Date of Award

2024-05-01

Degree Name

Master of Science

Department

Biological Sciences

Advisor(s)

Arshad M. Khan

Abstract

Within the last decade, the number of diseases associated with dysregulation of the neural circuits responsible for energy balance, glucosensing, and feeding control has increased. One brain region containing these circuits is the lateral hypothalamic area (LHA), which plays an important role in the sleep/wake cycle, energy balance, and motivated behavior. Although the LHA has been termed a â??feeding centerâ??, other regions within the hindbrain are known for the regulation of similar functions including energy balance, glucosensing, and feeding control. While many studies have explored and reported projections from the LHA to the hindbrain, few have further investigated the interconnections between neighboring cytoarchitectonically defined LHA subdivisions. To address this gap in our understanding, we have surveyed three distinct regions within the LHA, as characterized in the standardized atlas, Brain Maps 4.0 (BM4.0). We injected a cocktail consisting of the retrograde tracer, cholera toxin subunit B (CTb), and the anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L), in three adult male Sprague-Dawley rats to visualize their LHA interconnections with the hindbrain. We mapped the traced interconnections to hindbrain atlas levels 52â??73. Of the three cases, subject 19-054 displayed unique connectional patterns for various HB subregions. Through various IHC preparations, we observed sources of LHAd inputs in the form of CTb-ir perikarya, and LHAd outputs in the form of PHA-L-ir axons in reticular nuclei and regions within the dorsal vagal complex (DVC). Hence, bidirectional communication, as evident from both retrograde and anterograde labeling, exists for the proposed LHAdâ??HB neural circuits. We also phenotyped some of the neuronal populations in the hindbrain overlapping with these regions. Overall, this provides evidence for the existence of bidirectional structural connectivity for the LHAdâ??DVC neural circuit, and provides a foundation for its further elucidation. Obtaining accurate standardized maps in addition to molecular information of this neural circuit in relation to the regulation of gastrointestinal function and feeding behavior will be critical for generating effective therapies. The further delineation of this neural circuit may also prove critical for the development of novel therapeutic strategies aimed for the treatment of diabetic patients. Furthermore, by confirming LHAd connections to the hindbrain DVC, we can create and test hypotheses about how these connections work, supplemented by standardized maps of the entire network that may be utilized for large-scale projects such as deep brain stimulation, optogenetics, and even the use of light-sheet microscopy to produce a 3-D map of this important neural circuit.

Language

en

Provenance

Received from ProQuest

File Size

106 p.

File Format

application/pdf

Rights Holder

Jessica Valeria Salcido Padilla

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