Tug-of-peace: Visual Rivalry and Atypical Visual Motion Processing in MECP2 duplication Syndrome of Autism.

Extracting common patterns of neural circuit computations in the autism spectrum and confirming them as a cause of specific core traits of autism is the first step towards identifying cell- and circuit-level targets for effective clinical intervention. Studies in humans with autism have identified functional links and common anatomical substrates between core restricted behavioral repertoire, cognitive rigidity, and over-stability of visual percepts during visual rivalry. To study these processes with single-cell precision and comprehensive neuronal population coverage, we developed the visual bi-stable perception paradigm for mice based on ambiguous moving plaid patterns consisting of two transparent gratings drifting at an angle of 120°. This results in spontaneous reversals of the perception between local component motion (plaid perceived as two separate moving grating components) and integrated global pattern motion (plaid perceived as a fused moving texture). This robust paradigm doesn't depend on the explicit report of the mouse, since the direction of the optokinetic nystagmus (OKN) is used to infer the dominant percept. Using this paradigm, we found that the rate of perceptual reversals between global and local motion interpretations is reduced in the methyl-CpG binding protein 2 duplication syndrome (MECP2-ds) mouse model of autism. Moreover, the stability of local motion percepts is greatly increased in MECP2-ds mice at the expense of global motion percepts. Thus, our model reproduces a subclass of the core features in human autism (reduced rate of visual rivalry and atypical perception of visual motion). This further offers a well-controlled approach for dissecting neuronal circuits underlying these core features. Significance Statement Autism is a disorder of distributed computations, spanning low-level sensation and high-level sensorimotor integration, decision-making and social cognition. A distributed computation involving both low-level sensory and high-level executive processes, visual rivalry represents a potential candidate approach for the study of autism. We developed and applied the monocular rivalry paradigm based on competition between local and global visual motion in the mouse model of monogenic autism - MECP2 duplication syndrome. MECP2 duplication mice show slowed visual rivalry and favor local over global motion interpretation of the stimulus. This recapitulates the phenotype of human idiopathic autism and offers a way to dissect the circuit of altered visual motion processing and visual rivalry in autism using mouse models of autism.