Neuroanatomical characterization of Gαi 2 -expressing neurons in the hypothalamic paraventricular nucleus of male and female Sprague-Dawley rats

Hypertension is a global health burden. The hypothalamic paraventricular nucleus (PVN) is an essential component of the neuronal network that regulates sodium homeostasis and blood pressure (BP). Previously, we have shown PVN-specific G protein-coupled receptor-coupled Gαi subunit proteins are essential to counter the development of salt-sensitive hypertension by mediating the sympathoinhibitory and natriuretic responses to increased dietary sodium intake to maintain sodium homeostasis and normotension. However, the cellular localization and identity of PVN Gαi -expressing neurons are currently unknown. In this study using in situ hybridization, we determined the neuroanatomical characterization of Gαi -expressing PVN neurons in 3-mo-old male and female Sprague-Dawley rats. We observed that Gαi -expressing neurons containing mRNA are highly localized in the parvocellular region of the hypothalamic PVN. At level 2 of the hypothalamic PVN, mRNA colocalized with ∼ 85% of GABA-expressing neurons and ∼28% of glutamatergic neurons. Additionally, within level 2 mRNA colocalized with ∼75% of corticotrophin-releasing hormone PVN neurons. neurons had lower colocalization with tyrosine hydroxylase (∼33%)-, oxytocin (∼6%)-, and arginine vasopressin (∼10%)-expressing parvocellular neurons in level 2 PVN. Colocalization was similar among male and female rats. The high colocalization of mRNA with GABAergic neurons, in conjunction with our previous findings that PVN Gαi proteins mediate sympathoinhibition, suggests that Gαi proteins potentially modulate GABAergic signaling to impact sympathetic outflow and BP.