ACHEMS 2025
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SPLTRAK Abstract Submission
Poster #118
Activity-Dependent Gene Regulation in Olfactory Sensory Neurons
Joshua Danoff & Kevin Monahan
Rutgers University, New Brunswick, NJ, United States

Olfactory sensory neurons (OSNs) adapt to odor environments by dampening their response to abundant odorants and heightening their response to rare odorants. Neuronal adaptation requires transcriptional changes that ultimately tune the activity of each OSN to its environment, but the gene regulatory mechanisms enabling these transcriptional changes are unknown. Using ATAC-seq and scRNA-seq, we investigate how gene regulation and transcriptional responses to new environments enable this adaptation. First, we find abundant differential chromatin accessibility among OSNs that are highly active compared to those that are not active. Activity-open peaks are enriched for known transcription factors in OSNs, including Lhx2 and Ebf, and the neuronal activity-dependent transcription factor Nfat. Gene ontology analysis indicates that activity-open peaks are associated with genes involved in synaptic transmission and olfactory perception. Using a paradigm where mice are exposed to new odor environments, we then examine the role of the chromatin organizer cohesin in rapid adaptation of OSNs to new environments. scRNA-seq of olfactory sensory neurons shows that cohesin (Rad21) knockout impacts the ability of OSNs to adapt to new environments in an olfactory receptor (Olfr) dependent manner. Some OSN subtypes, expressing a specific Olfr, are unable to adapt to new odor environments without cohesin expression, while other OSN subtypes are not impacted by cohesin knockout. These results demonstrate the involvement of chromatin organization in regulating activity-dependent transcriptional adaptations in OSNs. Further, they also identify molecular targets of olfactory neuronal activation by odors and have implications for understanding activity-dependent transcription in neurons generally.