Altered sensory processing is a core and predictive feature of autism spectrum disorder (ASD)1. Current understanding of sensory processing comes largely from studies of the cerebral cortex. Behavior guided by sensory processing — sensory perception — depends on coordinated neural circuit activity spanning a hierarchy of multiple cortical areas; importantly, changes in neural circuits across multiple higher sensory areas are implicated in sensory alterations in ASD2. Although many studies link reduced activity in the primary sensory cortex to sensory alterations in ASD, there is a critical need to track sensory signals in neural circuits across multiple cortical areas during quantifiable impairments of sensory perception.
The goal of this proposal is to directly track cortical excitatory and inhibitory circuit activation across multiple higher visual areas during impaired visual perception in a mouse model of ASD (Cntnap2 knockout mice). Bilal Haider’s lab has established a novel approach that enables the study of cortical circuit activity during perceptual impairments. This approach was used in a previous study (supported by a SFARI Explorer Award) that quantified visual perceptual impairments in Cntnap2 knockout mice while simultaneously measuring activity in primary visual cortex (V1) excitatory neurons that communicate with higher cortical areas 3. The team now plans to perform optically targeted, multi-site recordings of neural population activity across multiple higher visual cortical areas during visual perceptual behavior.
This work will provide greater understanding of the circuits, cell types and activity patterns that lead to changes in sensory processing and perceptual behaviors relevant for ASD.
- Assessing sensory impairments and aberrant cortical circuit activity in Cntnap2 knockout mice
- Understanding and manipulating cortex-wide neural dynamics across multiple mouse models of autism
- Population coding in the sensory cortex in multiple mouse models of autism
- Identifying convergent cortical circuit impairments across multiple mouse models of autism