We are interested in the functions performed by the prefrontal cortex, a neocortical region involved in high-level cognitive processes such as executive function, working memory and regulation of emotional states. The prefrontal cortex forms diverse synaptic connections with many cortical and subcortical regions, and its function is impaired in psychiatric disease. Work in the lab will focus on the basic mechanisms of prefrontal function and on disease-related changes and their electrophysiological and behavioral correlates.
To investigate the physiology of neural circuits, my lab uses a technical approach called optognetics, that enables light-based control of neural activity in vitro and in vivo. Through the use of light-activated ion channels, pumps and receptors, optogenetics allows temporally and spatially precise control over the activity of defined circuit elements. By perturbing the physiology of a circuit, we can learn about its function and establish causal links between patterns of circuit activity and animal behavior.
In a recent publication, we designed and validated several novel optogenetic tools to study the effects of cortical excitation/inhibition balance on information processing and animal behavior. Using a stabilized step-function opsin (SSFO), developed by combinatorial mutagenesis of the channelrhodopsin gene, we could modulate excitation and inhibition in the mouse prefrotnal cortex and observed that an increase in the E/I balance leads to dramatic effects on cellular information processing, which correlated with impairment in innate and learned behaviors.
We used a chronic multisite optrode (CMO, see below) to record cortical activity under elevated E/I balance and found that this elevation leads to increased oscillcatory activity within the high-gamma range (60-90 Hz), a pattern reported at baseline in autism patients.
|
