NMDA receptor in vasopressin 1b neurons is not required for short-term social memory, object memory or aggression

• Published in: bioRxiv
• Main Authors: Sarah Williams Avram, Jarrett Fastman, Cymerblit-Sabba, Adi, Smith, Adam, Mathew, Vincent, Song, June, Heon-Jin, Lee, Granovetter, Michael, Su Hyun Lee, Cilz, Nick, Stackmann, Michelle, Chaturvedi, Rahul, Young, W Scott
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 13.06.2019
• Subjects: Aggression; Animal models; Caudate-putamen; Coding; Cre recombinase; Gene expression; Glutamic acid receptors (ionotropic); Hippocampus; N-Methyl-D-aspartic acid receptors; Observational learning; Olfactory bulb; Putamen; Pyramidal cells; Short term; Social behavior; Social discrimination learning; Social interactions; Transgenic mice; Vasopressin
• DOI: 10.1101/670893

The 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. 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.