Advisor(s)
Lucas Pozzo-Miller
Committee Member(s)
Andrew Hardaway
Jeremy Day
Juan Belforte
Karen Gamble
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Neurobiology
Date of Award
1-6-2025
Abstract
Social behaviors are critical for the survival of individuals, and their dysfunction is common in several neuropsychiatric and neurodevelopmental disorders including autism, where impaired sociability is one of the core diagnostic symptoms and compromises the interpretation of social cues, with an apparent lack of interest in others. Among the neurodevel opmental disorders associated with autism, Rett syndrome (RTT) is a disorder predominantly affecting females and caused by spontaneous loss-of-function mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator MeCP2 that regulates many critical genes. RTT individuals have impaired motor, cognitive, and social abilities most of which are recapitulated in mouse models based on Mecp2. We initially ruled out alterations in odor discrimination as a factor contributing to the social memory deficits observed in previous results using Mecp2 KO mice. Subsequently, we examined social engagement and the stability of social hierarchy among male mice, processes that rely on intact social memory. Our findings reveal that wild-type (WT) mice rapidly establish a stable, active, and robust social hierarchy post-social competition, whereas Mecp2 KO mice exhibit a passive social hierarchy with reduced social interactions and competitive behaviors. We further confirmed the presence and responsiveness of social-sensitive neurons within the mPFC during social interactions in both WT and Mecp2 KO mice. We then utilized chronic manipulations of vHIP-mPFC projection neurons to determine whether disrupted vHIP activity could influence social hierarchy formation in WT mice, and whether reducing aberrant vHIP activity in Mecp2 KO mice could enhance social engagement and alter social hierarchy profiles. Our results indicate that chronic modulation of vHIP activity effectively alters social hierarchy profiles in both genotypes. Finally, we investigated the role of BDNF by modulating the transcription of Bdnf exon-I in the vHIP, assessing its impact on social hierarchy formation in WT and Mecp2 KO mice. However, BDNF manipulation alone was insufficient to modify social hierarchy profiles. Collectively, these findings provide insight into the role of the vHIP-mPFC pathway in the formation and maintenance of social hierarchies in both WT and Mecp2 KO mice
ProQuest ID
Recommended Citation
Acevedo Triana, Cesar Andres, "Social Dominance And Cortical Neuronal Synchrony In Male Mecp2 Knockout Mice" (2025). All ETDs from UAB. 7297.
https://digitalcommons.library.uab.edu/etd-collection/7297
