Frontiers in Neuroendocrinology 53 (2019) 100747 Contents lists available at ScienceDirect Frontiers in Neuroendocrinology journal homepage: www.elsevier.com/locate/yfrne Challenges to the parental brain: Neuroethological and translational T considerations ⁎ Kelly G. Lamberta, , Elizabeth M. Byrnesb a Department of Psychology, University of Richmond, VA 23173, United States b Cummings School of Veterinary Medicine, Tufts University, N. Grafton, MA 01536, United States ABSTRACT Extending from research documenting adaptive parental responses in nonthreatening contexts, the influences of various neuroethological and physiological chal- lenges on effective parenting responses are considered in the current review. In natural habitats, rodent family units are exposed to predators, compromised resources, and other environmental stressors that disrupt HPA axis functions. With the additional physiological demands associated with caring for offspring, alterations in stress-related neuroendocrine responsiveness contribute to adaptive responses in many challenging contexts. Some environmental contexts, however, such as restricted nesting resources, result in disrupted maternal responses that have a negative impact on offspring wellbeing. Additionally, parental dysregulation associated with exposure to environmental chemicals or pharmacological substances, also compromise maternal responses with effects that often extend to future generations. Continued preclinical and clinical research elucidating parental responses to various stressors and physiological disruptors is necessary to provide valuable translational information identifying threats to effective parenting outcomes. 1. Introduction: The dynamic parental brain As female rats transform from a nulliparous to primiparous animal, many neurobehavioral changes occur to facilitate caregiving responses It is a commonly held belief that a woman’s intellectual capacity promoting the well-being of offspring. In contrast to humans who diminishes during pregnancy. Indeed, the term “baby brain” refers to benefit from diagnostic tests that allow them to cognitively prepare for the memory lapses and cognitive failures reported by many women not impending parenthood, most mammals rely exclusively on neurophy- only during pregnancy, but also during the postpartum period. A recent siological changes triggered by alterations in key reproductive hor- meta-analysis indicated a significant decline in cognitive function, mones. Critical to preparing the female for her new role, prolactin and particularly during the third trimester, between pregnant and non- associated placental lactogens facilitate the transformation from the pregnant women (Davies et al., 2018). Such effects are likely due to the nulliparous to the maternal brain (Grattan 2011), a response that is dramatic reorganization of the maternal brain occurring during preg- swift and consistent among maternal rodents (Fleming and Rosenblatt, nancy to prepare for the physiological and behavioral changes asso- 1974). Prolactin, perhaps best known for its role in milk production and ciated with becoming a mother. Yet, the experience of motherhood lactation, is essential for the emergence of maternal behavior. When greatly expands the behavioral repertoire of the female and may even prolactin receptors are compromised in the medial preoptic area of the improve cognitive capacity. Findings from both rodents and non-human hypothalamus (MPOA), aspects of maternal behavior, including pup primates suggest that new mothers are more vigilant (Kinsley et al., retrieval and nursing, are diminished (Brown et al., 2017). Ad- 1999), better at multitasking (Bardi et al., 2014), and bolder in their ditionally, both oxytocin and vasopressin, neuropeptides thought to pursuit of food than their virgin counterparts (Lambert et al., 2005; have evolved from the ancient precursor vasotocin (Francis et al., Kinsley et al., 2014). In other words, when challenged, mothers engage 2002), facilitate maternal and paternal affiliative responses directed in complex responses to nurture their genetic investments, and this new toward offspring and their care (Russell et al., 2001; Leng et al., 2008; orientation to the external environment is predicated upon a funda- Lambert et al., 2013; Bendesky et al., 2017). mental internal transition from nulliparity to motherhood (Kinsley These neurochemical changes, as well as others, influence the et al., 1999; Wartella et al., 2003; Love et al., 2005; Kinsley et al., emerging maternal neuroarchitecture, altering synaptic plasticity and 2014). The consideration of adaptive maternal responses, observed in consolidating neural circuits that support parental care. In addition to challenging and stressful contexts both in