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Centrifugal regulation of olfactory function by melanin-concentrating hormone

US · IL NIH grant awarded #nih-5R01DC019379-05

Summary

This research project investigates how melanin-concentrating hormone (MCH) signaling and hypothalamic MCH neurons regulate olfactory function, particularly in response to physiological states like satiety and wakefulness.

What they want

The project aims to test the central hypothesis that centrifugal MCH neurons integrate physiological states and regulate olfactory function. Aim 1 will use molecular and biochemical techniques and mouse models to investigate changes in MCH levels in the olfactory bulb (OB) in response to food restriction and determine cellular targets of hypothalamic MCH neurons. Aim 2 will investigate MCH's effects on mitral cell activity in the OB, odor threshold detection, and cross-habituation, using animals lacking MCH signaling components and AAV-mediated MCHR1 removal in the OB. Aim 3 will investigate how disruption of primary cilia on OB neurons impacts odor detection and discrimination.
Deliverables
  • New mechanistic insight into the role of the lateral hypothalamus in regulating olfactory function
  • Understanding how changes in satiety or wakefulness impact the sense of smell
  • Insight into mechanisms of sensory dysfunction in ciliopathy patients
  • Establishment of future experiments to address molecular mechanisms of MCH modulation in the OB
Technical requirements
  • Molecular and biochemical techniques
  • Complementary mouse models
  • AAV mediated approaches
  • Investigation of primary cilia disruption
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