Anatomical and Behavioral Characterization of NTS PPG Axonal Projections: PVH and VTA

Celine using microscope

Students

2019
College

Faculty

Professor Of Behavioral Neuroscience

Project Summary

Glucagon-like peptide 1 (GLP1) is produced in response to food consumption in the intestinal tract and by preproglucagon (PPG) neurons located in the nucleus of the solitary tract (NTS). Activation of the NTS PPG neurons is sufficient to trigger intake-inhibitory action in the CNS. A GLP-1 analog, liraglutide, has even been approved by the FDA to treat obesity. However, the anatomical organization of PPG axonal projections is still not completely known. As well, it is still unknown how endogenous GLP-1 satiation signaling contributes to the intake inhibitory effects in the CNS. Therefore, we started with an anatomical study using retrograde tracers in four feeding related areas of the brain and one non-feeding related area. Rats were injected with the tracers in two of these areas and all pairings were analyzed with immunohistochemistry. There were many areas showing dense projections from the NTS, such as the parabrachial nucleus. One pairing with a high level of co-localization was the paraventricular hypothalamus (PVH)*ventral tagmental area (VTA) pairing. With this preliminary data, we completed a behavioral experiment to test the relevance of these two areas in endogenous GLP-1 satiation signaling. In order to test this, we needed to create an endogenous signal by administering a preload in the form of an Ensure drink and then inject an antagonist (ex9) into one of the two areas of interest. Rats were assigned to one of four conditions: no preload + acsf, no preload + ex9, preload +acsf, preload + ex9. Each rat underwent all four conditions with a 48 hour recovery period between each. In the group that received injections into the PVH, there was an attenuation of the endogenous satiation signal at 30 minutes post injection. However, the VTA group did not show a significant attenuation effect. These results open the door to many more studies investigating the various roles of the PVH and VTA in regards to different aspects of the feeding system, such as motivation, satiation, aversion, etc. I’ve had the opportunity to work with many fascinating neuroscience technologies and practices, like brain harvesting and slicing, IHC, retrograde tracing, injections, data analysis and more. I certainly have learned a lot about the neurocircuitry of the feeding system, but learned how much is still unknown. I hope to pursue another independent study in the future to delve even deeper into this fascinating area of study.