Event:

Atypical sensory processing in neurodevelopmental disorders contributes to cognitive, social, and behavioural disruptions and often predicts these impairments. However, underlying neurophysiological mechanisms remain unclear. Using a mouse model of SYNGAP1 haploinsufficiency (HET), a common monogenic cause of intellectual disability and autism spectrum disorders, we investigated visual processing deficits. Neurons in the primary visual cortex (V1) of Syngap HET mice exhibited reduced response reliability and coding precision for visual stimuli. These cortical deficits were associated with reduced behavioural visual discriminability. Notably, intrinsic properties of V1 neurons and visual responses under anaesthesia were unaltered. Larger pupil diameter during visual stimulation in Syngap HET mice suggested disrupted behavioural state modulation. Consistent with this observation, systemic administration of guanfacine, an alpha-2-adrenoreceptor agonist, restored V1 coding precision in Syngap HET mice. Our findings reveal neuromodulatory dysregulation as a novel mechanism underlying sensory disruptions in SYNGAP1-related disorder, highlighting potential therapeutic targets for addressing sensory impairments in neurodevelopmental disorders.