Objectives: To further analyze the effect of Shank3 deficiency on neural pathways in brain regions related to ASD symptoms.
Methods: We developed a genetically modified rat model with a targeted disruption of Shank3, choosing a region of the gene relevant to human mutations. We are applying biochemical, electrophysiological, genome wide transcriptional analysis and behavioral studies to reveal changes due to Shank3-deficiency.
Results: We observe reduced levels of Homer and PSD-95 in the hippocampus and medial prefrontal cortex in Shank3-deficient rats. Our results also revealed that reduced levels of Shank3 lead to deficits in hippocampal long-term potentiation (LTP) and long-term depression. Furthermore LTP in the hippocampal-medial prefrontal pathway, analyzed using in vivo recordings of field excitatory responses, was also impaired in Shank3-deficient rats. Finally, Shank3-deficient rats showed a specific working memory deficit.
Conclusions: By further characterizing this rat model we will be able to reveal disrupted pathways that would then be targets for developing novel therapeutics for PMS and ASD.
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See more of: Biological Mechanisms