Thalamic neuropeptide mediating the effects of nursing on lactation and maternal motivation

Abstract

SUMMARY Nursing has important physiological and psychological consequences on mothers during the postpartum period. Tuberoinfundibular peptide of 39 residues (TIP39) may contribute to its effects on prolactin release and maternal motivation. Since TIP39-containing fibers and the receptor for TIP39, the parathyroid hormone 2 receptor (PTH2 receptor) are abundant in the arcuate nucleus and the medial preoptic area, we antagonized TIP39 action locally to reveal its actions. Mediobasal hypothalamic injection of a virus encoding an antagonist of the PTH2 receptor markedly decreased basal serum prolactin levels and the suckling-induced prolactin release. In contrast, injecting this virus into the preoptic area had no effect on prolactin levels, but did dampen maternal motivation judged by reduced time in a pup-associated cage during a place-preference test. In support of an effect of TIP39 on maternal motivation, we observed that TIP39 containing fibers and terminals had the same distribution within the preoptic area as neurons expressing Fos in response to suckling. Furthermore, TIP39 terminals closely apposed the plasma membrane of 82% of Fos-ir neurons. Retrograde tracer injected into the arcuate nucleus and the medial preoptic area labeled TIP39 neurons in the posterior intralaminar complex of the thalamus (PIL), indicating that these cells but not other groups of TIP39 neurons project to these hypothalamic regions. We also found that TIP39 mRNA levels in the PIL markedly increased around parturition and remained elevated throughout the lactation period, demonstrating the availability of the peptide in postpartum mothers. Furthermore, suckling, but not pup exposure without physical contact, increased Fos expression by PIL TIP39 neurons. These results indicate that suckling activates TIP39 neurons in the PIL that affect prolactin release and maternal motivation via projections to the arcuate nucleus and the preoptic area, respectively.

Neuroendocrine regulation of maternal behavior

“…Recent studies have identified a role for a 39 residue tuberoinfundibular peptide (TIP39) in the rat that binds to the parathyroid 2 receptor in both the MPOA and arcuate region in regulating suckling-induced prolactin secretion (Cservenák et al, 2010) and more recently maternal motivation (Cservenák et al, 2013). Retrograde studies by these investigators have identified that TIP39 producing cells that project to the arcuate region and medial preoptic area are located in the posterior intralaminar complex of the thalamus.…”

Tuning the brain for motherhood: prolactin-like central signalling in virgin, pregnant, and lactating female mice

“…These regions comprise several nodes of the sociosexual brain: the LSV, the MePD, BSTMPM, AC/ADP, MPO, VMHvl and adjoining tuberal region (hypothalamic aggression locus), and VLPAG (Newman 1999). We also included the magnocellular neurosecretory nuclei (Pa and SO) and other sites that are also involved in the regulation of maternal behaviours (CeM, AVPe, and PIL; Bosch and Neumann 2010;Scott et al 2015) or related aspects of motherhood (Cservenák et al 2013), despite not being usually considered as part of the sociosexual brain network. Finally, we also analysed the Arc, given its role in the feedback control of hypophyseal PRL release (Ben-Jonathan and Hnasko 2001; Sapsford et al 2012).…”

“…4f). This region is known to be a relay station for ascending somatosensory information of the ventral region of the body, which allows suckling stimulation to trigger the release of PRL during lactation (Cservenák et al 2013). Therefore, it is tempting to suggest a role of pSTAT5-ir in this region in feedback regulation of suckling-induced PRL release through a central modulation of sensitivity to suckling stimulation.…”

“…Nonetheless, contact with pups and the correct processing of pup-derived stimuli, such as suckling stimulation conveyed by the PIL (Cservenák et al 2010(Cservenák et al , 2013 or chemosignal stimuli processed by the MePD (Pardo-Bellver et al 2012), may be major factors in the maintenance (rather than the onset) of maternal aggression. In fact, information derived from pup chemosignals and from suckling stimulation may converge in the medial amygdala, since it receives projections from the main and accessory olfactory bulbs and the PIL (Cádiz- Moretti et al 2016).…”

Maternally involved galanin neurons in the preoptic area of the rat

“…Evidence suggests that TIP39-expressing neurons regulate prolactin release via their projections to the arcuate nucleus (Cservenak et al 2010; Dobolyi et al 2010). TIP39, a neuropeptide originally purified from the hypothalamus (Usdin et al 1999), may also contribute to the control of maternal motivation (Cservenak et al 2013). Therefore, we examined the possible connection between TIP39 and preoptic galanin neurons by comparing their topographical distributions.…”