Cognitive and behavioral impairments in autism spectrum disorders are thought to result from changes in the structure and function of brain circuits. Disruption of the balance between excitation and inhibition in the neocortex has been proposed as a possible mechanism. This type of imbalance could lead to altered neuronal network connections that give rise to dramatic changes in the way the brain processes information and regulates behavior.

Ofer Yizhar and Elad Schneidman of the Weizmann Institute in Israel plan to examine the relationship between altered excitation/inhibition (E/I) balance and circuit connectivity in the brain. First, the researchers plan to record the activity of large ensembles of cortical neurons in mice that have been chronically exposed to altered E/I balance states, using optogenetic and pharmacogenetic manipulations. This would allow them to examine, at the millisecond timescale, the changes in cortical circuit dynamics that result from such chronic alterations.

Then, using electrophysiological recordings, calcium imaging and optogenetic manipulation, they aim to construct high-resolution maps of cortical connectivity in mouse models of autism. This would allow the researchers to examine how functional connectivity in these networks shapes their spontaneous and stimulus-evoked activity. Finally, computational analysis of the functional organization of the networks would provide a comprehensive description of cortical network function under altered E/I balance states.