Rapid nonapeptide synthesis during a critical period of development in the prairie vole: plasticity of the paraventricular nucleus of the hypothalamus

Abstract

Vasopressin (VP) and oxytocin (OT) are involved in modulating basic physiology and numerous social behaviors. Although the anatomical distributions of nonapeptide neurons throughout development have been described, the functional roles of VP and OT neurons during development are surprisingly understudied, and it is unknown whether they exhibit functional changes throughout early development. We utilized an acute social isolation paradigm to determine if VP and OT neural responses in eight nonapeptide cell groups differ at three different stages of early development in prairie voles. We tested pups at ages that are representative of the three rapid growth stages of the developing brain: postnatal day (PND)2 (closed eyes; poor locomotion), PND9 (eye opening; locomotion; peak brain growth spurt), and PND21 (weaning). Neural responses were examined in pups that (1) were under normal family conditions with their parents and siblings, (2) were isolated from their parents and siblings and then reunited, and (3) were isolated from their parents and siblings. We found that VP and OT neural activity (as assessed via Fos co-localization) did not differ in response to social condition across development. However, remarkably rapid VP and OT synthesis in response to social isolation was observed only in the paraventricular nucleus of the hypothalamus (PVN) and only in PND9 pups. These results suggest that PVN nonapeptide neurons exhibit distinct cellular properties during a critical period of development, allowing nonapeptide neurons to rapidly upregulate peptide production in response to stressors on a much shorter timescale than has been observed in adult animals.

Paternal deprivation impairs social behavior putatively via epigenetic modification to lateral septum vasopressin receptor

“…These early-life experiences include maternal separation (19), father removal (8,15), communal rearing (2), and neonatal handling (20). The quantity of VP, OT, V1aR, and OTR throughout the forebrain shows profound plasticity over the course of development (21,22), indicating the raw potential upon which social or environmental interventions could modify neural phenotype. Moreover, social and/or spatial environmental complexity also has the capacity to alter the density of V1aR and OTR in the brain (21).…”

Age‐specific and context‐specific responses of the medial extended amygdala in the developing prairie vole

“…To assess whether meEA function changes across development, we conducted an IEG experiment utilizing a 3 × 3 design (see Kelly et al, 2018). We tested animals that were at three different stages of early development: PND 2, PND 9, and PND 21.…”

Oxytocin receptor gene loss influences expression of the oxytocin gene in C57BL/6J mice in a sex‐ and age‐dependent manner

“…In response to social isolation, prairie vole pups show enhanced c‐Fos activity and OXT immunoreactivity in the PVN at P9. This increase can be interpreted as either an increase in OXT production in response to a stressor or abnormally low levels of OXT release during social isolation at this age . Sensory deprivation by whisker removal or dark‐rearing of C57BL/6J mice since birth reduces Oxt mRNA and OXT peptide in the PVN, as well as OXT levels in the CSF .…”

“…This increase can be interpreted as either an increase in OXT production in response to a stressor or abnormally low levels of OXT release during social isolation at this age. 22 Sensory deprivation by whisker removal or dark-rearing of C57BL/6J mice since birth reduces Oxt mRNA and OXT peptide in the PVN, as well as OXT levels in the CSF. 23 Conversely, mice reared in an enriched environment from birth to P14 show increased Oxt mRNA levels in the hypothalamus, as well as increased OXT peptide signalling levels in the somatosensory cortex and visual cortex, at P14.…”