The Mouse Claustrum Is Required for Optimal Behavioral Performance Under High Cognitive Demand

BACKGROUND: To achieve goals, organisms are often faced with complex tasks that require enhanced control of cognitive faculties for optimal performance. However, the neural circuit mechanisms underlying this ability are unclear. The claustrum is proposed to mediate a variety of functions ranging from sensory binding to cognitive control of action, but direct functional assessments of this telencephalic nucleus are lacking. METHODS: Here, we employed the Gnb4 (guanine nucleotide-binding subunit beta-4) cre driver line in mice to selectively monitor and manipulate claustrum projection neurons during 1-choice versus 5-choice serial reaction time task performance. RESULTS: Using fiber photometry, we found elevated claustrum activity prior to an expected cue during correct performance on the cognitively demanding 5-choice response assay relative to the less demanding 1-choice version of the task. Claustrum activity during reward acquisition was also enhanced when task demand was higher. Furthermore, optogenetically inhibiting the claustrum prior to the onset of the cue reduced choice accuracy on the 5-choice task but not on the 1-choice task. CONCLUSIONS: These results suggest that the claustrum supports a cognitive control function necessary for optimal behavioral performance under cognitively demanding conditions.