34th Annual W. Alden Spencer Award and Lecture
Date: November 28, 2011 from 5:00 pm to 6:30 pm EST
Location: P&S Alumni Auditorium.
Contact: For further information regarding this event, please contact Clayton Eccard by sending email to che2107@columbia.edu or by calling 212-543-5202.
 

Karl Deisseroth is recognized for the development and application of optogenetics: the integration of genetics and optics to achieve gain- or loss-of-function of well-defined events (such as action potential patterns) in defined cell types within intact biological systems. This optogenetic control is achieved with high fidelity using microbial opsin genes, taken from evolutionarily distant organisms such as algae and archaebacteria that encode single component light-activated regulators of transmembrane ion conductance.

 

Since Deisseroth’s transduction of microbial opsins into neurons in 2004, while supported as principal investigator by the National Institute of Mental Health and Stanford University, publications from his team beginning in 2005 have demonstrated a number of remarkable and surprising properties for this optical control of neural activity: single-componency (functional control of vertebrate neurons with just an opsin gene, in the absence of added cofactors), safety and tolerability, millisecond-scale control of spiking, and reliability in delivering sustained and defined spike trains. To help enable reliable in vivo application, Deisseroth and his colleagues have generated 1) faster and more potent opsins for fidelity at high spike rates and low light levels; 2) bistable (step-function) opsin mutants that allow cells to be switched into and out of stable excitable states with single flashes of light; 3) redshifted opsins for combinatorial control with blue light-activated opsins; 4) generalizable methods for targeting opsins; and 5) the fiberoptic/laser diode device to allow optogenetic control of any brain region or tissue in freely-moving mammals. In 2007 Deisseroth and his colleagues applied this fiberoptic/laser diode device to selectively drive hypocretin/orexin neurons in behaving mice. Activity parameters were systematically mapped that were sufficient to drive awakening, thereby establishing for the first time a causal relationship between specific spiking patterns of a genetically defined neural cell type and a specific complex behavior.

 

Deisseroth has also led disease-focused work, initially in 2009 by optogenetically targeting the subthalamic nucleus to determine controversial circuit mechanisms of deep brain stimulation (DBS) relevant to Parkinson's disease and depression, and revealing the important result that the initial direct target of DBS is afferent axons within the target structure. Deisseroth’s team also used optogenetics to support a causal role for cortical parvalbumin neurons in specific kinds of brain rhythmicity (gamma oscillations) relevant to schizophrenia and autism, and to implicate these gamma waves in modulating the flow of information. In 2010 and 2011, Deisseroth’s teams identified a casual role for accumbens cholinergic neurons in cocaine conditioning, and mapped out a specific amygdala projection causally involved in anxiety. Most recently, Deisseroth’s team found that profound social behavior dysfunction can be elicited by temporally-precise elevation of excitation/inhibition balance in prefrontal cortex of freely-moving mice-- without nonspecifically altering anxiety or novel-object exploration, but instead eliciting key clinical signs including elevated baseline high-frequency (gamma) EEG power in neocortex.

 

In 2010 the Nature journals named optogenetics Method-of-the-Year, and Science headlined the “Insights of the Decade” with Deisseroth’s work.  Among other awards, for developing and applying optogenetics, Deisseroth has received the NIH Director’s Pioneer Award and the McKnight Foundation Technological Innovations Award, and was the sole recipient of the 2010 Koetser Prize and the 2010 Nakasone Prize. In 2010 he was elected to the Institute of Medicine.

 

A native of Boston, Deisseroth received his bachelor's degree from Harvard in 1992, his Ph.D. from Stanford in 1998, and his M.D. from Stanford in 2000. He completed postdoctoral training, medical internship, and adult psychiatry residency at Stanford, and he was board-certified by the American Board of Psychiatry and Neurology. He is a faculty member in the Bioengineering and Psychiatry Departments at Stanford, and continues as a practicing inpatient and outpatient psychiatrist at Stanford, employing medications and interventional brain stimulation techniques (VNS, TMS and others) to treat patients with psychiatric disease. In addition he serves as Director of Undergraduate Education in Bioengineering at Stanford, teaches yearly courses in both the graduate and undergraduate curricula, and provides education and training in optogenetics as well as freely distributing and supporting tools and expertise to thousands of scientists worldwide.

 
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