The claustrum-prefrontal cortex pathway regulates impulsive-like behavior

The claustrum connects with a broad range of cortical areas including the prefrontal cortex (PFC). However, the function of the claustrum (CLA) and its neural projections remains largely unknown. Here, we elucidated the role of the neural projections from the CLA to the PFC in regulating impulsivity in male rats. We first identified the CLA–PFC pathway by retrograde tracer and virus expression. By using immunofluorescent staining of the c-Fos-positive neurons, we showed that chemogenetic activation and inhibition of the CLA–PFC pathway reduced and increased overall activity of the PFC, respectively. In the 5-choice serial reaction time task (5-CSRTT), we found that chemogenetic activation and inhibition of the CLA–PFC pathway increased and reduced the impulsive-like behavior (i.e., premature responses), respectively. Furthermore, chemogenetic inhibition of the CLA–PFC pathway prevented methamphetamine-induced impulsivity, without affecting methamphetamine-induced hyperactivity. In contrast to the role of CLA–PFC pathway in selectively regulating impulsivity, activation of the claustrum disrupted attention in the 5-CSRTT. These results indicate that the CLA–PFC pathway is essential for impulsivity. This study may shed light on the understanding of impulsivity-related disorders such as drug addiction.