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The role of corticotropin-releasing factor-expressing neurons in the anterior bed nucleus of the stria terminalis in effort-related motivation behaviors
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Maita, Isabella Vincenza. The role of corticotropin-releasing factor-expressing neurons in the anterior bed nucleus of the stria terminalis in effort-related motivation behaviors. Retrieved from https://doi.org/doi:10.7282/t3-bpvt-9n64

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TitleThe role of corticotropin-releasing factor-expressing neurons in the anterior bed nucleus of the stria terminalis in effort-related motivation behaviors
NameMaita, Isabella Vincenza (author); Samuels, Benjamin (chair); Pena, Catherine J (member); Roepke, Troy A (member); Margolis, David J (member); Rutgers University; School of Graduate Studies
Date Created2023
Other Date2023-05 (degree)
SubjectNeurosciences, Behavioral psychology, Psychobiology, Anxiety, Bed nucleus of the stria terminalis, Corticotropin releasing factor, Mood, Motivation, Stress
Extent170 pages : illustrations
DescriptionPsychiatric disorders including major depressive disorder, generalized anxiety disorder, and post-traumatic stress disorder are debilitating disorders often precipitated and exacerbated by stress. Current treatments for these stress-related psychiatric disorders are limited, so a recent shift toward personalized medicine has driven researchers to investigate specific symptoms of disorders and their neural substrates. Pre-clinical models of psychiatric disorder use avoidance and motivation behaviors to represent positive and negative valence symptoms that characterize human disorder. Here we investigate the involvement of two brain regions implicated in avoidance and motivation behaviors: the hippocampus and the bed nucleus of the stria terminalis (BNST). More specifically, we first used optogenetics to target a region of the hippocampus associated with both mood disorder and avoidance behaviors - the ventral dentate gyrus (vDG). We confirmed previous findings that optogenetic activation of the vDG reduces avoidance behaviors in the elevated plus maze. We then optogenetically targeted a projection from the principal output of the hippocampal formation, the ventral subiculum, to the dorsomedial nucleus of the BNST (dmBNST). Circuit tracing of vSUB-dmBNST projections did not produce reliable results. Next, we utilized a CRF-ires-Cre transgenic mouse line to target BNST cells expressing corticotropin-releasing factor (CRF), a molecule highly implicated in the stress response and avoidance behavior. Surprisingly, optogenetic activation of CRF-expressing (CRF+) anterior BNST (aBNST) cells did not reliably produce avoidance behaviors, but chemogenetic activation did increase avoidance in the open field. Unexpectedly, chemogenetic activation of CRF+ aBNST neurons reduced effortful motivation behavior. In a Y-maze effort-related choice task, mice were allowed to choose between a high effort/high reward arm, which required mice to climb a barrier for 4 palatable pellets, or a low effort/low reward arm with 2 pellets and no barrier. Chemogenetic activation of CRF+ aBNST neurons reduced selection of the high effort/high reward arm in both male and female mice. In an instrumental conditioning concurrent chow task, mice were allowed to choose between a high effort/high reward behavior of lever pressing at increasingly frequent rates for a more palatable food pellet, or a low effort/low reward behavior of consuming concurrently available, less preferred, lab chow. Chemogenetic activation of CRF+ aBNST neurons reduced lever pressing in male mice with high rates of baseline lever pressing. These experiments suggest a novel role for CRF+ aBNST neurons in incentive motivation and contribute to current knowledge on the neural circuitry of stress-related psychiatric disorder.
NotePh.D.
NoteIncludes bibliographical references
Genretheses
Persistent URLhttps://doi.org/doi:10.7282/t3-bpvt-9n64
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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