Noradrenergic-dependent visual disruption and restoration in a SYNGAP1 Mouse Model of Intellectual Disability and Autism
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Date:
Feb 25, 2025
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Time:
11:00 AM - 12:00 PM (Local Time Germany)
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Speaker:
Nathalie Rochefort
- University of Edinburgh, Centre for Discovery Brain Sciences, Edinburgh
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Location:
MPI BI Martinsried
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Room:
MPIBI, Seminar room NQ 105
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Host:
Mark Hübener
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Contact:
mark.huebener@bi.mpg.de
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 α2-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.