Abstract
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 CLEgr2+ neurons, chronically as well as acutely, in mice performing an automated two-alternative forced-choice behavioral task. Strikingly, inhibition of CLEgr2+ 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 CLEgr2+ neurons. Initiating investigation into the underlying mechanism, we found that activation of CLEgr2+ 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 CLEgr2+ neurons renders mice susceptible to an auditory distractor. Congruently, tone representation in the auditory cortex is suppressed by activation of CLEgr2+ neurons, suggesting an underlying mechanism.
Original language | American English |
---|---|
Pages (from-to) | 2752-2762.e7 |
Journal | Current Biology |
Volume | 28 |
Issue number | 17 |
DOIs | |
State | Published - 10 Sep 2018 |
Bibliographical note
Funding Information:The authors thank their friends and colleagues for their comments, especially Dr. Mickey London. We are indebted to Dr. Naomi Book-Melamed, head of the microscopy unit at the Life Science Institute, for technical support and access to software. Work in the Citri lab is funded by the Edmond and Lily Safra Center for Brain Sciences (ELSC), the Brain and Behavior Foundation (NARSAD 18795), the German-Israel Foundation (GIF 2299-2291.1/2011), the Binational Israel-USA Foundation (BSF 2011266), an EU Marie Curie Career Integration Grant (CIG PCIG13-GA-2013-618201), the Israel Anti-Drug Authority, the Israel Science Foundation (ISF 393/12), the National Institute for Psychobiology in Israel founded by the Charles E. Smith family (109-15-16), an Adelis Award for Advances in Neuroscience, the European Research Council (ERC-CoG 770951), a seed grant from the Eric Roland Fund for interdisciplinary research administered by the ELSC, and contributions from anonymous philanthropists in Los Angeles and Mexico City. A.C. is a supported member of the Israeli Center for Research Excellence (iCORE) program of the Israel Science Foundation (1796/12) and the Canadian Institute for Advanced Research Program in Child and Brain Development.
Funding Information:
The authors thank their friends and colleagues for their comments, especially Dr. Mickey London. We are indebted to Dr. Naomi Book-Melamed, head of the microscopy unit at the Life Science Institute, for technical support and access to software. Work in the Citri lab is funded by the Edmond and Lily Safra Center for Brain Sciences (ELSC), the Brain and Behavior Foundation ( NARSAD 18795 ), the German-Israel Foundation ( GIF 2299-2291.1/2011 ), the Binational Israel-USA Foundation ( BSF 2011266 ), an EU Marie Curie Career Integration Grant ( CIG PCIG13-GA-2013-618201 ), the Israel Anti-Drug Authority , the Israel Science Foundation ( ISF 393/12 ), the National Institute for Psychobiology in Israel founded by the Charles E. Smith family ( 109-15-16 ), an Adelis Award for Advances in Neuroscience , the European Research Council ( ERC-CoG 770951 ), a seed grant from the Eric Roland Fund for interdisciplinary research administered by the ELSC, and contributions from anonymous philanthropists in Los Angeles and Mexico City. A.C. is a supported member of the Israeli Center for Research Excellence (iCORE) program of the Israel Science Foundation ( 1796/12 ) and the Canadian Institute for Advanced Research Program in Child and Brain Development .
Publisher Copyright:
© 2018 Elsevier Ltd
Keywords
- attention
- auditory cortex
- chemogenetics
- claustrum
- cortical gain
- distraction
- fiber photometry
- optogenetics
- sensory selection
- transgenic