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|Title:||A Potential Role for Adult-Generated Granule Cells in Social Memory|
|Abstract:||Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder that, among other symptoms, is associated with social memory deficits. ASD is heritable, and human genomic research implicates mutations and deletions of the Shank3 gene in ASD. Research links hippocampal structural plasticity with a variety of behaviors, including anxiety, spatial memory, and social memory. We investigated components of hippocampal plasticity in mice lacking the Shank3B gene. We first verified that Shank3B knockout (KO) mice have impaired social memory using a direct social interaction test. We further characterized hippocampal cognition and found that KO mice have normal object location memory. We then investigated plasticity in the CA2, a hippocampal subregion important for social memory. We examined perineuronal nets (PNNs), specialized extracellular matrix structures that regulate plasticity and enwrap some neurons, in the CA2 and found markers of PNNs and parvalbumin to be expressed normally in KO mice. We also investigated glia, which are implicated in synaptic function, in the CA2 and found normal microglia and astrocyte numbers in KO mice. We investigated another form of hippocampal plasticity, adult neurogenesis in the dentate gyrus (DG), as evidence suggests that adult-born neurons in the DG are important for social memory. We found that KO mice have fewer adult-born neurons in the superior blade of the DG. These findings correlated reduced hippocampal neurogenesis with impaired social memory. To investigate causality, we eliminated adult-born neurons in the DG using transgenic GFAP-TK mice and found that reducing adult-born neurons is sufficient to impair social memory. Together, we extend literature implicating adult-born neurons in social memory and expand upon research exploring neural contributors to symptoms seen in ASD.|
|Type of Material:||Princeton University Senior Theses|
|Appears in Collections:||Neuroscience, 2017-2020|
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