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

Abstract

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.Significance StatementActivity of neurons that express vasopressin 1b receptor are essential for aggressive and social recognition behaviors. We created a novel transgenic mouse to allow selective targeting of vasopressin 1b neurons. Our studies indicate that NMDA receptor expression in vasopressin 1b neurons (including most CA2 neurons) are not required for development of the typical expression of aggression or recognition memory. Thus, CA2 neurons may have a unique way of incorporating novel stimuli into memory that deserves further investigation.

Simultaneous Knockouts of the Oxytocin and Vasopressin 1b Receptors in Hippocampal CA2 Impair Social Memory

“…We validated colocalization of Oxtr and Avpr1b transcripts in the CA2, with Oxtr extending into adjacent CA3 (Fig. 1a), consistent with previous reports 5, 23 . We also confirmed the reduction of Oxtr expression in the CA2 of HE and DKO mice and of Avpr1b expression in the DKO mice (Fig.…”

“…Restricted removal of both receptors from the pyramidal neurons of CA2 allowed us to investigate the functional significance of the cross-talk in this region. Previously, we showed that the life-long absence of Avpr1b resulted in impaired social recognition in both our knockout 6 and knockin 5 lines. We predicted similar, if not greater, impairments with the removal of both Oxtr and Avpr1b.…”

“…All experiments were conducted according to US National Institutes of Health guidelines for animal research and were approved by the National Institute of Mental Health Animal Care and Use Committee. We bred our Avpr1b-Cre knockin mice 5 , in which Avpr1b is inactivated by the Cre recombinase coding sequence insertion and is expressed in CA2 pyramidal neurons, with mice containing loxP (f) sites flanking the Oxtr gene 19 . Homozygous Oxtr -floxed mice ( Oxtr f/f ) do not differ from WT littermates and express normal amounts of Oxtr 19 .…”

“…The pyramidal neurons in CA2 co-express the vasopressin (Avp) 1b and oxytocin (Oxt) receptors (Avpr1b and Oxtr, respectively), through which the important neuropeptides, Avp and Oxt , carry their modulatory action on social cognition and social behavior [5][6][7] . Previously, we showed that loss of the Avpr1b from the pyramidal neurons of the CA2 results in inability of mice to recognize a familiar conspecific [6][7] .…”

Incorporating the image formation process into deep learning improves network performance in deconvolution applications

“…The mouse brain sample was prepared using the iDISCO+ procedure 21 , followed by immunolabelling with Alexa Fluor 555-conjugated secondary antibody against anti-tdTomato primary antibody. The entire brain volume after dual-view reconstruction spanned 10280 × 5160 × 1400 voxels (corresponding to 4 × 2 × 0.5 mm 3 , 138.3 GB in 16-bit format) 22 . We trained on 12 randomly selected subvolumes of single-view data to predict the dual-view joint deconvolved results, each comprising 128 × 128 × 128 voxels, then applied the model to a held-out, larger scale subvolume from the same dataset spanning 1184 × 1184 × 1218 voxels.…”