Biology subjects

Brann, D. H.

Publications and source records attributed to Brann, D. H..

5 recordsLinked to original sources

bioRxiv2026

TEX15 safeguards neuronal diversity in the mouse olfactory system

Animals detect diverse chemicals using hundreds of chemoreceptor proteins. In many organisms, sensory chemoreceptors obey a one-receptor-type-per-cell rule, which organizes information gathered by sensory neurons. A key question remains how receptor expression gets diversified so that hundreds of chemoreceptors get expressed across the population of sensory neurons. Here we show that diverse odorant receptor (OR) expression in mice requires testis expressed gene 15 (Tex15). We find that Tex15 regulates OR expression in neuronal precursor cells. In Tex15 deficient (Tex15-/-) mice, OR transcript levels are increased in precursors, a handful of early-transcribed OR genes get expressed at abnormally high levels, and these ORs come to dominate the olfactory sensory neuron population. This results in a profound reduction in the diversity of OR gene choice as well as disrupted spatial patterning of the olfactory epithelium, without disrupting the one-receptor-type-per-cell rule. Tex15 encodes a transcriptional repressor, and we show that Tex15-/- mice have reduced heterochromatin-associated H3K9me3 on OR genes. Thus, we propose that Tex15 directs a heterochromatin-based transcriptional repression mechanism that prevents uneven transcriptional onset from skewing OR choice. This mechanism safeguards the cellular diversity that is essential for broadly tuned chemosensation.

genomics↗

bioRxiv2025

A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain

Although topographical maps organize many peripheral sensory systems, it remains unclear whether olfactory sensory neurons (OSNs) choose which of the [~]1100 odor receptors (ORs) to express based upon their spatial location in the olfactory epithelium (OE) or instead ORs are scattered randomly. Here we reveal that each OR is expressed at a precise mean position along the OE dorsoventral axis, thereby instantiating a receptor map. This patterning reflects the differential use, by precursors and mature OSNs, of a coherent gene expression program controlled by a spatially-varying retinoic acid gradient; this program -- which includes key transcription factors and axon guidance genes -- translates position into a spatially appropriate distribution of OR choices and aligns the epithelial map of OR identity with the glomerular map present in the olfactory bulb. These results identify a transcriptional code that distinguishes and spatially organizes the vast array of sensory channels that comprise the olfactory system.

neuroscience↗

bioRxiv2025

3D spatial transcriptomics reveals the molecular domain structure of the mouse olfactory bulb

A core organizing principle of the vertebrate brain is its symmetry along multiple axes. However, the precision with which neurons, circuit modules, and brain regions align to these axes remains poorly understood. Here, we used 3D spatial transcriptomics to reconstruct the anatomical and molecular organization of the mouse olfactory bulb. We mapped the positions of nearly one thousand molecularly distinct glomeruli, the structural and functional units of odor processing, revealing highly symmetric organization across hemispheres. Within each bulb, we delineated a curved axis of symmetry that divides pairs of sister glomeruli. Gene expression in the olfactory epithelium predicted glomerular position with near-glomerular resolution. However, glomerular symmetry did not extend to deeper layer mitral and granule cells, suggesting a reorganization from sensory input to cortical output pathways. Our findings provide the first comprehensive map of the olfactory bulb and reveal how its molecular structure is instructed by epithelial gene expression programs.

neuroscience↗

bioRxiv2022

Persistent post-COVID-19 smell loss is associated with inflammatory infiltration and altered olfactory epithelial gene expression

Most human subjects infected by SARS-CoV-2 report an acute alteration in their sense of smell, and more than 25% of COVID patients report lasting olfactory dysfunction. While animal studies and human autopsy tissues have suggested mechanisms underlying acute loss of smell, the pathophysiology that underlies persistent smell loss remains unclear. Here we combine objective measurements of smell loss in patients suffering from post-acute sequelae of SARS-CoV-2 infection (PASC) with single cell sequencing and histology of the olfactory epithelium (OE). This approach reveals that the OE of patients with persistent smell loss harbors a diffuse infiltrate of T cells expressing interferon-gamma; gene expression in sustentacular cells appears to reflect a response to inflammatory signaling, which is accompanied by a reduction in the number of olfactory sensory neurons relative to support cells. These data identify a persistent epithelial inflammatory process associated with PASC, and suggests mechanisms through which this T cell-mediated inflammation alters the sense of smell.

neuroscience↗

bioRxiv2019

Discovering precise temporal patterns in large-scale neural recordings through robust and interpretable time warping

Though the temporal precision of neural computation has been studied intensively, a data-driven determination of this precision remains a fundamental challenge. Reproducible spike time patterns may be obscured on single trials by uncontrolled temporal variability in behavior and cognition, or may not even be time locked to measurable signatures in either behavior or local field potentials (LFP). To overcome these challenges, we describe a general-purpose time warping framework that reveals precise spike-time patterns in an unsupervised manner, even when spiking is decoupled from behavior or is temporally stretched across single trials. We demonstrate this method across diverse systems: cued reaching in nonhuman primates, motor sequence production in rats, and olfaction in mice. This approach flexibly uncovers diverse dynamical firing patterns, including pulsatile responses to behavioral events, LFP-aligned oscillatory spiking, and even unanticipated patterns, like 7 Hz oscillations in rat motor cortex that are not time-locked to measured behaviors or LFP.

neuroscience↗