Dissertation
The VLM A1/C1 CA/NPY Neuronal Projections to the Perifornical Area of the Lateral Hypothalamus and Its Functional Role in Glucoprivic Feeding
Washington State University
Doctor of Philosophy (PhD), Washington State University
2023
DOI:
https://doi.org/10.7273/000005278
Abstract
During acute glucose deficit (glucoprivation), the brain mediates several counter-regulatory responses (CRRs) to facilitate restoration of euglycemia. Such responses include increased food intake, corticosterone secretion, epinephrine release, and blood glucose level. However, repeated incidents of hypoglycemia, especially in diabetic patients, can cause development of Hypoglycemia Associated Autonomic Failure (HAAF), in which one’s brain loses its ability to detect blood glucose level, and thus fails to generate CRRs. HAAF can result in sustained hypoglycemia, leading to seizures, irreversible brain damage, or death. Hence, it is imperative that we better understand the neural circuitry of CRR activation during glucoprivation. Prior work from our lab established that glucoprivic feeding requires ventrolateral medullary (VLM) catecholamine (CA) neurons that co-express neuropeptide Y (NPY). However, the connections by which VLM CA/NPY neurons trigger increased feeding are uncertain. Past work in our lab demonstrated that VLM A1/C1 CA neurons activate perifornical lateral hypothalamic (PeFLH) neurons during glucoprivation. We therefore hypothesized that NPY co-expressed by the VLM CA neurons activates the PeFLH neurons to elicit the glucoprivic feeding response. To investigate the functional role of the NPY signaling pathway from the VLM to the PeFLH during glucoprivic feeding, we utilized the ribosomal toxin conjugate, NPY-saporin (NPY-SAP) to selectively lesion NPY receptor-expressing neurons in the PeFLH of male and female rats. We then evaluated the effect of these selective immunotoxic lesions on glucoprivic feeding evoked by 2-Deoxy-D-glucose (2DG), an anti-metabolic glucose analogue that inhibits glycolysis. To determine the subtypes of NPY receptors involved in the VLM-to-PeFLH signaling, we pharmacologically blocked NPY receptors in the PeFLH during chemogenetic activation of VLM A1/C1 CA neurons in transgenic TH-Cre+ rats. We found that NPY-SAP lesioned significant numbers of PeFLH neurons including a subpopulation of orexin, but not melanin-concentrating hormone neurons. The PeFLH NPY-SAP lesions attenuated 2DG-evoked feeding but did not affect 2DG-evoked increase in locomotor activity, corticosterone secretion, or sympathoadrenal hyperglycemia. Finally, antagonism of PeFLH NPY receptors attenuated feeding evoked by chemogenetic activation of VLM CA neurons in male and female rats. Also, in male rats, antagonism of PeFLH NPY receptors attenuated feeding evoked by 2DG. We conclude that a VLM CA neuron projection to the PeFLH is necessary for glucoprivic feeding, and that feeding evoked by activation of this pathway is mediated by NPY.
Metrics
7 File views/ downloads
61 Record Views
Details
- Title
- The VLM A1/C1 CA/NPY Neuronal Projections to the Perifornical Area of the Lateral Hypothalamus and Its Functional Role in Glucoprivic Feeding
- Creators
- Pique Choi
- Contributors
- Suzanne M Appleyard (Advisor)Robert C Ritter (Committee Member)Heiko Jansen (Committee Member)Ilia Karatsoreos (Committee Member)James H Peters (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Program in Neuroscience
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 155
- Identifiers
- 99901019636801842
- Language
- English
- Resource Type
- Dissertation