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 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.

The Vasopressin 1b Receptor Antagonist A-988315 Blocks Stress Effects on the Retrieval of Object-Recognition Memory

“…Some evidence further suggests that V1b receptors might have a role in hippocampal neural plasticity (Pagani et al, 2014) and hippocampusdependent memory for temporal order (DeVito et al, 2009). Consistent with the present findings, mice lacking the V1b receptor showed normal recognition of previously explored objects and remembered where they were experienced; however, they displayed a very specific impairment in remembering the hippocampus-dependent temporal order of presentation of those objects (DeVito et al, 2009).…”

“…Moreover, there is some evidence that V1b-receptor activation is involved in regulating aggressive and social behaviors. It has been reported that mice lacking a functional V1b receptor are deficient in sociability and detecting social novelty (Caldwell et al, 2008;Stephenson and Caldwell, 2012;Pagani et al, 2014). It is Figure 4 Effect of pretest administration of A-988315 on stress-induced increases in plasma ACTH and corticosterone levels.…”

Regulator of G Protein Signaling 14

“…80 The Avpr1b receptor is highly restricted in its expression to CA2 pyramidal neurons. 78 Application of specific Avpr1b agonists to rat and mouse brain slices induced synaptic potentiation of excitatory currents selectively in CA2, but not in CA1.…”

Hippocampal CA2 Region: A New Player in Social Dysfunctions

“…Piskorowski et al [37] reported that in the 22q11.2 mouse model (a mouse model for neuropsychiatric disorders, including autism and schizophrenia), the density of parvalbumin-expressing interneurons was decreased specifically in CA2 of adult mice. CA2 pyramidal neurons displayed a more hyperpolarized resting membrane potential, which made them less responsive to input stimulation.…”

“…Recently, the role of a long-neglected subdivision of the hippocampus, CA2, has come to light. An increasing body of evidences suggests that CA2 itself is far more than a passive transition region between CA1 and CA3 but a functional unit [32][33][34][35][36][37][38][39][40].…”