The claustrum as a central hub for reward and threat processing.

The claustrum (CLA) complex is composed of the CLA and the dorsal endopiriform nucleus. The CLA is a small, evolutionarily conserved brain structure situated between the striatum and insular cortex. Although the CLA is present in nearly all mammals, its precise anatomical delineation, particularly in rodents, remains poorly defined due to unclear boundaries with adjacent cortical regions. Interest in the CLA has augmented following the influential hypothesis proposed by Crick and Koch regarding its potential involvement in consciousness. Over the past two decades, accumulating evidence has implicated the CLA in a range of neural processes, including cortical information processing, sensory integration, anesthesia, regulation of sleep-wake cycles, and hallucinogenic effects. Notably, recent findings suggest that the CLA plays an important role in modulating both reward (appetitive) and threat (aversive) responses, two fundamental and antagonistic systems essential for organismal survival. For instance, the CLA may contribute to drug reward-related behaviors as well as threat conditioning and defensive responses. This review summarizes current anatomical and functional insights into the CLA and introduces a conceptual framework for understanding its contributions to reward and threat processing. We further review recent advances regarding the role of the CLA in regulating these processes and their relevance to psychiatric disorders such as drug addiction and post-traumatic stress disorder (PTSD). Finally, we outline several scientific questions for future research in this domain. In summary, despite a limited understanding of CLA function and circuitry in the context of reward and threat processing, existing data support the CLA's involvement in mediating related behaviors and associated psychiatric disorders.