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NIH grant 1F31DC023137-01A1: From scent to sustenance: Investigating the connection between the olfactory bulb and hypothalamic function
Institute: {'code': 'DC', 'abbreviation': 'NIDCD', 'name': 'National Institute on Deafness and Other Communication Disorders', 'admin_org_id': '12500019', 'admin_funding_url': ''}. PI: Martina Compagno. Award: $47613.
Start: 2026-08-08T00:00:00.
ABSTRACT
Increasing excitability of mitral and tufted cells in the olfactory bulb improves health and whole-body
metabolism. The impact of altered excitability in mitral and tufted cells on downstream targets of the olfactory
bulb and how this translates to enhanced metabolism remains unknown. The primary objective of my project
is to map functional connectivity between the olfactory bulb and the rest of the brain. My overall goal is to dissect
the connection between the olfactory bulb and neuroendocrine function. I hypothesize that enhanced
excitability in mitral and tufted cells can modify neuronal activation following food-related odor exposure
and restore activity in hypothalamic areas deleteriously affected by diet-induced obesity. The three
specific aims designed to investigate this hypothesis are: 1) To map odor-evoked immediate-early gene
activation and examine changes attributed to enhanced mitral and tufted cell excitability or diet-induced obesity.
2) To identify cell types, genes, and pathways upregulated in the paraventricular hypothalamus following odor
exposure. 3) To measure the effect of odor stimulation on neuroendocrine function. Enhanced activity in the
paraventricular hypothalamus protects against diet-induced obesity through altered neuroendocrine signaling. In
my studies, I will apply cell-selective CRISPR/Cas9 editing of the Kv1.3 ion channel to enhance mitral and tufted
cell excitability in these major output neurons of the olfactory bulb. My experiments are designed to modify diet
composition to induce obesity, followed by measurement of brain-wide changes in neural activation following
odor exposure visualized by tissue clearing and light sheet microscopy. Experiments examining the influence
of odor stimulation on neuroendocrine function will include—single-nuclear sequencing to identify cell types,
genes, and pathways altered in the paraventricular hypothalamus following odor exposure; RNAscope to validate
the genes identified; flurogold tracing to test whether odor-activated neurons are hypophysiotropic; and
assessing circulating hormone levels. Overall, my experiments will investigate the connection between the
olfactory bulb and hypothalamic function to uncover a potential mechanism of how enhanced olfactory function
may prevent diet-induced obesity. Obesity is a global health issue and feeding behavior is strongly influenced
by the sense of smell. Human studies indicate that individuals with obesity have reduced odorant detection and
modify consumption following exposure to energy-rich, appetitive food odors. For this reason, it is critical to
investigate the functional connection between olfaction and metabolism, particularly in obese states.document fetched 2026-08-16 06:34