Center for Translational Neuroscience Distinguished Speaker Series Symposium on Drug Abuse

1. Center for Translational Neuroscience Distinguished Speaker Series Symposium on Drug Abuse Rayford Auditorium, Biomed II Bldg., 12 noon Tuesday, March 16, 2010 Optogenetic control of arousal and reward Luis De Lecea, PhD, Associate Professor Department of Psychiatry And Behavioral Science Stanford University

2. Our group identified and initially characterized the hypocretins (also known as orexins) about a decade ago. During this time, this peptidergic system has been demonstrated as a key modulator of arousal and beyond. We are now using targeted expression of two light activated channels, Channelrhodopsin and Halorhodopsin, to manipulate the activity of genetically defined subsets of neurons and establish causal relationships between their activity and behavior. Selective stimulation of hypocretin expressing neurons using ChR2 increases the probability of sleep-to-wake transitions. These transitions elicit activity in brain arousal centers such as the histaminergic TMN or noradrenergic LC enve with increased sleep pressure. Consistent with pharmacological data, chronic optogenetic photoinhibition of Hcrt neurons decreases wakefulness. Direct photostimulation of Hcrt neurons has also consequences on the activation of the HPA axis and in cocaine self-administration. Optogenetic stimulation of Hcrt postsynaptic targets, including noradrenergic and dopaminergic neurons has dramatic consequences on the states of arousal and hyperarousal associated with stress and addiction. Optogenetics has proved an effective tool to deconstruct the activity of brain arousal centers with unprecedented cellular specificity and millisecond temporal resolution.