Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

Eye gaze and pupillary response in Angelman syndrome.

BackgroundAngelman syndrome (AS) is a rare neurological disorder characterized by severe developmental disability, communication impairment, elevated seizure risk, and motor system abnormalities.AimsThe aims of this study were to determine the feasibility of social scene eye tracking and pupillometry measures in individuals with AS and to compare the performance of AS participants to individuals with idiopathic Autism Spectrum Disorder (ASD) and typically developing controls (TDC).Methods and proceduresIndividuals with AS and age- and gender- matched controls completed a social eye tracking paradigm. Neurobehavioral characterization of AS participants was completed via a battery of psychological testing and caregiver behavioral evaluations.Outcomes and resultsEight of seventeen recruited AS participants completed the eye tracking paradigm. Compared to TDC, AS subjects demonstrated significantly less preference for social scenes than geometric shapes. Additionally, AS subjects showed less pupil dilation, compared to TDC, when viewing social scenes versus geometric shapes. There was no statistically significant difference found between AS and ASD subjects in either social eye tracking or pupillometry.Conclusions and implicationsThe use of eye tracking and pupillometry may represent an innovative measure for quantifying AS-associated impairments in social salience

Eye gaze and pupillary response in Angelman syndrome

BackgroundAngelman syndrome (AS) is a rare neurological disorder characterized by severe developmental disability, communication impairment, elevated seizure risk, and motor system abnormalities.AimsThe aims of this study were to determine the feasibility of social scene eye tracking and pupillometry measures in individuals with AS and to compare the performance of AS participants to individuals with idiopathic Autism Spectrum Disorder (ASD) and typically developing controls (TDC).Methods and proceduresIndividuals with AS and age- and gender- matched controls completed a social eye tracking paradigm. Neurobehavioral characterization of AS participants was completed via a battery of psychological testing and caregiver behavioral evaluations.Outcomes and resultsEight of seventeen recruited AS participants completed the eye tracking paradigm. Compared to TDC, AS subjects demonstrated significantly less preference for social scenes than geometric shapes. Additionally, AS subjects showed less pupil dilation, compared to TDC, when viewing social scenes versus geometric shapes. There was no statistically significant difference found between AS and ASD subjects in either social eye tracking or pupillometry.Conclusions and implicationsThe use of eye tracking and pupillometry may represent an innovative measure for quantifying AS-associated impairments in social salience