from adult owls, who had the facial ruff removed as juveniles, and from juvenile owls, before the facial ruff developed. In both groups, we found that frontally-tuned neurons displayed tunings to frequencies lower than reported in normal adult owls, consistent with the difference in ITD reliability between the normal and ruff removed conditions. Juvenile owls also exhibited more heterogeneous frequency tuning, suggesting developmental processes that refine tuning to match the pattern of ITD reliability. Additional recordings immediately upstream of the midbrain map displayed ITD tuned neural responses for all frequencies across the owls normal hearing range. Broader analysis of the effects of ruff-removal on the acoustical properties of spatial cues indicated a dominant role of ITD reliability in driving the adaptive changes in frequency tuning. These results support the hypothesis that frequency tuning in the midbrain map is developmentally adapted to permanent statistics of spatial cues, implementing probabilistic coding for sound localization.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Shadron, K. K., Pena, J. L.. 2022-09-29. Development shaped by cue reliability in the barn owl's auditory midbrain. https://doi.org/10.1101/2022.09.29.510116

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗
bioRxiv2026

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗
bioRxiv2026

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