laboratory and natural set- the MPOA, the amygdala, medial prefrontal cortex, nucleus accumbens, tings, is of central importance in this review. superior-temporal gyrus, insula and areas of the parietal and frontal ⁎ Corresponding author at: Department of Psychology, Gottwald Science Center, B326, University of Richmond, Richmond, VA 23173, United States. E-mail address: [email protected] (K.G. Lambert). https://doi.org/10.1016/j.yfrne.2019.04.004 Received 3 November 2018; Received in revised form 15 March 2019; Accepted 16 April 2019 Available online 17 April 2019 0091-3022/ © 2019 Elsevier Inc. All rights reserved. K.G. Lambert and E.M. Byrnes Frontiers in Neuroendocrinology 53 (2019) 100747 gyrus have been implicated in human parental behavior, with structural compromise adequate care and the well-being of offspring. Although changes in the form of increased gray matter observed in the prefrontal the emphasis of this review is on the maternal brain, where appropriate, cortex, parietal lobe and midbrain areas (Kim et al., 2010; Atzil et al., paternal responses will also be considered. 2012). With regard to long-term changes associated with motherhood, reductions in gray matter in brain structures associated with social 2. Detecting Threats: The maternal stress response cognition have been reported, including changes in the superior tem- poral sulcus, medial and frontal cortex, hippocampus and cortical fu- With the arrival of pregnancy, the neurobiological cost-benefit siform areas (Barha and Galea, 2017; Hoekzema et al., 2017). Further, evaluations shift to ensure the survival of both mother and offspring. At rodent research has indicated structural changes associated with cell a time when there is more to lose from the perspective of genetic in- proliferation, including neurogenesis, within regions of the hippo- vestments, it is informative to consider alterations in the maternal an- campus across the peripartum period. Such changes may facilitate the imals’ stress response system. It has been known for over half a century changing responses associated with effective maternal care (Galea that the hypothalamic–pituitaryadrenal (HPA) response is attenuated, et al., 2014). rather than enhanced, during a time when it seems that a heightened Thus, many neurobiological transformations underlie the transition HPA response may be necessary for sufficient protection of the offspring to parenthood. It is interesting to consider that the same transforma- (Thoman et al., 1970; Barlow et al., 1975). Subsequent research has tions marking the evolution from nonparental to parental responses, indicated that circadian variations in HPA activity are muted (Atkinson including trasitions from nulliparity to primiparity, serve as signature and Waddell, 1995; Brunton et al., 2005), coincident with an atte- characteristics for the evolution of mammals. In his book The Triune nuated response to many environmental stressors (Douglas et al., 1995; Brain, pioneering neuroanatomist Paul MacLean observed the im- Brunton et al., 2008), which may serve to limit the energetic costs as- portance of this transformational shift as he identifited three behaviors sociated with sympathetic activation during a time of increased energy that separated mammals from other vertebrates, including nursing, expenditure for the mother. Further, attenuated glucocorticoid pro- audiovocal maternal-offspring communications and the emergence of duction serves to limit fetal exposure thereby avoiding any potential play behavior. Interestingly, all of these behaviors are associated with adverse neurodevelopmental effects of these potent steroidal hormones the emergence of maternal behavior (MacLean, 1990; Lambert, 2003). (Brunton and Russell, 2008; Brunton et al., 2008). MacLean’s observations were recently corroborated by evidencethat a In addition to the endocrine modifications accompanying pregnancy mammalian fore-runner species, Kayentatherium wellesi, a plant-eating and lactation, maternal experience itself alters behavioral responses to animal the size of a small dog that lived approximately 185 million stress. For example, when pup-sensitized (e.g., virgin females condi- years ago in the era of dinosaurs, gave birth to large litters of offspring tioned to care for pups) were exposed to a brightly-lit, noisy, open field without the facial and cranial enlargements typical of mammalian arena, they exhibited decreased anxiety-like behaviors similar to that morphology. Preserved fossils of one clutch revealed 38 offspring in this observed in animals that had previously experienced pregnancy and stem-mammalian perinate indicating that the offspring skulls had the lactation . Interestingly, this shift toward more risk-taking, less anxiety- same proportions as the