Working memory deficits in retinoid X receptor γ-deficient mice

Abstract

Retinoid signaling has been recently shown to be required for mnemonic functions in rodents. To dissect the behavioral and molecular mechanisms involved in this requirement, we have analyzed the spatial and recognition working memory in mice carrying null mutations of retinoid receptors RARβ and RXRγ. Double mutants appeared deficient in spatial working memory as tested in spontaneous alternation in the Y-maze and delayed nonmatch to place (DNMTP) test in the T-maze. These mutant mice did acquire, however, spatial place reference or right/left discrimination tasks in the T-maze set-up, indicating that basic sensorimotor functions, spatial orientation, and motivational factors are unlikely to account for deficits in working memory-sensitive tasks. Double-mutant mice were also deficient in novel object recognition at intermediate, but not short delays. RXRγ appeared to be the functionally predominant receptor in modulation of the working memory, as RXRγ, but not RARβ single null mutant mice exhibited deficits similar to those observed in the double mutants. The mechanism of this modulation is potentially related to functions of RXRγ in frontal and perirhinal cortex, structures in which we detected RXRγ expression and which are functionally implicated in working memory processes.