Brain-Wide Patterns of CRF Receptor 1 Expression in the Transgenic CRFR1-Cre-2a-tdTom Rat

The ability to manipulate neurons that express corticotropin-releasing factor (CRF) or its receptors has led to many new discoveries about how CRF signaling modulates stress-related behaviors in mice. However, similar advances in rats have been limited by the lack of reporter lines targeting CRF receptors, restricting access to behavioral paradigms that are more suitable for, or specific to, rats. Here, we provide an extensive neuroanatomical characterization of a recently generated CRFR1-Cre rat. We show that Cre and tdTomato are expressed in a pattern that closely aligns with previously reported CRFR1 expression patterns, as determined by in situ hybridization in rats and by genetic labeling in CRFR1 transgenic mice. We detail expression patterns at multiple rostrocaudal levels to validate the use of this transgenic rat in multiple neural circuits that signal via CRF activation of CRFR1. Furthermore, we demonstrate that expression of Cre recombinase, combined with viral vector delivery, can be used to trace CRFR1-expressing neurons and their axonal terminals in target regions. This study is intended to serve as a resource for examining the expression pattern of CRFR1 and as a validation of the CRFR1-Cre rat for reliable use with Cre-dependent viral approaches to manipulate and/or record the activity of CRFR1-expressing neurons in distinct brain regions. We expect that the availability of the CRFR1-Cre rat, along with an increasing number of transgenic rat lines, will further expand our understanding of how CRF transmission mediates stress responses by leveraging the behavioral strengths of the rat as a model system.