Working memory deficits in retinoid X receptor gamma-deficient mice.
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 RARbeta and RXRgamma. 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. RXRgamma appeared to be the functionally predominant receptor in modulation of the working memory, as RXRgamma, but not RARbeta 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 RXRgamma in frontal and perirhinal cortex, structures in which we detected RXRgamma expression and which are functionally implicated in working memory processes.
Wietrzych
Marta
M
Institut de Gaénétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut Clinique de la Souris (ICS), CNRS/INSERM/ULP, College de France, BP10142, 67404 Illkirch Cedex, CU de Strasbourg, France .
Meziane
Hamid
H
Sutter
Anne
A
Ghyselinck
Norbert
N
Chapman
Paul F
PF
Chambon
Pierre
P
Krezel
Wojciech
W
D000818:Animals; D007839:Functional Laterality / Q000502:physiology; D006185:Habituation, Psychophysiologic; D007150:Immunohistochemistry; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics* / Q000523:psychology*; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D018168:Receptors, Retinoic Acid / Q000502:physiology; D047491:Retinoid X Receptor gamma / Q000235:genetics / Q000502:physiology*; D013028:Space Perception / Q000502:physiology
D018168:Receptors, Retinoic Acid; D047491:Retinoid X Receptor gamma; C082925:retinoic acid receptor beta