Neural mechanisms of mother-infant bonding and pair bonding: Similarities, differences, and broader implications

Abstract

This article is part of a Special Issue "Parental Care". Mother-infant bonding is a characteristic of virtually all mammals. The maternal neural system may have provided the scaffold upon which other types of social bonds in mammals have been built. For example, most mammals exhibit a polygamous mating system, but monogamy and pair bonding between mating partners occur in ~5% of mammalian species. In mammals, it is plausible that the neural mechanisms that promote mother-infant bonding have been modified by natural selection to establish the capacity to develop a selective bond with a mate during the evolution of monogamous mating strategies. Here we compare the details of the neural mechanisms that promote mother-infant bonding in rats and other mammals with those that underpin pair bond formation in the monogamous prairie vole. Although details remain to be resolved, remarkable similarities and a few differences between the mechanisms underlying these two types of bond formation are revealed. For example, amygdala and nucleus accumbens-ventral pallidum (NA-VP) circuits are involved in both types of bond formation, and dopamine and oxytocin actions within NA appear to promote the synaptic plasticity that allows either infant or mating partner stimuli to persistently activate NA-VP attraction circuits, leading to an enduring social attraction and bonding. Further, although the medial preoptic area is essential for maternal behavior, its role in pair bonding remains to be determined. Our review concludes by examining the broader implications of this comparative analysis, and evidence is provided that the maternal care system may have also provided the basic neural foundation for other types of strong social relationships, beyond pair bonding, in mammals, including humans.

Keywords: Amygdala; Dopamine; Medial preoptic area; Monogamy; Nucleus accumbens; Oxytocin; Social attachment; Vasopressin; Ventral pallidum.

Figure 1

A neural model showing how an hormonally primed medial preoptic area and adjoining ventral bed nucleus of the stria terminalis (MPOA/vBST) might influence maternal motivation by interacting with the mesolimbic dopamine (DA) system. Pregnancy hormones (estradiol = E; prolactin = prol) act on MPOA/vBST, rendering such neurons responsive to oxytocin (OT) (derived from the paraventricular hypothalamic nucleus: PVN) and to multimodal pup stimuli derived from the medial prefrontal cortex (mPFC). The activated MPOA/vBST efferents project to and stimulate ventral tegmental area (VTA) DA input to nucleus accumbens shell (NAs). DA action on NAs depresses the responsiveness of NAs to afferent glutamatergic (glut) inputs from the basomedial and basolateral amygdala (BMA/BLA). These latter regions are shown as relaying pup-related sensory inputs to both NAs and ventral pallidum (VP). Depression of NA responsiveness releases the VP from GABAergic inhibition derived from NAs, which opens a gate that allows VP to fully respond to BMA/BLA inputs. A fully active VP is proposed to be necessary for the occurrence of appetitive maternal responses. Axons ending in an arrow indicate excitation and those ending in a bar indicate inhibition. Modified from Figure 6 in Numan and Stolzenberg (2009) with permission from Elsevier.

Figure 2

Dopamine action on D1 and D2 receptors (A), and oxytocin action on oxytocin receptors (B), in the nucleus accumbens shell (NAs) are involved in the establishment of maternal memory in rats. Primiparous rats are allowed one hour of postpartum experience with their young, after which the pups are removed. Immediately thereafter, various neurochemicals are microinjected into NAs in different groups of rats. Ten days later, the rats are re-exposed to pups and sensitization latencies are measured. As shown in A, blockade of both D1 and D2 receptors in NAs with flupenthixol disrupts maternal memory formation (Parada et al., 2008). As shown in B, injection of an oxytocin receptor antagonist (OTA) into NAs also blocks maternal memory formation (D'Cunha et al., 2011). Other abbreviations: CSF = artificial cerebrospinal fluid. In comparing these findings with the development of pair bonds in prairie voles, as shown in Fig. 5, a crucial similarity is that DA action on D2 receptors and OT action on OT receptors within NA are involved in both types of bond formation. Reproduced from Figure 5.16 in Numan (2015) with permission from Elsevier.

