Corticotropin-releasing hormone (CRH) neurons within the paraventricular hypothalamic
nucleus (PVH) play a crucial role in initiating the neuroendocrine response to stress
and are also pivotal in coordination of autonomic, metabolic, and behavioral stress
reactions. Although the role of parvocellular CRHPVH neurons in activation of the
hypothalamic–pituitary–adrenal (HPA) axis is well established, the distribution and
function of CRH-expressing neurons across the whole central nervous system are less
understood. Stress responses activate complex neural networks, which differ depending
on the type of stressor and on the sex of the individual. Because of the technical
difficulties of localizing CRH neurons throughout the rodent brain, several CRH reporter
mouse lines have recently been developed. In this study, we used Crh-IRES-Cre;Ai9
reporter mice to examine whether CRH neurons are recruited in a stressor- or sex-specific
manner, both within and outside the hypothalamus. In contrast to the clear sexual
dimorphism of CRH-mRNA-expressing neurons, quantification of CRH-reporting, tdTomato-positive
neurons in different stress-related brain areas revealed only subtle differences between
male and female subjects. These results strongly imply that sex differences in CRH
mRNA expression occur later in development under the influence of sex steroids and
reflects the limitations of using genetic reporter constructs to reveal the current
physiological/transcriptional status of a specific neuron population. Next, we compared
the recruitment of stress-related, tdTomato-expressing (putative CRH) neurons in male
and female Crh-IRES-Cre;Ai9 reporter mice that had been exposed to predator odor.
In male mice, fox odor triggered more c-Fos in the CRH neurons of the paraventricular
hypothalamic nucleus, central amygdala, and anterolateral bed nucleus of the stria
terminalis compared to females. These results indicate that male mice are more sensitive
to predator exposure due to a combination of hormonal, environmental, and behavioral
factors.
