Matrix metalloproteinases and diseases of the CNS

European Journal of Neuroscience, 2003

This study explores the effects of enhancing vasopressin V1a receptor expression in the septum using viral vector-mediated gene transfer on social discrimination and social interactions. Bilateral infusion of an adeno-associated viral vector containing the prairie vole V1a receptor gene (V1aR-AAV) regulated by a neuron-specific enolase promoter resulted in a stable increase in V1a receptor binding density in the rat septum without affecting oxytocin receptor density. Control animals were infused with a vector expressing the lacZ gene. In a social discrimination paradigm, only V1aR-AAV-treated animals succeeded in discriminating a previously encountered from a novel juvenile after an interexposure interval (IEI) of more than 2 h, demonstrating the functional incorporation of the vole V1a receptor in the rat septal circuits underlying short-term memory processes. Microdialysis administration of synthetic vasopressin during the first juvenile exposure, used to mimic intraseptal release patterns of the neuropeptide, produced similar prolongations in recognition (up to an IEI of 24 h) in both V1aR-AAV and control animals. Septal microdialysis administration of a selective V1a, but not oxytocin, receptor antagonist in both groups prevented discrimination even after an IEI of as short as 0.5 h, confirming the specificity of the vole V1a receptor involvement in social discrimination abilities. In addition, active social interactions were found to be increased among V1aR-AAV rats compared to controls. Viral vector-mediated gene transfer provides a valuable tool for studies on the role of localized gene expression on behavioural parameters.

Nature, 1999

Arginine vasopressin influences male reproductive and social behaviours in several vertebrate taxa through its actions at the V1a receptor in the brain. The neuroanatomical distribution of vasopressin V1a receptors varies greatly between species with different forms of social organization. Here we show that centrally administered arginine vasopressin increases affiliative behaviour in the highly social, monogamous prairie vole, but not in the relatively asocial, promiscuous montane vole. Molecular analyses indicate that gene duplication and/or changes in promoter structure of the prairie vole receptor gene may contribute to the species differences in vasopressin-receptor expression. We further show that mice that are transgenic for the prairie vole receptor gene have a neuroanatomical pattern of receptor binding that is similar to that of the prairie vole, and exhibit increased affiliative behaviour after injection with arginine vasopressin. These data indicate that the pattern of V...

Journal of Zoology, 2016

Social monogamy is a mating strategy rarely employed by mammalian species. Laboratory studies in socially monogamous prairie voles (Microtus ochrogaster) demonstrate that oxytocin and vasopressin act within the mesolimbic dopamine pathway to facilitate pair-bond formation. Species differences in oxytocin receptor (OTR) and vasopressin 1a receptor (V1aR) distribution in this pathway are associated with species differences in mating strategy. Here we characterize the neuroanatomical distribution of OTR and V1aR binding sites in naturally occurring populations of Taiwan voles (M. kikuchii), which purportedly display social monogamy. Live trapping was conducted at two sites in 2009-2010 and receptor autoradiography for OTR and V1aR was performed on brains from 24 animals. OTR binding in two brain regions where OTR signaling regulates pair-bonding were directly compared with that of prairie voles. Our results show that like prairie voles, Taiwan voles exhibit OTR in the prefrontal cortex, insular cortex, claustrum, nucleus accumbens, caudate-putamen, dorsal lateral septal nucleus, central amygdala, and ventromedial hypothalamus. Unlike prairie voles, Taiwan voles exhibit OTR binding in the CA3 pathway of the hippocampus, as well as the indusium griseum, which has only previously been documented in tuco-tucos (Ctenomys haigi, C. sociabilis), Syrian hamsters (Mesocricetus auratus) and naked mole-rats (Heterocephalus glaber). V1aR binding was present in the ventral pallidum, lateral septum, nucleus basalis, bed nucleus of the stria terminalis, hippocampus, medial amygdala, and anterior, ventromedial and dorsomedial hypothalamus. Marked individual differences in V1aR binding were noted in the cingulate cortex and several thalamic nuclei, remarkably similar to prairie voles. While pharmacological studies are needed to determine whether oxytocin and

Brain Research, 2005

Reward mechanisms are involved in pair bond formation in monogamous prairie voles. Given the potential role of CART (cocaine-and amphetamine-regulated transcript) in reward, and its possible role as a third neurohypophysial hormone, we examined the brain distribution of CART mRNA and peptide in monogamous prairie voles compared to congener promiscuous meadow voles. Large species differences in CART mRNA distribution were apparent in the nucleus accumbens, bed nucleus of the stria terminalis, hippocampus, and cortex. CART peptide distribution largely mirrored, but did not exactly match, CART mRNA distribution. Dramatic species differences also existed in CART peptide distribution, including the medial preoptic area, nucleus accumbens, central amygdala, lateral septum, and cortex. In contrast, several brain regions were highly conserved between prairie and meadow voles, including many subnuclei examined within the hypothalamus and olfactory tubercle. Taken together, these data suggest a potential role for CART in the regulation of pair bond formation between monogamous mates and suggest potential brain regions involved in its neural circuitry. Our findings also point to novel avenues of investigation regarding the brain mechanisms for the evolution of diverse social organization. D

