Developmental specification and adult cellular plasticity of oxytocin and vasopressin systems

The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are closely related neurohypophyseal peptides that play critical roles in regulating complex animal behaviors and homeostatic functions. Both neuropeptides are mainly synthetized at specific hypothalamic nuclei, such as the paraventricular and suprachiasmatic nucleus (PVN and SON), among others. Our previous work (Madrigal & Jurado, 2021) revealed that distinct OXT and AVP nuclei are developed independently and most of them show a significant number of neurons co-expressing OXT and AVP during early postnatal stages (PN7) coinciding with a critical period for social interaction. This mixed population, of OXT+/AVP+ neurons drastically decline in the adult brain suggesting cellular plasticity is developmentally regulated. Using brain clearing techniques (iDISCO+ ) and 3D imaging, we analyzed whether OXT and AVP systems also exhibit plastic properties in the adult brain. Our results indicate that certain nuclei undergo cellular plasticity in a sex and motherhood dependent manner obtaining the most prominent phenotypes in the periventricular nucleus (PeVN) (sex-dependent), and the SON and retrochiasmatic area (RCH) in which OXT and AVP plasticity is mainly motherhood-dependent. Furthermore, sexual experience induces an increase of tyrosine hydroxylase (TH) expression levels in a subpopulation of OXT and AVP neurons in the RCH. Our findings provide new information to understand the specification of neuropeptidergic systems during development and their plastic properties upon critical life events in the adult animal.