LAUSR

GLP1-immunopositive axons are present within a large number of subcortical brain regions in rats and mice. GLP1 neurons are activated/recruited by stress-related stimuli, and central GLP1 receptor signaling contributes to a variety of behavioral and physiological stress responses. GLP1-positive axons originate from a small cluster of glutamatergic GLP1 neurons, whose cell bodies occupy the hindbrain caudal nucleus of the solitary tract (cNTS) and intermediate reticular nucleus (IRt). The present study sought to determine whether GLP1 axonal inputs to distinct brain regions arise from distinct subsets of these hindbrain neurons. We recently developed and characterized a new knock-in Sprague Dawley rat model (Gcg-Cre) in which GLP1 neurons within the cNTS and IRt express iCre (DOI: 10.1016/j.molmet.2022.101631 ). Using this rat model, specific hypothalamic and limbic forebrain nuclei that receive GLP1 input were stereotaxically microinjected with Cre-dependent retrograde AAVs (i.e., AAVrg-EF1a-DIO-hChR2:mCherry and AAVrg-EF1a-DIO-hChR2:EYFP). These AAVs fully label the cell bodies, dendrites, and axon collaterals of Cre-expressing neurons that project to each injection site. AAVrg injections into the paraventricular nucleus of the hypothalamus (PVN) labeled GLP1-positive neurons within the cNTS and IRt. Interestingly, labeled axon collaterals of PVN-projecting GLP1 neurons were present within not only the PVN, but in every brain region previously described as containing GLP1-positive axons. Similar results were obtained after AAVrg was injected into the bed nucleus of the stria terminalis. While labeling generated from other AAVrg injection sites remains to be examined, results thus far suggest that individual GLP1 neurons have widely branching axons that target multiple CNS regions. The data suggest that GLP1 neurons broadcast signals simultaneously to multiple subcortical targets, consistent with GLP1 receptor-mediated modulation of overall behavioral state, rather than elicitation of specific behaviors or physiological processes. NIH grant MH059911 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.