Current Opinion in Neurobiology, 2016

In socially monogamous prairie voles (Microtus ochrogaster), mating induces three primary types of behavior; namely, partner preference, selective aggression toward conspecific strangers, and bi-parental care, making this rodent an ideal model system to study sociality and underlying neurochemical mechanisms associated with monogamous mating strategies. Here, we highlight species differences in neurochemical receptor distributions associated with mating experience leading to the establishment of stable pair-bonds. Specifically, we illustrate the role of nucleus accumbens dopamine in programming the formation and maintenance of monogamous bonds and describe the role of anterior hypothalamic vasopressin in the regulation of selective aggression. We conclude by discussing recent molecular work in voles and emphasize the importance of this rodent for future research in the behavioral neurobiology field.

Neuroscience Letters, 2003

The expression of c-fos, a marker of neuronal activation, was examined in the gracile nucleus (GN) and nucleus of the solitary tract (NTS) after social interactions, including mating, between male and female prairie voles. In GN, mating, but not non-sexual interactions, induced similar significant increases in c-fos immunoreactivity in both males and females. The increased immunoreactivity was concentrated in medial and dorsal GN suggesting that expression was driven by stimulation of reproductive organs. In contrast, in NTS, mating-induced increases in c-fos expression occurred only in males. These results suggest that both GN and NTS comprise different functional components of mating circuitry and may contribute to pair bonding in monogamous voles. q

Neuroscience Letters, 2006

Comparisons between monogamous and promiscuous vole species have proven useful in examining neurobiological mechanisms underlying social attachment. Reward processing is important for social attachment, and the medial prefrontal cortex (mPFC) exerts a direct influence on reward pathways. Dopamine (DA), oxytocin (OT), and arginine vasopressin (AVP) all have been implicated in the regulation of social attachment in monogamous voles. Therefore, we used radiolabeled ligands to examine dopamine D 1 -and D 2 -like, OT, and AVP V 1a receptor binding densities in the mPFC of monogamous and promiscuous voles. Species differences were found; monogamous voles had higher densities of D 2 -like and OT receptor binding and lower densities of D 1 -like and V 1a receptor binding than did promiscuous voles. Sex differences also were found; females had higher densities of OT receptor binding but lower densities of V 1a receptor binding than did males in both species. Further, the laminar distribution of receptor binding indicates the possibility of an interaction between DA and OT systems in the mPFC in the regulation of social attachment. Differences in D 1 -and D 2 -like receptor binding between species are discussed in terms of how they might modulate cortical activity and subsequent DA release in the nucleus accumbens (NAcc).

Behavioral Neuroscience, 1995

Vasopressin-immunoreactive (AVP-ir) cells in the bed nucleus of the stria terminalis (BST) and medial amygdaloid nucleus (MA) and their AVP-ir projections to the lateral septum were studied in monogamous prairie voles (Microtus ochrogaster) and promiscuous meadow voles (M. pennsylvanicus). A sexually dimorphic AVP-ir pathway was found in both species; males had more AVP-ir cells in the BST and MA, as well as denser AVP-ir fibers in the lateral septum, than did females. A significant species difference was also found. Overall, meadow voles had more AVP-ir cells in the BST and MA than did prairie voles. Male prairie voles, however, had a higher density of AVP-ir fibers in the lateral septum than male meadow voles. The species difference in the sexually dimorphic AVP-ir projections in the BST and MA is implicated in the rodents' different life strategy and behavior.

Neuroscience, 2015

Microtine rodents display diverse patterns of social organization and behaviors, and thus provide a useful model for studying the effects of the social environment on physiology and behavior. The current study compared the species differences and the effects of oxytocin (OT) on anxiety-like, social affiliation, and social recognition behaviors in female meadow voles (Microtus pennsylvanicus) and prairie voles (M. ochrogaster). Furthermore, cell proliferation and survival in the brains of adult female meadow and prairie voles were compared. We found that female meadow voles displayed a higher level of anxiety-like behavior but lower levels of social affiliation and social recognition compared to female prairie voles. In addition, meadow voles showed lower levels of cell proliferation (measured by Ki67 staining) and cell survival (measured by BrdU staining) in the ventromedial hypothalamus (VMH) and amygdala (AMY), but not the dentate gyrus of the hippocampus (DG), than prairie voles....