Authors:

Violet Saldarriaga

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About Paper:

Autism Spectrum Disorders (ASDs) are characterized by deficits in learning, social behavior, and sensory integration. Fragile X syndrome (FXS), caused by a mutation in the FMR1 gene, is a prominent genetic cause of ASD. Recent research has revealed impaired functioning of parvalbumin (PV) interneurons (INs) in ASD. These INs play a crucial role in regulating inhibitory and excitatory processes in cortical pyramidal neurons, which subsequently impacts behavior, learning, and memory. Learning deficits in Fragile X Knockout (FX) mice compared to wild-type (WT) mice have been studied; however, the role that PV INs play in visual learning processes is still unknown. Here, we investigated whether rescuing FMR1 protein (FMRP) function in PV interneurons can restore the learning impairments observed in FX mice. Using a novel conditional knock-in mouse strain, Fmr1 cON/PV-Cre (CON), we specifically restored FMRP in PV interneurons only. To measure behavior, freely moving mice were placed in touchscreen chambers and learned a visual discrimination go/no- go task. By incorporating a delay between the offset of the stimulus and when the mice perform the task, we could specifically focus on measuring behavior during a delayed working memory period. We assess the performance of FX and CON mice, with WT mice serving as control, by quantifying training scores (Hits and Correct Response Values minus the normalized False Alarms and Misses) across days of training. We found that there is a significant difference in the response time between WT and FX. CON response time is significantly better than FX and equivalent to WT. Furthermore, CON training scores are an intermediate between FX and WT. Results show that restoring FMRP function in PV INs improves performance in visual learning tasks compared to FX. This evidence suggests that PV interneurons play a critical role in visual processing and memory and could underly the learning disability present in ASD. The results of this project provide more insights into the learning and memory deficits exhibited by FX mice while also working to precisely examine the role of PV INs in network responses to stimuli. The findings work to unveil notable behavioral differences across the three mouse strains and suggest new potential therapies for treating symptoms of ASD.

Source:

Purdue University / 2023

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Co-authors:

Violet Saldarriaga