A Claustro-Frontal Dopamine-Driven Circuit Essential For Contextual Association of Reward

Abstract

The claustrum is a small nucleus, exhibiting vast reciprocal connectivity with cortical, subcortical and midbrain regions. Recent studies, including ours, implicate the claustrum in salience detection and attention. In the current study, we develop an iterative functional investigation of the claustrum, guided by quantitative spatial transcriptional analysis. Using this approach, we identify a circuit involving dopamine-receptor expressing claustral neurons projecting to frontal cortex necessary for context association of reward. We describe the recruitment of the claustral dopamine system by cocaine and its essential role in drug sensitization. Applying chemo- and opto- genetic manipulation of increasingly specified claustral subpopulations, we identify a role for a defined network of claustrum neurons in the acquisition of contextual cocaine reward and de novo context reinforcement. In sum, our results identify a role for a dopamine-driven claustro-frontal neural circuit in the attribution of incentive salience, allocating contextual attention to reward-related cues.

Keywords: Claustrum, incentive salience, reward, reinforcement, dopamine, cocaine, behavioral sensitization, conditioned-place preference, Drd1, Real time conditioned-place preference