Figure 3

A neural model for maternal memory formation in rats. The model describes how oxytocin (OT) and dopamine (DA) action on the nucleus accumbens shell (NAs), driven in part by medial preoptic area (MPOA) activity during an initial maternal experience, might promote synaptic strengthening (dashed circle) across synapses between the basomedial/basolateral amygdala (BMA/BLA) and the ventral pallidum (VP). This synaptic strengthening is proposed to be important for maternal memory formation. An important underlying assumption of the model is that strong depression of NAs medium spiny neuron (MSN) inhibition of VP allows the VP to be super-excited by BMA/BLA glutamatergic inputs, which then strengthens the BMA/BLA-to-VP synapse. The MPOA is shown as activating DA and OT release into NAs. OT release into NAs is also activated by the vaginocerivcal stimulation (VCS) and suckling stimulation that occurs in parturient rats. The paraventricular hypothalamic nucleus (PVN) is shown as the source of OT input to NAs. DA action on presynaptic D1 receptors depresses BMA/BLA excitation of MSNs. DA action of D2 receptors directly depresses MSNs that project to VP. D2 dopamine receptors may form heteromers with oxytocin receptors (OTR) on MSNs, and OT action at such OTRs appears to act as a neuromodulator, enhancing the inhibitory effects of DA at the associated D2 receptor. These combined effects should result in a profound depression of neural activity between NAs and VP. Axons ending in a bar have inhibitory effects, and those ending in an arrow are excitatory. Other abbreviations: E = estradiol; Prol = prolactin; VTA = ventral tegmental area. Modified from Figure 5.17 in Numan (2015) with permission from Elsevier.

Figure 4

Receptor autoradiograms illustrating species differences in oxytocin receptor (OTR, top row) and vasopressin V1a receptor (V1aR, bottom row) densities in the nucleus accumbens (NA) and ventral palliudm (VP) of monogamous prairie voles (left panels) and nonmonogamous montane voles (right panels). These species differences in distribution of receptors in the NA-VP circuit are thought to mediate species differences in the ability to form pair bonds in voles. While the role of OTR in the NA has been most extensively studied in female bonding, and the role of V1aR in the VP has been most extensively studied in male bonding, there are no sex differences in receptor density in either brain region. Modified from Young and Wang (2004).

Figure 5

A hypothetical neural model of pair bond formation in prairie voles. The model proposes that during a mating bout both ventral tegmental area (VTA) dopamine (DA) input to nucleus accumbens shell (NAs) and paraventricular hypothalamic (PVN) oxytocin (OT) input to the NAs and to the olfactory bulbs and amygdala are stimulated. In addition, olfactory and other stimuli from the mating partner activate amygdala glutamatergic (Glut) input to nucleus accumbens-ventral pallidum circuit (NA-VP) and arginine vasopressin (AVP) input, proposed to arise from the medial amygdala (MeA: Lim & Young, 2004), to VP. The mechanisms of pair bond formation involve a two-step process: an individual recognition stage and a persistent attraction phase. OT action on oxytocin receptors (OTR) at the level of the olfactory bulbs and amygdala is shown as promoting social memory by strengthening synapses in the amygdala (outlined with a dashed circle) that then allow olfactory and other stimuli from the mating partner to strongly activate amygdala input to NA-VP. For the development of a persistent attraction to one's mating partner, DA action on D2 receptors and OT action on OTRs in NA (shown as D2-OTR heteromers) are proposed to depress the activity of NA GABAergic medium spiny neuron (MSN) input to VP, resulting in a disinhibition of VP. The disinhibited VP is now strongly activated by the partner-induced glutamate and AVP input that it receives from the amygdala, and these synapses are strengthened (outlined with a dashed circle). Once mating is completed, and a mate is given a partner preference test, the olfactory and other stimulus characteristics of the partner, but not those of a stranger, are now capable of strongly activating VP over long periods of time, creating an enduring and selective social bond. In fact, stranger-related stimuli activate AVP release into anterior hypothalamus (not shown) leading to aggression and rejection. Mechanisms similar to these may be involved in maternal bonding and selectivity in sheep. Note that although OT typically has excitatory effects in neurons (Terenzi & Ingram, 2005), when it acts at sites composed of D2-OTR heteromers, it functions to potentiate the inhibitory effects of DA at the D2 receptor. In order to simplify the diagram and show its similarities with Fig. 3, the presence of D1 receptors on NA MSNs is not shown although, as indicated in the text, DA action at this site suppresses pair bond formation. Perhaps OT not only suppresses the output of MSNs with D2 receptors, but also those with D1 receptors (see Numan, 2015). Other abbreviations: AOB = accessory olfactory bulb; BLA = basolateral amygdala; BMA = basomedial amygdala; GluR = glutamate receptor; OB = olfactory bulb; V1aR = vasopressin V1a receptor. Modified from Figures 6.2 and 6.3 in Numan (2015) with permission from Elsevier.