Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2025.11.29.691317

Head-Centred Sound Localisation Behaviour Reveals Head and World Centered Reference Frames in Auditory Cortex

Aghilli, N.·Town, S. M.·Bizley, J. K.
View original source ↗Export metadata ↓

Abstract

The auditory system relies on head-centered localisation cues to estimate sound source position. Yet listeners and single neurons can encode sound in world-centred spatial reference frames. However, most studies of sound localisation constrain the subjects orientation within a fixed speaker ring, making it difficult to distinguish which reference frame underlies spatial coding. We utilised a sound localisation task that required ferrets localise sound location, relative to the head, across rotations in the starting platform within the testing arena. Two ferrets were trained to discriminate front from back sounds. Once trained, the orientation of both the central platform and the target speakers were rotated between testing sessions, retaining the task contingency in head-centered coordinates, but breaking the alignment of head and world centered reference frames. Probe trials were presented from the other speakers so that spatial receptive fields could be constructed and compared across central platform rotations. Neural activity was recorded from auditory cortex using chronically implanted 32-channel arrays. Across 1,777 recorded units, 596 were stimulus driven. Spatially tuned neurons were predominantly head-centred, with 208 and 232 units classified as head-centred in the two animals, compared with 48 and 49 world-centred units and 33 and 26 un-tuned units, respectively. Temporal analysis showed that most units retained the same reference-frame classification from onset to offset, but the magnitude of their head-versus-world preference diminished over time, with offset responses shifting towards more ambiguous and, in some cases, world-centred coding. Together, these results demonstrate that auditory cortex maintains parallel head centered and allocentric representations that are head dominated at onset but incorporate increased world-centred information at offset, supporting perceptual constancy during dynamic listening.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Aghilli, N., Town, S. M., Bizley, J. K.. 2025-12-02. Head-Centred Sound Localisation Behaviour Reveals Head and World Centered Reference Frames in Auditory Cortex. https://doi.org/10.64898/2025.11.29.691317

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↗