Exploring the Regulatory Mechanism of Stress Responses in the Paraventricular Nucleus of the Hypothalamus: Backgrounds and Future Perspectives of Corticotropin-Releasing Factor-Modified Yellow Fluorescent Protein-Knock-In Mouse

Abstract

Corticotropin-releasing factor (CRF) plays a central role in the stress response by regulating the hypothalamic- pituitary-adrenal axis. In order to unravel unsolved issues underlying the regulatory mechanisms for CRF neurons, modified yellow fluorescent protein (Venus) gene was inserted into the CRF gene in frame, and CRF neurons were visualized by the Venus fluorescence. Venus expression is overlapped with CRF expression in most brain regions, including the paraventricular nucleus of the hypothalamus (PVH). This mouse is a useful tool especially for conducting electrophysiological recordings from CRF neurons. In the first half of the present review, the backgrounds of the generation of the mouse are described based on the previous literature: first, the anatomical distribution of CRF-immunoreactive neurons in the rat brain is overviewed, and then the knowledge on the electrophysiological properties of the parvocellular neuroendocrine neurons that constitute a subpopulation of neurons in the PVH (including PVH-CRF neurons) is described. These sections may help the readers in understanding the purpose of generating the CRF-Venus mouse. In the second half of the manuscript, the distribution of Venus-expressing neurons is characterized in the CRF-Venus mouse, and preliminary results of electrophysiological recordings from the Venus-expressing neurons are shown. CRF driver mouse lines are also referred to as a means for the CRF neuron-selective gene transfer or targeting. Novel mouse lines may serve as tools for disclosing the regulatory mechanisms for CRF neurons in the PVH, as well as other brain regions.