INVOLVEMENT OF THE NUCLEUS ACCUMBENS TO VENTRAL PALLIDUM PATHWAY IN THE REGULATION OF SOCIAL PLAY BEHAVIOR IN JUVENILE MALE AND FEMALE RATS
Social play behavior is a highly rewarding behavior that is displayed in various mammalian species, including rats and humans. Engaging in social play is essential for the development of social skills necessary throughout life. Autistic children show decreased engagement in social play and fMRI studies implicate aberrations in the mesolimbic reward system that are associated with decreased social motivation and preference. The nucleus accumbens (NAc) and ventral pallidum (VP) are core brain regions of the mesolimbic reward system and individually regulate social play behavior in juvenile rats. Given that the NAc projects to the VP, I aimed to determine whether and how the NAc to VP pathway regulates social play behavior. NAc inputs to the VP are primarily GABAergic and studies show that inhibition of the NAc to VP pathway, which disinhibits the VP, promotes non-social rewarding behaviors, while stimulation of this pathway, which suppresses the VP, reduces non-social rewarding behaviors. Therefore, I hypothesized that inhibition of the NAc to VP pathway is required for the typical expression of social play behavior in juvenile male and female rats. In the first aim of my thesis (Chapter 2), I used Gad1-iCre juvenile rats, in which cre recombinase is expressed on Gad1 (glutamate decarboxylase 1, an enzyme required for GABA production) cells which allows for selective manipulation of the activity of GABAergic cells using cre-dependent DREADDs. I predicted that chemogenetic stimulation of the NAc to VP pathway would reduce social play behaviors in both sexes. I found that chemogenetic stimulation of NAc to VP pathway of Gad1-iCre juvenile rats reduced the duration of social play and other elements of social play such as the number of nape attacks, pins, and supine poses in both males and females. These effects were specific to social play, as Gad1-icre juvenile rats showed no changes in the duration of other social behaviors measured. Chemogenetic stimulation of NAcGABA terminals in the VP reduced the number of fos+, a marker of neuronal activation, VP cells, showing that activation of the NAc to VP pathway reduces VP activation. The second aim of my thesis (Chapter 3) determined whether social play exposure altered activation of VP-projecting cells in the two subregions of the NAc, the NAc core and shell, of juvenile male and female rats. I utilized the retrograde tracer cholera toxin subunit B (CtB) and fos in situ hybridization to quantify activated VP-projecting NAc cells. Although males and females showed a similar duration of social play, I found a sex-specific shift in activation of VP-projecting NAc cells following social play exposure. In both the NAc core and shell, there was a baseline sex difference in the activation of VP-projecting cells, such that males showed greater activation of VP-projecting cells compared to females. These baseline sex differences were eliminated by social play exposure in NAc subregion-specific ways. In the NAc core, social play exposure decreased the activation of VP-projecting cells in males. In the NAc shell, social play exposure tended to increase the activation of VP-projecting cells in females. Findings from Chapter 3 indicate that the equal expression of social play in males and females is associated with the elimination of a baseline sex difference in the activation of VP-projecting cells in the NAc core and shell in a sex-specific way. Overall, I provide the first evidence that inhibition of the NAc to VP pathway allows for the typical expression of social play behavior in juvenile male and female rats and this is associated with the elimination of a baseline sex difference in activation of the NAc to VP pathway.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- Attribution 4.0 International
- Material Type
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Theses
- Authors
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Lee, Jessica
- Thesis Advisors
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Veenema, Alexa H.
- Committee Members
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Lonstein, Joseph
Arguello, Amy
Mazei-Robison, Michelle
- Date
- 2023
- Subjects
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Social sciences
Psychophysiology
Neurosciences
- Program of Study
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Psychology - Doctor of Philosophy
- Degree Level
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Doctoral
- Language
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English
- Pages
- 159 pages
- Permalink
- https://doi.org/doi:10.25335/w7ss-yf44