Claustral Neurons Projecting to Frontal Cortex Mediate Contextual Association of Reward

• Published in: Current biology 2020-09, Vol.30 (18), p.3522-3532.e6
• Main Authors: Terem, Anna, Gonzales, Ben Jerry, Peretz-Rivlin, Noa, Ashwal-Fluss, Reut, Bleistein, Noa, del Mar Reus-Garcia, Maria, Mukherjee, Diptendu, Groysman, Maya, Citri, Ami
• Format: Article
• Language: English
• Subjects: claustrum; cocaine; conditioned-place preference; Drd1; frontal cortex; incentive salience; real-time conditioned-place preference; reward
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2020.06.064

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 claustral neurons by cocaine and their role in drug sensitization. In order to characterize the circuit within which these neurons are embedded, we apply chemo- and opto-genetic manipulation of increasingly specified claustral subpopulations. This strategy resolves the role of a defined network of claustrum neurons expressing dopamine D1 receptors and projecting to frontal cortex in the acquisition of cocaine conditioned-place preference and real-time optogenetic conditioned-place preference. In sum, our results suggest a role for a claustrum-to-frontal cortex circuit in the attribution of incentive salience, allocating attention to reward-related contextual cues. [Display omitted] •The claustrum receives dopamine inputs and expresses dopamine receptors•Claustral D1R+ cell activity is required for acquisition of cocaine preference•D1R+ neurons are a subset of frontal-projecting claustral neurons•Stimulation of claustrum D1R+/frontal-projecting cells drives context conditioning Terem et al. uncover the role of the claustrum in context reinforcement. They identify claustral dopamine D1-receptor-expressing neurons as a subpopulation of frontal-projecting claustral neurons important for de novo context reinforcement and the acquisition of cocaine preference.