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Title: The Contribution of Cerebellar Circuitry to Sociocognitive Development: An Examination of Delay Eyeblink Conditioning in Purkinje Cell Tsc1 Deficient Mice
Authors: Cherskov, Adriana
Advisors: Wang, Sam
Department: Molecular Biology
Class Year: 2014
Abstract: Cerebellar dysfunction has recently been extensively implicated in the development of behavioral and cognitive abnormalities, which include deficits in working memory, emotional processing, and decision making. Compromised cerebellar function early in development has also been linked to autism spectrum disorders (ASDs) in humans and social deficits in mouse models. Understanding the role of the disruption of cerebellar neural circuits in the development of autism will therefore be a promising step in the pursuit of the etiology of the disorder. The experiments presented here establish the tools necessary to begin a thorough examination of the contribution of cerebellar circuits to the development of socio-cognitive deficits, such as those implicated in autism. In order to establish a possible learning behavioral paradigm that will allow us to test circuit rescue in future experiments, we examine the extent of deficits in cerebellar circuitry in the L7Cre;Tsc1 mutant model using delay eyeblink conditioning. Our finding of decreased cerebellar performance and learning indicate a possible deficit in synaptic and intrinsic plasticity in Purkinje cells. Furthermore, observed age-related effects suggest the extensive implication of compensatory mechanisms in cerebellar circuitry and the potential for increased impairment in Tsc1 cerebellar circuitry with age. This work also relates the establishment of the three-chambered social task that will be vital to future studies. These results also may indicate an improvement in social performance with age, and thus also establish this hypothesis for future exploration. Ultimately, we propose exciting avenue for future research as we explore the cerebellar circuitry of Tsc1 deficient animals.
Extent: 73 pages
Type of Material: Princeton University Senior Theses
Language: en_US
Appears in Collections:Molecular Biology, 1954-2020

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