Assessing sensory impairments and aberrant cortical circuit activity in Cntnap2 knockout mice
- Awarded: 2018
- Award Type: Explorer
- Award #: 600343
The cerebral cortex is the dominant structure of the mammalian brain, and it is widely affected in autism spectrum disorders (ASD), with impairments in sensory processing reflecting a core and predictive feature of ASD. However, our understanding of cortical sensory processing arises largely from studies in simplified conditions, such as in brain slices or during anesthesia. These approaches have provided fundamental knowledge but are limited in their ability to measure cortical circuit dysfunctions moment by moment during impairments of perception.
Bilal Haider’s laboratory has established a novel approach spanning multiple scales that addresses these challenges for understanding sensory impairments in ASD. Haider previously pioneered methods to record excitatory and inhibitory synaptic activity in the cortex of awake mice1, 2. Haider’s laboratory now proposes to merge this framework with simultaneous multisite large-scale recordings of population activity across layers of primary visual cortex (V1) in a genetically relevant ASD mouse model (Cntnap2-/-) during active detection of visual stimuli for rewards.
The goals of this proposal are to 1) rigorously quantify impairments of sensory perception in ASD mice, 2) define how local field potentials (LFPs) across cortical layers predict impaired visual perception, and 3) define how excitatory and inhibitory neuron populations spanning cortical layers predict impaired visual perception in ASD mice. By investigating sensory cortex during perception across multiple levels, Haider expects to build a detailed picture of how cortical circuit dysfunctions in ASD mouse models lead to misperception of the external sensory world.