Thursday, December 31, 2015

The New Neurosciences: Preclinical Optogenetic fMRI of Reward Circuitry

The Neurocomplimenter has come out of retirement to briefly praise a massive (13 pages + 83 page supplement) new tour de force by Ferenczi et al. (2015). The collaborative Stanford/Cornell team with departmental affiliations in Bioengineering, Neurosciences, Neurobiology & Behavior, Psychology, Psychiatry, Neurosurgery, and Radiology modeled the scourge of anhedonia (inability to experience pleasure) using a combination of optogenetics and fMRI in awake rats.


Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions.


Emily A. Ferenczi, Kelly A. Zalocusky, Conor Liston, Logan Grosenick, Melissa R. Warden, Debha Amatya, Kiefer Katovich, Hershel Mehta, Brian Patenaude, Charu Ramakrishnan, Paul Kalanithi, Amit Etkin, Brian Knutson, Gary H. Glover, Karl Deisseroth.  Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behaviorScience 1 January 2016. DOI: 10.1126/science.aac9698

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