Circadian time-place learning in mice depends on Cry genes.
Endogenous biological clocks allow organisms to anticipate daily environmental cycles. The ability to achieve time-place associations is key to the survival and reproductive success of animals. The ability to link the location of a stimulus (usually food) with time of day has been coined time-place learning, but its circadian nature was only shown in honeybees and birds. So far, an unambiguous circadian time-place-learning paradigm for mammals is lacking. We studied whether expression of the clock gene Cryptochrome (Cry), crucial for circadian timing, is a prerequisite for time-place learning. Time-place learning in mice was achieved by developing a novel paradigm in which food reward at specific times of day was counterbalanced by the penalty of receiving a mild footshock. Mice lacking the core clock genes Cry1 and Cry2 (Cry double knockout mice; Cry1(-/-)Cry2(-/-)) learned to avoid unpleasant sensory experiences (mild footshock) and could locate a food reward in a spatial learning task (place preference). These mice failed, however, to learn time-place associations. This specific learning and memory deficit shows that a Cry-gene dependent circadian timing system underlies the utilization of time of day information. These results reveal a new functional role of the mammalian circadian timing system.
Van der Zee
Eddy A
EA
Department of Molecular Neurobiology, University of Groningen, P.O. Box 14, 9750 AA Haren, The Netherlands. e.a.van.der.zee@rug.nl
Havekes
Robbert
R
Barf
R Paulien
RP
Hut
Roelof A
RA
Nijholt
Ingrid M
IM
Jacobs
Edwin H
EH
Gerkema
Menno P
MP
D000818:Animals; D001245:Association Learning / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D056931:Cryptochromes; D005420:Flavoproteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; D005420:Flavoproteins