Neuroscience of Affiliation and Social Bonding

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Contents 1 Definitions and Overview 1.1 Terms 1.2 The birth of a field 1.3 A primer on Oxytocin and Vasopressin 2 Often-Cited or New Studies with Accompanying Summaries 2.1 Neuropeptides and social recognition 2.2 Neuropeptides and parental attachments 2.3 Neuropeptides and bonding to mates 2.4 Neuropeptides and non-sexual prosocial behavior 3 Related Sites and Writings 4 References

[edit] Definitions and Overview

[edit] Terms

Neuropeptide: a peptide that acts in the brain. Peptides consist of amino-acids, and can be thought of as very small proteins (proteins consist of one or more long chains of amino acids). Neuropeptides are often released together with neurotransmitters in the brain and act as modulators of neuron function.

[edit] The birth of a field

Until recently, social bonding and affiliative behavior have been best understood from evolutionary and behavioral perspectives -- i.e.: why does sociality evolve, and under what circumstances does social bonding occur? With the growth of molecular biological techniques, in the past two decades scientists have begun to understand the molecular substrates of social behavior. This work has largely focused on the role of two peptide hormones that also act in the brain: oxytocin (OT) and vasopressin (VP). This section gives an introduction to these two neuropeptides. The "often-cited studies" section below explains how OT and VP contribute to social recognition, parental bonding, sexual bonding, and non-sexual affiliation.

[edit] A primer on Oxytocin and Vasopressin

Across the animal kingdom, neuropeptides mediate social and sexual behaviors from egg-laying to affiliation. Neuropeptides in particular may be well suited to affect behavior: they are expressed in discrete regions of the brain, they typically function as long-acting neuromodulators, and both their release and their reception are subject to substantial plasticity based on environmental cues. In particular, a family of related 9-amino-acid peptides including vasopressin, vasotocin, isotocin, mesotocin, and oxytocin affects gender-specific social behaviors in vertebrates (Insel and Young, 2001).

In mammals, the peptides oxytocin (OT) and ariginine vasopressin (AVP or VP) are synthesized in two nuclei of the hypothalamus (the PVN and SON) and are released into the brain, and into the bloodstream (via the posterior pituitary). When circulating in the blood stream, OT plays an important role in muscle contraction, especially during lactation, uterine contraction, and ejaculation (Gimpl and Fahrenholz, 2001). Vasopressin (also known as antidiuretic hormone) is best known for its effects on water balance. AVP binds to receptors in the distal tubule of the kidney where it increases water reabsorption across the epithelium (Campbell and Reece, 2002). While the evidence that peripheral OT and AVP can cross the blood-brain barrier to re-enter the brain is minimal (but see Cushing and Carter, 2000), these peptides are also released centrally in the brain, mostly from parvocellular cells in the PVN (Gimpl and Fahrenholz, 2001). OT binds to the oxytocin receptor (OTR), and AVP binds to the receptors V1a, V1b, and V2 in the brain; of these, only V1a is known to moderate behavioral effects of AVP.

Since the initial discoveries of behavioral influences of OT and AVP, these neuropeptides have been implicated in a wide range of phenomena, including individual recognition, affiliative behavior (reviewed in Insel and Fernald 2004), and learning (Tomizawa et al. 2003).

[edit] Often-Cited or New Studies with Accompanying Summaries

[edit] Neuropeptides and social recognition

Both OT and AVP play important functional roles in the formation of social memories. In tests of social investigation, both male and female OT knockout mice act as complete social amnesiacs after repeated exposures to the same individual (Ferguson et al., 2000). V1a knockout males are similarly impaired, even though animals remain capable of olfactory discrimination and learning (Bielsky et al., 2004). OT’s role in recognition is dependent on steroid hormones. Circulating estrogens enhance OT production in the PVN of the hypothalamus via the estrogen receptor (ER) ER-β, and increase OTR expression in the medial amygdala via ER- α. Knockouts of either estrogen receptor cause deficits similar to those observed in the OT knockout, and more specific manipulations, including targeted infusions of estrogen or ER blockers, vector-based gene delivery, and antisense DNA mediated selective knockouts support this model (Choleris et al., 2004).

