Zuoxin Wang

Distinguished Research Professor

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Contact Information

B343
Neuroscience
Faculty

Education

University of Massachusetts at Amherst, 1991

Research Interests

Neurobiology of social Attachment, environmental and hormonal regulation of adult neurogenesis, Social and drug reward interactions and underlying mechanisms.

Current Research

Neurobiology of Social Attachment

The major emphasis of our research has been the neurobiology of social attachment in mammals. Sexual attraction and the selective social attachments that often follow are two of the most powerful driving forces of human behavior. There is little doubt that the ability to form intense social attachments - or pair bonds - with a mate has a biological architecture with definable molecular and neural mechanisms. Our laboratory uses the monogamous prairie vole (Microtus ochrogaster) as a model system to study the neuronal and hormonal mechanisms underlying social attachment because this rodent species exhibits high levels of mating-induced pair bonding. Our earlier work, along with the work of others, demonstrated that the neuropeptides vasopressin and oxytocin in particular brain areas play important roles in pair bond formation of male and female prairie voles. Our recent work has been focused on dopamine, a neurochemical that is released during both natural and drug rewards and that plays an important role in learning and memory. We have demonstrated that dopamine is released during mating in the nucleus accumbens (NAcc), an area which contains dopamine terminals and different types of dopamine receptors in voles. We have shown that, in the NAcc, dopamine differentially mediates formation and maintenance of pair bonding behavior in a receptor-specific manner. Further, we have demonstrated that dopamine and oxytocin interact in NAcc in the regulation of pair bonding. Our current efforts are focused on the examination of intracellular mechanisms underlying receptor-specific dopamine effects and dopamine interactions with oxytocin/vasopressin in the regulation of pair bonding.

Environmental and Hormonal Regulation of Adult Neurogenesis

Although recent studies have amply demonstrated that neurogenesis occurs continuously throughout life in certain brain areas of adult vertebrates, including rodents, non-human primates, and humans, the factors that influence and are functionally important for this process remain largely unexplored. Because manipulations of the social environment have profound effects on physiology and behaviors of the prairie vole, we have used this model system to study the effects of environmental and hormonal manipulation on adult neurogenesis. We have demonstrated that in female prairie voles, mating and experience with a male facilitate, whereas social isolation inhibits, neurogenesis in selected brain areas. We have also found that the gonadal steroid hormone, estrogen, differently regulates neurogenesis in selected brain areas of females between monogamous and non-monogamous voles. Further, in male voles, we have found that gonadal steroid hormones, including testosterone and estrogen, may act on estrogen-receptor mediated mechanisms in the regulation of locally proliferated cells in the amygdala - a brain area implicated in social behaviors. Our current efforts are focused on the interactions between gonadal steroid hormones and other neurochemicals in the regulation of adult neurogenesis, and on the functional significance of new neurons in social behaviors.

Social and Drug Reward Interactions and Underlying Mechanisms

Our newest line of research is to develop the prairie vole model for the study of social and drug reward interactions and their underlying mechanisms. As noted above, we have demonstrated that NAcc dopamine regulates prairie vole pair bonding behavior. Interestingly, dopamine regulation of pair bonding appears to be very similar to dopamine regulation of drug seeking behavior. Because pair bonding and drug reward are regulated by very similar neural mechanisms, and because both result in enduring changes in behavior, we hypothesized that addiction to drugs of abuse and pair bonding may act on the same brain-reward circuitry, and that the two may interact with each other. The prairie vole is the perfect animal model to test this hypothesis. Our recent data have shown that prairie voles display amphetamine-induced conditioned place preferences (CPP), suggesting that amphetamine is rewarding in voles as in other species of rodents. Our current efforts are focused on examining changes in brain-reward dopamine circuitry after amphetamine treatment, and on comparing such changes with those induced by pair bonding.

Lab Description

Neuronal and hormonal bases of social behavior, sexual differentiation of brain and behavior, and neural development and plasticity.

Gobrogge KL, Jia X, Liu Y, and Wang ZX (2017) Neurochemical mediation of affiliation and aggression associated with pair bonding. Biol Psychiatry, 81:231-242.

