title: Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2.
abstract: The vasopressin 1b receptor (Avpr1b) is critical for social memory and social aggression in rodents, yet little is known about its specific roles in these behaviors. Some clues to Avpr1b function can be gained from its profile of expression in the brain, which is largely limited to the pyramidal neurons of the CA2 region of the hippocampus, and from experiments showing that inactivation of the gene or antagonism of the receptor leads to a reduction in social aggression. Here we show that partial replacement of the Avpr1b through lentiviral delivery into the dorsal CA2 region restored the probability of socially motivated attack behavior in total Avpr1b knockout mice, without altering anxiety-like behaviors. To further explore the role of the Avpr1b in this hippocampal region, we examined the effects of Avpr1b agonists on pyramidal neurons in mouse and rat hippocampal slices. We found that selective Avpr1b agonists induced significant potentiation of excitatory synaptic responses in CA2, but not in CA1 or in slices from Avpr1b knockout mice. In a way that is mechanistically very similar to synaptic potentiation induced by oxytocin, Avpr1b agonist-induced potentiation of CA2 synapses relies on NMDA (N-methyl-D-aspartic acid) receptor activation, calcium and calcium/calmodulin-dependent protein kinase II activity, but not on cAMP-dependent protein kinase activity or presynaptic mechanisms. Our data indicate that the hippocampal CA2 is important for attacking in response to a male intruder and that the Avpr1b, likely through its role in regulating CA2 synaptic plasticity, is a necessary mediator.
authors.affiliation: Section on Neural Gene Expression, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Pagani
authors.affiliation: Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Section on Neural Gene Expression, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Section on Neural Gene Expression, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S K Williams
authors.initials: SK
authors.lastname: Avram
authors.affiliation: Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Caruana
authors.affiliation: Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Dudek
authors.affiliation: Section on Neural Gene Expression, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Young
mesh_terms: D000374:Aggression / Q000502:physiology*; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology; D056651:CA2 Region, Hippocampal / Q000166:cytology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002452:Cell Count; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D016086:Lentivirus / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics*; D014161:Transduction, Genetic
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; C576074:OXTR protein, mouse; D016194:Receptors, N-Methyl-D-Aspartate; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2