Modulation of Olfactory Processing by Glucagon-like Peptide 1 Signaling

About This Grant

Project Summary Our sensory environment is rich with cues that influence behavior, particularly those related to food. Among these, olfactory cues are especially powerful, often initiating aspects of feeding behavior before the reception of visual stimuli. However, how these olfactory cues are processed and modulated by internal physiological states, such as satiety, remains poorly understood. I propose that the olfactory system integrates satiety signals to dynamically modulate odor processing and ultimately feeding behavior. This proposal focuses on glucagon-like peptide 1 (GLP-1), a satiety hormone produced in the hindbrain, which projects to olfactory structures including the piriform cortex (PCx). In aim 1 I will characterize the anatomical and functional connectivity between GLP-1-producing neurons in the nucleus of the solitary tract and the PCx. Furthermore, I will determine how GLP-1 signaling modulates excitatory and inhibitory drive onto PCx pyramidal neurons using patch clamp electrophysiology. In aim 2 I will use in vivo calcium imaging to determine how GLP-1 receptor activation modulates food related odor-driven behavior and olfactory representations in olfactory bulb and PCx output neurons. The fellowship training plan will provide me with advanced technical skills in systems neuroscience, including optical and electrophysiological recording, chemogenetic and optogenetic circuit manipulation, and behavioral analysis. Additional training will include computational approaches to sensory coding, professional development activities, grant writing, and structured mentorship. Research and training will take place in Dr. Joseph Zak’s lab at the University of Illinois Chicago, a collaborative and interdisciplinary environment with strong institutional neuroscience programs. This setting will equip the applicant to transition to an independent academic research career focused on the neural basis of motivated behavior and metabolic disorders. Together, these experiments will reveal the circuit and synaptic mechanisms through which internal state shapes olfactory processing, providing new insights into the neural basis of feeding behavior and potential targets for mitigating maladaptive eating.