Smith AS, Tabbaa M, Lei K, Eastham P, Butler MJ, Linton L, Altshuler R, Liu Y, and Wang ZX (2016) Local oxytocin tempers anxiety by activating GABAA receptor in the hypothalamic paraventricular nucleus. Psychoneuroendocrinology, 63:50-58.

Lieberwirth C and Wang ZX (2016) The neurobiology of pair bond formation, bond disruption, and social buffering. Curr Opin Neurobiol, 40:8-13.

Gobrogge KL and Wang ZX (2016) The ties that bond: neurochemistry of attachment in voles. Curr Opin Neurobiol, 38:80-88.

Fukushiro-Lopes DF, Olivera A, Liu Y, and Wang ZX (2015) Neonatal exposure to amphetamine alters social affiliation and central dopamine activity in adult male prairie voles. Neuroscience, 307:109-116.

Young, KA, Liu, Y, Gobrogge, KL, Wang, H, Wang ZX (2014) Oxytocin reverses amphetamine-induced deficits in social bonding: evidence for an interaction with nucleus accumbens dopamine. J. Neurosci., 34:8499-8506.

Smith AS and Wang ZX (2014) Hypothalamic oxytocin mediates social buffering of the stress response. Biological Psychiatry, 76:281-288.

Liu Y, Lieberwirth C, Jia X, Curtis JT, Meredith M, and Wang ZX (2014) Chemosensory cues affect amygdaloid neurogenesis and alter behaviors in the socially monogamous prairie vole. Eur. J. Neurosci., 39:1632-1641.

Wang H, Duclot F, Liu Y, Wang ZX, and Kabbaj M (2013) Histone deacetylase inhibitors facilitate partner preference formation in female prairie voles. Nature Neurosci., 16:919-924.

Lieberwirth C, Wang Y, Jia X, Liu Y, and Wang ZX (2013) Fatherhood reduces the survival of adult-generated cells and affects various types of behaviors. Eur J. Neurosci., 38:3345-3355.

Young KA, Gobrogge KL, and Wang ZX (2011) The role of mesocorticolimbic dopamine in regulating interactions between drugs of abuse and social behavior. Neurosci. Biobehav. Rev., 35:498-515.

Young KA, Gobrogge KL, Liu Y, and Wang ZX (2011) The neurobiology of pair bonding: insights from a socially monogamous rodent. Frontiers Neuroendocrin., 32:53-69.

Liu Y, Young KA, Curtis TC, Aragona B, and Wang ZX (2011) Social bonding decreases the rewarding properties of amphetamine through a dopamine D1 receptor mediated mechanism. J. Neurosci., 31: 7960-7966.

Liu Y, Aragona BJ, Young KA, Dietz DM, Kabbaj M, Mazei-Robison M, Nestler EJ, and Wang ZX (2010) Nucleus accumbens dopamine mediates amphetamine-induced impairment of social bonding in a monogamous rodent species. Proc. Natl. Acad. Sci., USA, 107: 1217-1222.

Gobrogge K, Liu Y, Young LJ, and Wang ZX (2009) Anterior hypothalamic vasopressin regulates pair bonding- and drug-induced aggression in a monogamous rodent. Proc. Natl. Acad. Sci., USA, 106:19144-19149.

Aragona BJ and Wang ZX (2007) Opposing regulation of pair bond formation by cAMP signaling within the nucleus accumbens shell. J. Neurosci., 27:13352-13356.

Aragona BJ, Liu Y, Yu J, Curtis TJ, Detwiler J, Insel TR and Wang ZX (2006) Nucleus accumbens dopamine differentially mediates formation and maintenance of monogamous pair bonds. Nature Neurosci., 9:133-139.

Young LJ and Wang ZX (2004) The neurobiology of pair bonding. Nature Neurosci., 7:1048-1054.

Lim MM, Wang ZX, Olazabal DE, Ren X, Terwilliger EF, and Young LJ (2004) Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature, 429:754-757.

Aragona BJ, Liu Y, Curtis, TJ, Stephan FK, and Wang ZX (2003) A critical role for nucleus accumbens dopamine in partner-preference formation in male prairie voles. J. Neurosci., 23:3483-3490.


Undergraduate Research

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