Viral vector‐mediated gene transfer of the vole V1a vasopressin receptor in the rat septum: improved social discrimination and active social behaviour

Abstract

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.

The neurobiology of social attachment: A comparative approach to behavioral, neuroanatomical, and neurochemical studies

“…This idea is supported by data from several transgenic studies (Pitkow et al, 2001;Landgraf et al, 2003;Lim et al, 2004b). For example, transgenic mice that received the prairie vole V1aR gene had a distribution pattern of V1aRs in the brain similar to that of prairie voles but different from that of nontransgenic mice.…”

Profound Impairment in Social Recognition and Reduction in Anxiety-Like Behavior in Vasopressin V1a Receptor Knockout Mice

“…Normal social recognition lasts between 30 and 60 min and the facilitating effects of AVP administration appear to improve the consolidation of the social memory given that administration is effective if given after the initial encounter Le Moal et al, 1987). Increased expression of the V1aR in the lateral septum, using viral vector gene transfer, resulted in a similar facilitation of social recognition (Landgraf et al, 2003). OT has also been shown to be critical to social recognition, and animals lacking OT (OTKO) have severely impaired social memory (Ferguson et al, 2000); however, the effects of OT on social recognition differ from the effects of AVP.…”

Neuropeptide binding reflects convergent and divergent evolution in species-typical group sizes

“…Social recognition is severely impaired in V 1a receptor knockout mice (Bielsky et al, 2004) and re-expression of V 1a receptors in the LS by viral vector completely restores social memory (Bielsky et al, 2005). Similarly, viral vector-mediated over-expression of septal V 1a receptors improves social recognition in rats (Landgraf et al, 2003), and also facilitates active social interactions. We hypothesize that V 1a -like receptors perform similar functions in birds, given that gregarious estrildids exhibit significantly higher densities of V 1a -like receptors in the septal nuclei than do less social, territorial species.…”