Discovery Using Optogenetics May Help Fine-Tune Treatments for Schizophrenia Symptoms

Karl Deisseroth, M.D., Ph.D., Stanford University, brain research expert and inventor of optogenetics
Karl Deisseroth, M.D., Ph.D.
Rewards can be powerful teachers, but it is actually the surprising moments—when an anticipated reward does not come, or when one arrives unexpectedly—that drive the brain to learn. The brain chemical dopamine has been thought to be involved in this process, playing the role of flagging “prediction errors” (the difference between what is expected and what actually happens) and providing a kind of “uh-oh” moment that alerts the brain to change course―find a different model of the world or plan of action―in order to get a reward. This function and timing of dopamine release for prediction error learning is thought to malfunction in schizophrenia. Innocuous events in a person’s life, for example, can be mistakenly flagged as important, and provide grist for delusions and hallucinations.
A new study using animal models and the revolutionary technology optogenetics, published May 26, 2013 in Nature Neuroscience, offers the first direct causal evidence of the role of dopamine neuron signaling in prediction error learning. To study this, researchers at the University of California, San Francisco, used optogenetics to manipulate dopamine neuron activity in animal models during behavioral learning experiments. Optogenetics is a fiber-optic technology that enables precise stimulation or inhibition of specific neurons in the brain and allows for observation of the corresponding behavior in living animals, developed with the support of a Brain & Behavior Research Foundation NARSAD Grant by Karl Deisseroth, M.D., Ph.D. of Stanford University (one of the authors of the current paper). 
The researchers found that stimulation of dopamine neurons at certain times could alter the learning from prediction errors and could also effectively mimic a prediction error, with a long-lasting impact on reward-seeking behavior. This unique ability offered by optogenetics to directly observe behavioral response from dopamine neuron signaling establishes a causal role of dopamine in prediction error learning. The new findings demonstrate the importance of precisely timed dopamine release and offer guidance for the development of treatments to more effectively treat the related symptoms of schizophrenia.