bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2021.04.19.440489

Redundant neural circuits regulate olfactory masking

Yang, W.·Wu, T.·Tu, S.·Choi, M.-K.·Duan, F.·Zhang, Y.
View original source ↗Export metadata ↓

Abstract

Olfactory masking is a complex olfactory response found in humans. However, the mechanisms whereby the presence of one odorant masks the sensory and behavioral responses elicited by another odorant are poorly understood. Here, we report that Caenorhabditis elegans displays olfactory masking and that the presence of a repulsive odorant, 2-nonanone, that signals threat strongly masks the attraction of other odorants, such as isoamyl alcohol (IAA) or benzaldehyde that signals food. Using a forward genetic screen, we found that several genes, osm-5, osm-1, and dyf-7, known to regulate the structure and function of sensory neurons played a critical role in olfactory masking. Loss of these genes mildly reduces the response to 2-nonanone and disrupts the masking effect of 2-nonanone. Restoring the function of OSM-5 in either AWB or ASH, two sensory neurons known to mediate 2-nonanone-evoked avoidance, is sufficient to rescue olfactory masking. AWB is activated by the removal of 2-nonanone stimulation or the onset of IAA; however, the mixture of 2-nonanone and IAA stimulates AWB similarly as 2-nonanone alone, masking the cellular effect of IAA. The latency of the AWB response is critical for the masking effect. Thus, our results identify redundant neural circuits that regulate the robust masking effect of a repulsive odorant and uncover the neuronal and cellular basis for this complex olfactory task. AUTHOR SUMMARYIn their natural environment, animals, including humans, encounter complex olfactory stimuli. However, regardless how complex the stimuli are, the behavioral output can only be one. Thus, how the brain processes multiple sensory cues to generate a coherent behavioral output is critical for the survival of the animal. In the present study, we combined molecular cellular genetics, optical physiology and behavioral analysis to study olfactory masking, a common olfactory phenomenon in which the presence of one odorant masks the stimulation of another odorant. Our results show that olfactory masking is regulated by redundant neuronal circuits, a mechanism that likely ensures the robust behavioral response to the sensory cue representing information critical for the survival.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Yang, W., Wu, T., Tu, S., Choi, M.-K., Duan, F., Zhang, Y.. 2021-04-20. Redundant neural circuits regulate olfactory masking. https://doi.org/10.1101/2021.04.19.440489

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↗