[edit] Neuropeptides and parental attachments

Research in a variety of species has shown that OT is an important trigger for maternal behavior. Intracerebroventricular (icv) infusion of OTR antagonists in rats can prevent maternal behaviors entirely, and similar treatments cause a reduction in maternal behaviors in sheep. Conversely, icv administration of OT causes sheep to accept a foreign lamb within 30 seconds of infusion, and even improves maternal behavior (by reducing infanticide) in mice, who do not require OT to be maternal (reviewed in Numan and Insel, 2003).

[Paternal behavior]

[edit] Neuropeptides and bonding to mates

The discovery that oxytocin is important for maternal affiliation led to a second line of research focusing on the pair-bond formed between socially monogamous prairie voles (Microtus ochrogaster). Experimental manipulations of OT have profound effects on behavior in social choice tests in this species: blockade of the OTR decreases time spent next to a familiar animal, and infusion of OT into the cerebrospinal fluid of the brain (or mating) hastens pair-bonding (Cho et al. 1999). In contrast, manipulations of OT in a non-monogamous vole species (Microtus montanus) have little effect on time spent with familiar animals (Insel and Young, 2001).

Monogamous male prairie voles and pine voles also have a pattern of OT and AVP receptor expression that is distinctly different from that of non-monogamous montane voles and meadow voles, with high concentrations of OTR receptors in the nucleus accumbens, and high concentrations of V1a receptors in the ventral pallidum (Young 1999; Young et al. 2001; Lim et al., 2004b). Targeted infusions of OT or an OT antagonist in the NAcc are sufficient to induce or prevent pair-bond formation in females (Young et al., 2001), and infusions of AVP or a V1a antagonist have corresponding effects when infused into the ventral pallidum of male prarie voles (Lim et al., 2004c,d).

Similar contrasts in V1a receptor distributions are found between monogamous and promiscuous mice (Peromyscus californicus and P. leucopus), and to a lesser extent in monkeys (marmosets relative to rhesus monkeys) (Young, 1999). These convergent, parallel differences in receptor expression between related monogamous and non-monogamous species strongly suggest that this correlation underlies differences in behavioral responses to recognition of familiar animals. Indeed, while the genes for AVP and the V1a receptor are relatively conserved across diverse mammalian taxa, natural variations exist in the promoter region for the V1a receptor. These differences underlie at least some of the differences in expression patterns between species, and point towards a potential mechanism for the repeated evolution of monogamous social behavior (Hammock and Young, 2002). Compelling evidence of the causal nature of the relationship between receptor distribution and affiliative behavior comes from the manipulation of endogenous expression of receptors. Following transfection of the gene for prairie vole V1a receptors (including the upstream regulatory region) into the ventral forebrain of male meadow voles, these formerly polygamous voles were actually induced to show partner preference (Lim et al. 2004a). Similarly, expression of the prairie vole V1a gene and upstream region in mice led to prairie vole-like expression patterns and an increase in partner preference.

[edit] Neuropeptides and non-sexual prosocial behavior

OT and AVP have been shown to underlie two biologically important types of social attachment, namely parental behavior and mate affiliation. Less is known about the role of these neuropeptides in non-sexual group behavior (Tang-Martinez, 2003). A few studies in birds and rodents suggest that these peptides do play a role.

[Goodson bird study] [Beery tuco study] [Kosfield human study] [autism therapy?]

