Vasopressin 1b Receptor Knock-Out Impairs Memory for Temporal Order

Abstract

Mice lacking a functional vasopressin 1b receptor (Avpr1b) display decreased levels of aggression and social memory. Here, we used Avpr1b-knock-out (Avpr1b Ϫ/Ϫ ) mice to examine whether an abnormality of this receptor results in specific cognitive deficits in the domain of hippocampal function. Avpr1b Ϫ/Ϫ mice were deficient in sociability and in detecting social novelty, extending previous findings of impairment in social recognition in these mutants. Avpr1bϪ/Ϫ mice could recognize previously explored objects and remember where they were experienced, but they were impaired in remembering the temporal order of presentation of those objects. Consistent with this finding, Avpr1bϪ/Ϫ mice were also impaired on an object-odor paired associate task that involved a temporal discontiguity between the associated elements. Finally, Avpr1b Ϫ/Ϫ mice performed normally in learning a set of overlapping odor discriminations and could infer relationships among odors that were only indirectly associated (i.e., transitive inference), indicating intact relational memory. The Avpr1b is expressed at much higher levels than any other part of the brain in the pyramidal cells of hippocampal CA2 area, a subfield of the hippocampus that has physiological and genetic properties that distinguish it from subfields CA1 and CA3. The combined results suggest that the Avpr1b, perhaps in CA2, may play a highly specific role in social behavior and episodic memory. Because schizophrenia and bipolar disorder are associated with a unique pathology in CA2 and impairments in both social behavior and episodic memory, this animal model could provide insights into the etiology of these disorders.

Social memories in rodents: Methods, mechanisms and modulation by stress

“…Critically, the disruption of the vasopressinergic system in the OB did not affect object recognition or olfactory functions (Tobin et al, 2010). In agreement with these findings, object recognition was also intact in AVP1bR KO mice (DeVito et al, 2009). This suggests that AVP is important for the social component of social recognition because perturbations of this system do not appear to affect object recognition.…”

“…Accordingly, AVP1bR KO animals show reduced interest in a conspecific when given the choice to explore a juvenile vs. an empty compartment. In fact, AVP1bR KO mice did not show a significant social preference during the test, indicating a lack of social interest (DeVito et al, 2009). In the same study, social recognition of a juvenile conspecific was not detected in AVP1bR KO mice.…”

RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory

“…CA2 synapses are unusually stable and resistant to plasticity (LTP) following typical modes of stimulation (7). No previous studies implicate a role for the CA2 in spatial learning or memory except that it may be involved in social recognition memory and memory for temporal order (32). Yet, we show here that the loss of RGS14, a single CA2-enriched gene, abrogates this synaptic stability resulting in both robust LTP in CA2 neurons and an enhancement of spatial learning and object recognition memory.…”

Vasopressin V1a and V1b Receptors: From Molecules to Physiological Systems

“…V1bR-KO mice also showed a mild deficit in social recognition and memory for temporal order (119,533). V1bR-KO mice could recognize previously explored objects and remember where they were experienced, but their ability to remember the temporal order of the presentation of those objects was impaired (119).…”