1. Chapter 51 © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition Parenting Behavior

2. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 2 FIGURE 51.1 Mean and range of the number of days of pup exposure for nulliparous female rats to begin retrieving pups. Females were exposed to pups alone (Pup Induced), were exposed to pups after receiving an injection of blood plasma from a recently parturient and maternal female (M → V Injection), or were exposed to pups during and after a 6 h transfusion of blood from a recently parturient and maternal female (M → V Transfusion). Transfusion from a parturient female very rapidly induced retrieval in the nulliparous rats. Source: Modified from Terkel and Rosenblatt, 1972. 10

3. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 3 FIGURE 51.2 Duration of time (Mean + SEM) that suckled and nonsuckled postpartum rats, and maternally sensitized nulliparous rats, took to retrieve each pup to the nest (top panel) and spent licking the pups (bottom panel). Different letters above bars indicate significant differences between groups. Maternally sensitized nulliparous rats were deficient in both measures compared to postpartum mothers. Source: Modified from Lonstein et al., 1999. 107

4. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 4 FIGURE 51.3 Schematic representation of circulating plasma levels of estradiol (EST), progesterone (PROG), and prolactin (PRL) across pregnancy and parturition in laboratory rats, laboratory mice, and sheep. Source: Modified from Rosenblatt and Siegel, 1981. 102

5. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 5 FIGURE 51.4 Duration of time (Mean + SEM) spent licking the pups by adrenalectomized, postpartum rats that received various doses of corticosterone in their drinking water. *Significantly more pup licking compared to dams that received no replacement corticosterone. Source: Modified from Rees and Fleming, 2004. 101

6. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 6 FIGURES 51.5 [ 125 I]OTA binding in the mPOA and BSTv (adjacent brain sites critical for active maternal behaviors; see the section Hormones Most Significant for the Onset of Maternal Behavior) of postpartum female rats that had previously displayed high or low maternal responsivity (i.e., high or low licking and nursing). Highly responsive females had greater [ 125 I]OTA binding in both brain sites compared to less responsive females. Source: Modified from Champagne et al., 2001. 108

7. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 7 FIGURE 51.6 Schematic representation of circulating plasma levels of estradiol and progesterone across pregnancy and parturition in humans. Note that the levels of progesterone shown are divided by a factor of 10. For example, the immediate prepartum progesterone level is actually approximately 500 nmol/l. Source: Modified from Brett and Baxendale, 2001. 749

8. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 8 FIGURE 51.7 Correlation between salivary cortisol and the hedonic ratings (i.e., how pleasant or unpleasant) made by first-time mothers about the odor from their own infant’s shirt. Mothers with higher cortisol rated the odors as more pleasant. Source: Modified from Fleming et al., 1997. 232

9. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 9 FIGURE 51.8 Circulating testosterone (Mean +/- SEM) in male California mice before pairing with a female (Baseline), an hour after pairing (Courtship), 3 weeks after pairing (Bonded), and 4 days after the birth of their pups (Paternal). Source: Modified from Gleason and Marler, 2010. 288 Percentage of male wild- type (C57BL/6) and progesterone receptor knockout (PRKO) mice committing infanticide after the birth of their first or second litters. PRKO mice do not attack pups. Source: Modified from Schneider et al., 2003. 316

10. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 10 FIGURE 51.9 Percentage of male wild-type (C57BL/6) and progesterone receptor knockout (PRKO) mice committing infanticide after the birth of their first or second litters. PRKO mice do not attack pups. Source: Modified from Schneider et al., 2003. 316

11. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 11 FIGURE 51.10 Percentage of male Djungarian hamsters that ever retrieved a pup, and their highest overall parental responsiveness score, after administration of vehicle or bromocryptine for the 3 days before birth of their pups via subcutaneous injection (top panels) or chronically via osmotic minipumps (bottom panels). Prolactin suppression had no effect on paternal responding. Source: Modified from Brooks and Wynne-Edwards, 2005. 347

12. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 12 FIGURE 51.11 Plasma concentrations of testosterone, prolactin, and cortisol in human fathers before and after the birth of their infant. Different letters at base of bars indicate significant differences compared to the early prenatal group. Source: Modified from Storey et al., 2000. 369

13. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 13 FIGURE 51.12 Mean latency for nulliparous female rats to display maternal behavior after receiving cuts to the vomeronasal nerve (VN), olfactory bulb (OB), or both (VN–OB). Control animals received a sham section of the VN or OB. Note the particularly fast sensitization in the VN–OB females. Source: Modified from Fleming et al., 1979. 420

14. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 14 FIGURE 51.13 Sensory events regulating maternal behavior in laboratory rats. In this dyadic interaction, distal cues from pups elicit maternal contact seeking, which then permits the mother to receive perioral tactile inputs required for retrieval. Perioral tactile cues that dams receive while in the nest, mostly obtained while licking the pups, maintain her interest in interacting with the litter and stimulate the litter to search for nipples. Once a sufficient number of pups attach to nipples and begin suckling, these ventral inputs that the dam receives elicit her to show prolonged bouts of quiescent nursing and eventually let down milk. Sated pups will detach from nipples, and the loss of suckling inputs will often result in either the dam resuming active maternal behaviors while hovering over the litter or the dam leaving the nest. Source: Modified from Stern, 1996. 73

15. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 15 FIGURE 51.14 Frequencies of maternal behaviors (Median ± SIQR) shown by female rats tested early postpartum (days 7 and 8) or late postpartum (days 13 and 14) after transient inactivation of the mPOA with 2% bupivacaine or no inactivation by infusing saline. The behavioral control group received no stereotaxic surgery or infusion. Inactivating the mPOA disrupted all measures of active maternal behavior when performed early postpartum, but facilitated the same behaviors when performed late postpartum, indicating the differing role of the mPOA for maternal behavior across the postpartum period. Source: Modified from Pereira and Morrell, 2009. 506

16. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 16 FIGURE 51.15 Schematic representation of frontal sections through the postpartum rat medial preoptic area (mPOA) and ventral bed nucleus of the stria terminalis (BSTv) showing the location of Fos- immunoreactive (left) and FosB-immunoreactive (right) cells after no interaction with pups (left half of each panel) and after an interaction with pups and the display of maternal behavior (right half of each panel). Ac: anterior commissure; oc: optic chiasm. Source: Modified from Numan et al., 2006. 4

17. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 17 FIGURE 51.16 Changes in dopamine (DA) signaling in the shell of the nucleus accumbens of two representative high-licking and low-licking postpartum rats before, during, and after a bout of licking their pups. The gray bar indicates the duration of the licking bout. Note the greater increase in high-licking rats and that the rise in DA signaling begins to occur before licking is exhibited. Source: Modified from Champagne et al., 2004. 597

18. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 18 FIGURE 51.17 Percentage of ewes that selectively interacted with their lamb after 2, 4, or 8 h of inactivation of the cortical (Co), medial (Me), or basolateral (Bl) amygdala with lidocaine beginning at parturition. Inactivation of the cortical or medial nuclei, but not the basolateral nucleus, disrupted selectivity for the lamb. Source: Modified from Keller et al., 2004. 635

19. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 19 FIGURE 51.18 Number (Mean ± SEM) of BrdU-immunoreactive cells in the granule cell layer of the dentate gyrus of female rats measured 21 days after BrdU injection. Primiparous rats were injected with BrdU on postpartum day 1 and had fewer new cells surviving 21 days later compared to nulliparous control females. However, maternally sensitized nulliparous females had more new cells surviving 21 days after the beginning of pup exposure compared to controls. Groups did not differ in BrdU-immunoreactive cells in the hilus of the dentate gyrus. a = significantly different from nulliparous control females; b = significantly different from all other groups. Source: Modified from Pawluski and Galea, 2007. 678

20. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 20 FIGURE 51.19 Hypothetical neural model for the stimulation of active maternal behaviors. The hormones of pregnancy and sensory cues of offspring suppress inhibitory input from the MeA–DH/ AHA–VMN to the mPOA–BSTv while simultaneously stimulating mPOA–BSTv output to the VTA. This elicits dopamine release in the NA, PFC, and BLA. DA release in the NA inhibits VP output, thereby promoting the active components of maternal behavior. The NA, VP, PFC, and BLA can modulate this pathway by their connections to the MPOA–vBST or NA. AHA: anterior hypothalamic area; BLA: basolateral amygdala; BSTv: ventral bed nucleus of the stria terminalis; DH: dorsal hypothalamus; DA: dopamine; MeA: medial amygdala; mPOA: medial preoptic area; NA: nucleus accumbens; PFC: prefrontal cortex; VP: ventral pallidum; VTA: ventral tegmental area. Lines ending in arrows: excitatory input; lines ending in vertical bars: inhibitory input; lines ending in circles: DAergic signaling. Source: Modified from Olazabal et al., 2013. 750

21. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 21 FIGURE 51.20 Sites of the maternal brain where fMRI activity was higher (indicated by red) in mothers who delivered vaginally compared to via Caesarean section while listening to their own infant crying. This figure is reproduced in color in the color plate section. Source: Modified from Swain et al., 2008. 98

22. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition 22 FIGURE 51.21 Sites in the parental brain where mothers (left) or fathers (right) showed greater fMRI activity in response to their own infant video compared to viewing an unfamiliar infant. This figure is reproduced in color in the color plate section. Mothers showed greater activity in the right amygdala and temporal, occipital, and parietal cortices compared to fathers, while fathers had greater activity in the dorsal prefrontal cortex (dPFC). Source: Modified from Atzil et al., 2012. 711