[edit] Related Sites and Writings

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[edit] References

• Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ. (2004) Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology 29:483-93

• Campbell, Reece. (2002) Biology. Benjamin Cummings, San Francisco (pages 887 and 900)

• Cho MM, DeVries AC, Williams JR, Carter CS. (1999) The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). Behav Neurosci 113:1071-9

• Choleris E, Kavaliers M, Pfaff DW. (2004) Functional genomics of social recognition. J Neuroendocrinol 16:383-9

• Cushing BS, Carter CS. (2000) Peripheral pulses of oxytocin increase partner preferences in female, but not male, prairie voles. Horm Behav 37:49-56

• de Wied D, Diamant M, Fodor M. (1993) Central nervous system effects of the neurohypophyseal hormones and related peptides. Front Neuroendocrinol 14:251-302

• Dulac C, Torello AT. (2003) Molecular detection of pheromone signals in mammals: from genes to behaviour. Nat Rev Neurosci 4:551-62

• Ferguson JN, Young LJ, Hearn EF, Matzuk MM, Insel TR, Winslow JT. (2000) Social amnesia in mice lacking the oxytocin gene. Nat Genet 25:284-8

• Gimpl G, Fahrenholz F. (2001) The oxytocin receptor system: structure, function, and regulation. Physiol Rev 81:629-83

• Hammock EA, Young LJ. (2002) Variation in the vasopressin V1a receptor promoter and expression: implications for inter- and intraspecific variation in social behaviour. Eur J Neurosci 16:399-402

• Insel TR, Young LJ. (2000) Neuropeptides and the evolution of social behavior. Curr Opin Neurobiol 10:784-9

• Insel TR, Young LJ. (2001) The neurobiology of attachment. Nat Rev Neurosci 2:129-36

• Insel TR, Fernald RD. (2004) How the brain processes social information: searching for the social brain. Annu Rev Neurosci 27:697-722

• Keverne EB, Curley JP. (2004) Vasopressin, oxytocin and social behaviour. Curr Opin Neurobiol 14:777-83

• Lim MM, Wang Z, Olazábal DE, Ren X, Terwilliger EF, Young LJ. (2004a) Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 429:754-7

• Lim MM, Murphy AZ, Young LJ. (2004b) Ventral striatopallidal oxytocin and vasopressin V1a receptors in the monogamous prairie vole (Microtus ochrogaster). J Comp Neurol 468:555-70

• Lim, MM, and LJ Young. (2004c) "Vasopressin-dependent neural circuits underlying pair bond formation in the monogamous prairie vole." Neuroscience. 125: 35-45.

• Lim, MM, EA Hammock, and LJ Young. (2004d) "The role of vasopressin in the genetic and neural regulation of monogamy." J Neuroendocrinol. 16: 325-332.

• Ludwig. (1998) "Dendritic Release of Vasopressin and Oxytocin." J Neuroendocrinol. 10 (1998): 881-881.

• Numan M, Insel TR. (2003) The neurobiology of parental behavior. Springer, New York

• Phelps SM, Young LJ. (2003) Extraordinary diversity in vasopressin (V1a) receptor distributions among wild prairie voles (Microtus ochrogaster): patterns of variation and covariation. J Comp Neurol 466:564-76

• Tang-Martinez, Z. (2003) “Emerging themes and future challenges: forgotten rodents, neglected questions.” J Mammal. 84:1212–1227.

• Tomizawa K, Iga N, Lu YF, Moriwaki A, Matsushita M, Li ST, Miyamoto O, Itano T, Matsui H. (2003) Oxytocin improves long-lasting spatial memory during motherhood through MAP kinase cascade. Nat Neurosci 6:384-90

• Wang Z, Young LJ, Liu Y, Insel TR. (1997) Species differences in vasopressin receptor binding are evident early in development: comparative anatomic studies in prairie and montane voles. J Comp Neurol 378:535-46

• Winslow JT, Insel TR. (2004) Neuroendocrine basis of social recognition. Curr Opin Neurobiol 14:248-53

• Young LJ. (1999) Frank A. Beach Award. Oxytocin and vasopressin receptors and species-typical social behaviors. Horm Behav 36:212-21

• Young LJ, Lim MM, Gingrich B, Insel TR. (2001) Cellular mechanisms of social attachment. Horm Behav 40:133-8