Autism spectrum disorder (ASD) is classically characterized by its social and cognitive symptoms, but changes in sensory processing also occur, and these may contribute to, or even be causative in, the core features of ASD. At the circuit and network levels, sensory processing remains relatively mysterious, largely due to the challenges of monitoring activity across whole populations of neurons in intact, functioning brains.
With the goal of better understanding sensory processing networks and the ways that they may be affected in ASD, Ethan Scott and his colleagues plan to perform whole-brain calcium imaging in larval zebrafish. These larvae are optically transparent, which permits the monitoring of genetically-encoded calcium indicators across the brain at cellular resolution.
This project uses approaches developed in the Scott lab over the past several years and which were funded, in part, by previous SFARI (Explorer and Pilot) awards. Scott and his team plan to detect activity from tens of thousands of neurons simultaneously while the animals respond to an array of visual1, auditory2 and vestibular stimuli3. Along with follow-up anatomical and histochemical analyses, this is intended to reveal the response profiles, locations, morphologies and neurotransmitter use of sensory-responsive neurons throughout the brain.
Such studies will enable Scott’s team to model the flow of information through the brain’s circuits and networks as the animal perceives stimuli. The researchers will study these networks not only during the stimulation of individual senses but also during sensory integration across multiple senses and during simple forms of sensory learning, which are often altered in ASD. With these baseline descriptions of sensory processing, integration and learning in place, they will proceed to study the same circuits and networks in larvae with mutations in ASD risk genes (e.g., fmr1-/-, scn1lab, and mecp2 mutants).
The goal of these studies is to describe the specific changes in neurons, regional circuits and brain-wide networks that underlie sensory phenotypes in these mutants, thereby providing leads for understanding the same phenomena in individuals with ASD.