Brain serotonin determines maternal behavior and offspring survival

Abstract

Maternal care is an indispensable component of offspring survival and development in all mammals and necessary for reproductive success. Although brain areas regulating maternal behaviors are innervated by serotonergic afferents, very little is known about the role of this neurotransmitter in these behaviors. To evaluate the contribution of serotonin to maternal care, we used mice with a null mutation in the gene for tryptophan hydroxylase-2 (TPH2), which results in a genetic depletion of brain serotonin, and tested them in a wide range of maternal behavior paradigms. We found that litters born to and reared by TPH2 −/− mothers showed decreased survival, lower weaning weights and increased cannibalization. In addition, TPH2 −/− mothers performed poorly in pup retrieval, huddling, nest construction and high-arched back nursing. Aggression in TPH2 −/− dams was not triggered by lactation and was steadily high. Survival and weaning weight deficits of TPH2 −/− pups were rescued by cross-fostering and in litters of mixed genotype (TPH2 −/− and TPH2 −/+ ). However, the maternal behaviors of TPH2 −/− dams did not improve when rearing either TPH2 +/+ pups or mixed-genotype litters. In addition, TPH2 −/− pups significantly worsened the behavior of TPH2 +/+ dams with respect to cannibalism, weaning weight and latency to attack. Olfactory and auditory functions of TPH2 −/− females or anxiety-like behaviors did not account for these maternal alterations as they were equal to their TPH2 +/+ counterparts. These findings illustrate a profound influence of brain serotonin on virtually all elements of maternal behavior and establish that TPH2 −/− pups can engender maladaptive mothering in dams of both genotypes.

Neuronal serotonin in the regulation of maternal behavior in rodents

“…Brain areas critical for maternal behaviors in rodents include the MPOA, the BNST, the olfactory bulb and amygdala, all of which are directly innervated by serotonergic afferents arising in the raphe nuclei of the mesencephalon [8] . This is one of the main elements suggestive of an involvement of this neurotransmitter in maternal processes.…”

“…Pups born to mothers with a genetic depletion of TPH2 have deficits in survival and body weights [8,9] . In addition, TPH2 knockout mothers display increases in pup killing and disruptions in pup retrieval/huddling, nest building and high arched-back nursing, whereas they did not exhibit maternal aggression [8] . Strikingly, most of the behaviors used to assess maternal performance, if not all, are altered in females without brain serotonin.…”

“…However, these alterations were rescued by genetical restitution using the human ortholog of Pet-1 [10] . Both TPH2 and Pet-1 knockout dams appear to be inattentive to their young and alternated between digging/climbing behaviors and alternated traversal of the cage [8,10] . These outcomes correlate well with the increased compulsivity and impulsivity phenotypes associated to the lack of central serotonin [32] .…”

“…Although the role of serotonin in influencing maternal processes has been primarily associated with increases in the release of maternally-relevant hormones such as prolactin and oxytocin [6,7] more recent studies suggest that serotonin signaling surpasses an indirect regulation [8][9][10] . Studies have associated reductions in central serotonin transmission with significant deficits in survival and the growth rate of offspring, as well as with disruptions in maternal care and increases in pup killing [8][9][10][11] . This article aims to examine the basics of the components of maternal behaviors in rodents and the neural systems underpinning these maternal responses with special emphasis REVIEW on the role of neural serotonin in the regulation of these behaviors.…”

Testosterone might not be necessary to support female aggression in incubating northern cardinals

“…Considering that circulating T is present during periods when females of many species are aggressively defending nests, it is plausible that a relationship between T and avian maternal aggression could exist. Maternal aggression has been well studied in mammals (particularly rodents), and modulation of this behaviour has been linked to a number of hormones including oxytocin, vasopressin, progesterone and neurotransmitters such as serotonin (Angoa-P erez et al, 2014;Bosch & Neumann, 2012;Heiming et al, 2013;Kelly & Goodson, 2014;Sabihi, Dong, Durosko, & Leuner, 2014;de Sousa et al, 2010), but many of these hormones are also used in lactation, a process that birds do not undergo, and their links with aggression may be secondary to their main use. Here we compare circulating levels of T in female northern cardinals, Cardinalis cardinalis (hereafter 'cardinals'), that were defending their nest from a simulated conspecific intruder to better understand how T and avian maternal aggression covary.…”