A barrage of information constantly assaults our senses, of which only a fraction is relevant at any given point in time. However, the neural circuitry supporting the suppression of irrelevant sensory distractors is not completely understood. The claustrum, a circuit hub with vast cortical connectivity, is an intriguing brain structure, whose restrictive anatomy, thin and elongated, has precluded functional investigation. Here, we describe the use of Egr2-CRE mice to access genetically defined claustral neurons. Utilizing conditional viruses for anterograde axonal labeling and retrograde trans-synaptic tracing, we validated this transgenic model for accessing the claustrum and extended the known repertoire of claustral input/output connectivity. Addressing the function of the claustrum, we inactivated CL Egr2+ neurons, chronically as well as acutely, in mice performing an automated two-alternative forced-choice behavioral task. Strikingly, inhibition of CL Egr2+ neurons did not significantly impact task performance under varying delay times and cue durations, but revealed a selective role for the claustrum in supporting performance in the presence of an irrelevant auditory distractor. Further investigation of behavior, in the naturalistic maternal pup-retrieval task, replicated the result of sensitization to an auditory distractor following inhibition of CL Egr2+ neurons. Initiating investigation into the underlying mechanism, we found that activation of CL Egr2+ neurons modulated cortical sensory processing, suppressing tone representation in the auditory cortex. This functional study, utilizing selective genetic access, implicates the claustrum in supporting resilience to distraction, a fundamental aspect of attention. Atlan, Terem, et al. describe the use of Egr2-CRE mice to access claustral projection neurons, identifying reciprocal connectivity throughout the brain. Silencing of CL Egr2+ neurons renders mice susceptible to an auditory distractor. Congruently, tone representation in the auditory cortex is suppressed by activation of CL Egr2+ neurons, suggesting an underlying mechanism.
Atlan, G., Terem, A., Peretz-Rivlin, N., Sehrawat, K., Gonzales, B. J., Pozner, G., … Citri, A. (2018). The Claustrum Supports Resilience to Distraction. Current Biology, 28(17), 2752-2762.e7. https://doi.org/10.1016/j.cub.2018.06.068