Year: 2025
Type: article
Abstract: Sensory thresholds enable animals to regulate their behavioral responses to environmental threats. Despite the importance of sensory thresholds for animal behavior and human health, we do not yet have a full appreciation of the underlying molecular-genetic and circuit mechanisms. The larval zebrafish acoustic startle response provides a powerful system to identify molecular mechanisms underlying establishment of sensory thresholds and plasticity of thresholds through mechanisms like habituation. Using this system, we identify Cadherin-16 as a previously undescribed regulator of sensory gating. We demonstrate that Cadherin-16 regulates sensory thresholds via an endocrine organ, the corpuscle of Stannius (CS), which is essential in zebrafish for regulating Ca2+ homeostasis. We further show that Cadherin-16 regulates whole-body calcium and ultimately behavior through the hormone Stanniocalcin 1l (Stc1l), and the IGF-regulatory metalloprotease, Papp-aa. Finally, we demonstrate the importance of the CS through ablation experiments that reveal its role in promoting normal acoustic sensory gating. Together, our results uncover a previously undescribed brain non-autonomous pathway for the regulation of behavior and underscore Ca2+ homeostasis as a critical process underlying sensory gating in vivo.
Source: PLoS Biology
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,500
Funders: National Science Foundation, Boettcher Foundation, Cincinnati Children's Hospital Medical Center, Colorado State University, Johns Hopkins University, National Institutes of Health, University of Colorado Boulder, Anschutz Medical Campus, University of Colorado, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: G1027241741, G1086261101, G1466128636, G1556872922, G1664773227, G2316665, G337658256, Rocky Mountain Neurological Disorders Core Center, G5424111711, G6118902829, CC* Compute: HPC Services for the Colorado State University System, G7221159947, G7852733817, CC* Regional Computing: Enhancing Computing At Regional Schools in the Rocky Mountain Advanced Computing Consortium (RMACC), G8054170119, G8067353062, G9000046928, G9000104148, G9000126259, G9000203185, University of Colorado Anschutz Medical Campus DRC
OpenAlex ID: W4410025815