Date of Completion
Honors College Thesis
Honors College, College of Arts and Science Honors
mTOR, ASD, PTEN, Spatial Accuracy, Neophobia, Raptor
The Pten gene is a critical part of the mTOR pathway, encoding for cell growth. Mutation of the Pten gene in children results in enlargement of the head, epilepsy, and cognitive deficits on the Autistic Spectrum. The animal model was created to selectively knockout (KO) the gene in hippocampal granule cells and to observe their developmental growth characteristics and integration into the entorhinal cortex-hippocampal pathway. A recent study showed that this animal model also exhibited difficulties in reconciling new information and associating a familiar goal cue with novel spatial locations. We studied a genetic rescue of this phenotype through double KO (DKO) of Pten and Raptor genes in the mTOR pathway, which has been shown to rescue neuronal hypertrophy associated with Pten KO. We hypothesized that correction of Pten KO associated dendritic overgrowth in dentate gyrus granule cells will also rescue spatial cognitive deficits. However, Pten/Raptor DKO mice exhibited significantly worse performance than controls on the spatial accuracy task, most notably during the hidden cue session. One likely reason for this poorer performance is that DKO mice showed thigmotaxic behavior in the open arena in response to elimination of olfactory cues and removal of the hidden cue, suggesting neophobia. As morphological rescue was not found to rescue cognitive deficits, this strongly suggests that non-canonical mechanisms of mTOR may significantly affect entorhinal-hippocampal network activity and emotional responses to spatial novelty in the DKO model.
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Pressman, Rachel D., "Spatial Accuracy in Pten/Raptor Double Knockout Mice: Implications for the Underlying Cause and Treatment of Cognitive Impairments in an Animal Model of Autism Spectrum Disorder" (2023). UVM Honors College Senior Theses. 585.
Available for download on Sunday, May 04, 2025