Visual, perceptual and neurophysiological alterations in an Scn2a knockout rat model of autism

  • Awarded: 2022
  • Award Type: Targeted: Autism Rat Models Consortium
  • Award #: 986751

Atypical sensory experiences affect around 90 percent of individuals with autism spectrum disorder (ASD). In the visual modality, these anomalies include a propensity to process local rather than global features of visual patterns, an inability to deploy configural processing strategies (resulting in, for example, difficulties in face discrimination) and challenges in extracting structural regularities in the sensory environment (resulting in, for example, difficulties in extracting perceptual invariants).

Understanding the neuronal underpinnings of these anomalies is challenging because of the limited tools that are available to record and manipulate neuronal activity in humans. Although many mouse genetic models of ASD exist, mouse visual perception is still poorly understood in terms of high-order visual processing (e.g., object recognition). By contrast, advanced visual processing abilities have been demonstrated in rats, both at the perceptual1 and cortical level2,3. The development of SFARI rat genetic models of ASD now affords the unique opportunity of studying whether anomalies in visual perceptual and functional cortical processing co-occur with circuit-level differences and whether the latter are causally implied in the former.

A pilot study pursuing this research line will be carried out by Davide Zoccolan and his colleagues at the Scuola Internazionale Superiore di Studi Avanzati (SISSA) of Trieste (Italy). Zoccolan and his team will focus on a rat model of autism in which Scn2a, a high-confidence ASD risk gene, has been knocked-out. The investigators will compare visual perceptual abilities of mutant and wildtype rats in a battery of visual discrimination tasks aimed at specifically assessing those processes (such as invariant recognition and configural processing) that are often affected in people with ASD. At the same time, they will investigate the neuronal correlates of these processes by performing large-scale neuronal recordings from multiple visual cortical areas of mutant and wildtype rats. These experiments will test whether the tuning of visual cortical neurons is altered in a way that is consistent with the perceptual behavior assessed through psychophysics.

Overall, these experiments will test the hypothesis that some key cortical computations that are critical for sensory processing are altered in ASD. Outcomes from these studies are expected to pave the way for future circuit-level dissections of the underlying anatomical substrates and, possibly, to restorative strategies through reactivation of potentially affected circuit components (e.g., using opto- and chemo-genetic approaches).


  1. Djurdjevic, V. et al. Curr. Biol. 28, 1005-1015 (2018) PubMed
  2. Tafazoli, S. et al. eLife 6, e22794 (2017) PubMed
  3. Piasini, E. et al. Nat. Commun. 12, 4448 (2021) PubMed
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