Transcript Document

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
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.