Increased Reliability of Visually-Evoked Activity in Area V1 of the MECP2-Duplication Mouse Model of Autism

Abstract

Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in layer 2/3 neurons of adult primary visual cortex in the MECP2-duplication syndrome animal model of autism. Increased response reliability was due in part to decreased response amplitude, decreased fluctuations in endogenous activity, and decreased neuronal coupling to endogenous activity. Similarly to what was observed neuronally, the optokinetic reflex occurred more reliably at low contrasts in mutant mice compared to controls. Retinal responses did not explain our observations. These data suggest that the circuit mechanisms for convolution of sensoryevoked and endogenous signal and noise may be altered in this form of syndromic autism.

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

“…2]. These effects occurred irrespective of genetic line background of the mice, as we used both 129-MECP2 duplication line and FVB*C57 mixed background duplication line (Ash et al, 2022). Reduced rate of perceptual reversals under visual rivalry conditions in MECP2 duplication mice recapitulates the phenotype occurring in human idiopathic autism.…”

“…In idiopathic human autism, hyperactivation of area V1 was found in a subset of subjects with autism during the processing of coherent motion (Brieber et al, 2010), while in another subset of subjects the areas of dorsal stream, including V1 and middle temporal area showed delayed activity during motion coherence processing (Robertson et al, 2014). Second, neuronal responses of MECP2 duplication mice in area V1 show reduced coupling to ongoing cortical activity (Ash et al, 2022). This may result in disruption of both feedforward inputs from V1 to higher order areas dedicated to integration of local moving cues into global motion percept and weakening of the feedback from these higher-order areas to V1, reducing the integration of local motion cues there (Ash et al, 2022).…”

“…Second, neuronal responses of MECP2 duplication mice in area V1 show reduced coupling to ongoing cortical activity (Ash et al, 2022). This may result in disruption of both feedforward inputs from V1 to higher order areas dedicated to integration of local moving cues into global motion percept and weakening of the feedback from these higher-order areas to V1, reducing the integration of local motion cues there (Ash et al, 2022). Taken together, these observations point to an interesting possibility that the over-representation of local component motion in area V1 and disrupted feedforward and feedback connections between V1 and the rest of the visual dorsal stream are major contributors to the reduced rate of visual rivalry in autism, as they confer advantage to the local motion information in the moving stimuli, while the synthesis of local information into the global motion of the scenes becomes impaired.…”

“…In our study, we applied a monocular rivalry paradigm to explore if the dynamics of bistable visual perception were affected in the mouse model of MECP2 duplication syndrome of autism (Collins et al, 2004). This model reproduces some features of human autistic syndromes, including enhanced motor learning, motor, and visual stereotypies, and increased likelihood of seizure events (Collins et al, 2004;Jiang et al, 2013;Samaco et al, 2012;Sztainberg et al, 2015;Zhang et al, 2017;Zhou et al, 2019;Ash et al, 2017Ash et al, , 2021bAsh et al, ,a, 2022. We found that the rate of perceptual reversals is decreased (Figure 2) in MECP2 duplication syndrome, while the average duration of individual percept dominance periods is prolonged (Figure 2).…”

“…In humans MECP2 duplication syndrome shows all core features of idiopathic autism (Ta et al, 2022; Peters et al, 2013). MECP2 duplication mice carry a number of core autism features including repetitive stereotyped behaviors, altered vocalizations, increased anxiety, motor savant phenotype and over-reliable visual responses (Collins et al, 2004; Samaco et al, 2012; Jiang et al, 2013; Sztainberg et al, 2015; Zhang et al, 2017; Zhou et al, 2019; Ash et al, 2017, 2021, 2022).…”