Similarities of neocortical deep layer Oprk1-positive neurons and claustrum neurons in connectivity and activity

The claustrum (CLA) is densely connected to the cortex and plays a critical role in synchronized brain states, including sleep, anesthesia, and epilepsy. Although claustrum gene expression patterns differ from those of the cortex, a subset of deep-layer cortical neurons share the claustrum's transcriptomic profile and marker genes, such as Oprk1 and Nurr1. However, little is known about the connectivity and function of these claustrum-like cortical (CLC) neurons. Using Oprk1-cre transgenic rats and cre-dependent viral tracing, we systematically compared the whole-brain connectivity of CLC and CLA neurons. We found that both CLC and CLA neurons are primarily connected to the cortex. However, while the claustrum shows widespread projections to midline and limbic cortices, CLC neurons project more densely to the sensory cortex. Both cell types show increased c-Fos expression in novel environments and synchronized activity under anesthesia. These findings suggest that CLC neurons form a parallel and complementary cortical microcircuit alongside the claustrum.