Search bioRxivSearch

bioRxiv · 10.1101/2020.05.04.076604

The effect of odor enrichment on olfactory acuity: Olfactometric testing in mice using two mirror-molecular pairs.

Abstract

Intelligent systems in nature like the mammalian nervous system benefit from adaptable inputs that can tailor response profiles to their environment that varies in time and space. Study of such plasticity, in all its manifestations, forms a pillar of classical and modern neuroscience. This study is concerned with a novel form of plasticity in the olfactory system referred to as induction. In this process, subjects unable to smell a particular odor, or unable to differentiate similar odors, gain these abilities through mere exposure to the odor(s) over time without the need for attention or feedback (reward or punishment). However, few studies of induction have rigorously documented changes in olfactory threshold for the odor(s) used for "enrichment." We trained 36 CD-1 mice in an operant-olfactometer (go/no go task) to discriminate a mixture of stereoisomers from a lone stereoisomer using two enantiomeric pairs: limonene and carvone. We also measured each subjects ability to detect one of the stereoisomers of each odor. In order to assess the effect of odor enrichment on enantiomer discrimination and detection, mice were exposed to both stereoisomers of limonene or carvone for 2 to 12 weeks. Enrichment was effected by adulterating the subjects food (passive enrichment) with one pair of enantiomers or by exposing them to the enantiomers in daily operant discrimination testing (active enrichment). We found that neither form of enrichment altered discrimination nor detection. And this result pertained using either within-subject or between-subject experimental designs. Unexpectedly, our threshold measurements were among the lowest ever recorded for any species, which we attributed to the relatively greater amount of practice (task replication) we allowed our mice compared to other reports. Interestingly, discrimination thresholds were no greater (limonene) or only modestly greater (carvone) from detection thresholds suggesting chiral-specific olfactory receptors determine thresholds for these compounds. The super-sensitivity of mice, shown in this study, to the limonene and carvone enantiomers, compared to the much lesser acuity of humans for these compounds, reported elsewhere, may resolve the mystery of why the former group with four-fold more olfactory receptors have tended, in previous studies, to have similar thresholds to the latter group. Finally, our results are consistent with the conclusion that supervised-perceptual learning i.e. that involving repeated feedback for correct and incorrect decisions, rather than induction, is the form of plasticity that allows animals to fully realize the capabilities of their olfactory system.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Coppola, D. M., Blount, A.. 2020-05-04. The effect of odor enrichment on olfactory acuity: Olfactometric testing in mice using two mirror-molecular pairs.. https://doi.org/10.1101/2020.05.04.076604

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

KEEP EXPLORING

Related preprints

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

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

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