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.

Keywords: Critical period; Development; Oxytocin; PVN; Prairie vole; Vasopressin.

Fig. 1

Schematic representation of treatment groups. Family units were randomly assigned to one of three conditions: together, isolate, or reunite. The same procedure was used for family units with pups of each age (PND2, PND9, or PND21). See text for details. HC home cage, NC novel cage

Fig. 2

a Mean (± SEM) number of Fos immunoreactive (ir) neurons in the rostral paraventricular nucleus of the hypothalamus (PVN) for PND2, PND9, and PND21 pups that were Isolated (light blue), Reunited (dark blue), or Together (gray) for 1.5 h. *Indicates p ≤ 0.05. b Mean (± SEM) number of Fos immunoreactive (ir) neurons in the caudal PVN for PND2, PND9, and PND21 pups that were isolated, reunited, or together for 1.5 h

Fig. 3

Mean (± SEM) number of Fos immunoreactive (ir) neurons in the medial preoptic nucleus (MPO) for PND2, PND9, and PND21 pups that were isolated (light blue), reunited (dark blue), or together (gray) for 1.5 h. *Indicates p ≤ 0.05

Fig. 4

Representative immunocytochemical staining of VP (green; Alexa Fluor 488), OT (pseudo-colored blue; Alexa Fluor 680), and Fos (red; Alexa Fluor 594) in the a rostral PVN and b caudal PVN of a PND9 male in the Together condition. Scale bar = 100 μm

Fig. 5

Representative immunocytochemical staining of VP (green; Alexa Fluor 488) in the rostral PVN of PND9 male subjects in the a isolate, b reunite, and c together conditions

Fig. 6

a Mean (± SEM) number of vasopressin (VP) immunoreactive (ir) neurons in the rostral portion of the paraventricular nucleus of the hypothalamus (PVN) for PND2, PND9, and PND21 pups that were Isolated (light blue), Reunited (dark blue), or Together (gray) for 1.5 h. *Indicates p ≤ 0.05. b Mean (± SEM) number of VP-ir neurons in the caudal portion of the PVN for PND 2, PND9, and PND21 pups that were isolated, reunited, or together for 1.5 h

Fig. 7

Mean (± SEM) number of oxytocin (OT) immunoreactive (ir) neurons in the paraventricular nucleus of the hypothalamus (PVN; rostral and caudal levels combined) for PND2, PND9, and PND21 pups that were Isolated (light blue), Reunited (dark blue), or Together (gray) for 1.5 h. *Indicates p ≤ 0.05