Circuit-level developmental and functional dynamics in an autism genetic model

Anatomical and electrophysiological studies have made it clear that dysfunction in the cerebellum, and in Purkinje cells specifically, is linked to behavioral abnormalities in autism. This correlation is compelling, but it has been difficult to make a causative link between the anatomical and physiological defects and the associated behaviors.

Ethan Scott and his colleagues at the University of Queensland in Australia focus on the development and application of technologies for observing individual neurons, both in terms of their anatomical structure and their physiological activity. Scott and his group aim to use a combination of techniques to observe the development and function of Purkinje cells in a novel autism model: the zebrafish. They plan to generate mutants for genes implicated in autism in the zebrafish model system, and to then use sparse labeling of Purkinje cells to describe their anatomy in detail.

Because zebrafish larvae are transparent, the researchers also aim to take time-lapse images of Purkinje cell development in order to see what may be going wrong with the cells’ development or dynamics to generate previously described anatomical abnormalities.

Finally, Scott and his team plan to use optogenetics, a technique that uses beams of light to activate neurons in the brains of live animals, to observe the calcium dynamics in these developing neurons to learn whether the anatomical and developmental phenotypes have physiological consequences in developing and mature cerebellar circuits. Through these experiments, the researchers aim to gauge how cerebellar circuits become abnormal during development, and to provide leads for how the developmental impacts could be mitigated.