Abstract
The arginine vasopressin 1b receptor (Avpr1b) plays an important role in social behaviors including aggression, social learning and memory. Genetic removal of Avpr1b from mouse models results in deficits in aggression and short-term social recognition in adults. Avpr1b gene expression is highly enriched in the pyramidal neurons of the hippocampal cornu ammonis 2 (CA2) region. Activity of the hippocampal CA2 has been shown to be required for normal short-term social recognition and aggressive behaviors. Vasopressin acts to enhance synaptic responses of CA2 neurons through a NMDA-receptor dependent mechanism. Genetic removal of the obligatory subunit of the NMDA receptor (Grin1) within distinct hippocampal regions impairs non-social learning and memory. However, the question of a direct role for NMDA receptor activity in Avpr1b neurons to modulate social behavior remains unclear. To answer this question, we first created a novel transgenic mouse line with Cre recombinase knocked into the Avpr1b coding region to genetically target Avpr1b neurons. We confirmed this line has dense Cre expression throughout the dorsal and ventral CA2 regions of the hippocampus, along with scattered expression within the caudate-putamen and olfactory bulb (OB). Conditional removal of the NMDA receptor was achieved by crossing our line to an available floxed Grin1 line. The resulting mice were measured on a battery of social and memory behavioral tests. Surprisingly, we did not observe any differences between Avpr1b-Grin1 knockout mice and their wildtype siblings. We conclude that mice without typical NMDA receptor function in Avpr1b neurons can develop normal aggression as well as short-term social and object memory performance.
Highlights
The neuromodulatory actions of arginine-vasopressin (Avp) are required for the typical expression of social and stressrelated behaviors in clinical populations and preclinical models (Caldwell et al, 2017; Williams Avram and Cymerblit-Sabba, 2017)
To confirm that the Avpr1b gene expression is restricted to the pyramidal cells of the cornu ammonis 2 (CA2), double in situ hybridization was performed with the dorsal CA2 marker adhesion molecule with Ig-Like domain 2 (Amigo2) (Figure 1D)
Avpr1b gene expression was observed in many fewer cells, while Amigo2 was observed in the most ventral regions of the CA1 and in posterior CA3 cells (Figure 1G)
Summary
The neuromodulatory actions of arginine-vasopressin (Avp) are required for the typical expression of social and stressrelated behaviors in clinical populations and preclinical models (Caldwell et al, 2017; Williams Avram and Cymerblit-Sabba, 2017). Recent data indicate that variation in Avpr1b signaling may have maladaptive impacts on human social behavior. Life-long disruption of Avpr1b signaling through genetic removal in knockout (KO) mice results in altered social aggression and social memory performance (Wersinger et al, 2002), while leaving spatial and object memory performance and olfactory discrimination intact, indicating a special role in the social aspect of memory (Wersinger et al, 2002, 2004, 2007; Caldwell et al, 2008). Decreases in social aggression occurred in both sexes, suggesting a conserved signaling mechanism for males and females, unlike many of Avp’s actions through Avpr1a (Terranova et al, 2016; Williams Avram and Cymerblit-Sabba, 2017)
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