The Neurobiology of Addiction Research Center (NARC)
Project 3 - Selective Cortical Networks in Cocaine Seeking
Relapse is a persistent problem in cocaine addiction, and many important aspects of the brain mechanisms involved remain unknown. One key area for cocaine relapse is the medial prefrontal cortex (mPFC); in particular, mPFC interactions with the nucleus accumbens (NA) and ventral tegmental area (VTA) are critical for reinstatement of extinguished cocaine seeking. Projects 1 and 2 in this center focus on molecular and cellular mechanisms involved in the mPFC-to-NA pathway during extinction and reinstatement. Little is known about the activities of neurons in mPFC that project to NA, or that receive dopamine (DA) from VTA, during these cocaine behaviors. Here, we will use Fos labeling and unit recording during extinction and reinstatement to measure impulse activity of mPFC neurons identified as projecting to NA core or shell. We also will capitalize on TH::Cre rats and optogenetics methods recently implemented in our lab to determine the influence of endogenous DA release on impulse activity of prelimbic cortex neurons that project to NA core during extinction and reinstatement. Together, these studies will provide an overall map of NA-projecting mPFC neurons that are activated during cocaine behaviors, and also measure their impulse activities with respect to specific task stimuli and behaviors during exinction or reinstatement of cocaine seeking. These findings will provide a detailed circuit analysis of behavior-related activities in these key mPFC neurons that will be important information to extend results of molecular- and cellular-level studies in other projects of this center.
The Aston-Jones lab received Th-Cre progenitor female rats from Karl Deisseroth in 2011, and has established a robust breeding colony that produces TH-Cre offspring. These TH-Cre rats are now being used by NARC personnel and others at MUSC to study selectively the role of catecholamine brain systems in addiction and other behaviors. DREADD designer receptor expression (red) in ventral VTA of a TH-Cre rat. Mahler unpublished.
Fos-activated afferents to VTA following cue-ionduced reinstatement of cocaine seeking. Mahler SV, Aston-Jones GS (2012) Fos Activation of Selective Afferents to Ventral Tegmental Area during Cue-Induced Reinstatement of Cocaine Seeking in Rats. Journal of Neuroscience 32:13309–13325.