Circadian time-place learning in mice depends on Cry genes

Eddy A. Van der Zee*, Robbert Havekes, R. Paulien Barf, Roelof A. Hut, Ingrid M. Nijholt, Edwin H. Jacobs, Menno P. Gerkema

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

82 Citaten (Scopus)
282 Downloads (Pure)


Endogenous biological clocks allow organisms to anticipate daily environmental cycles [1-3]. 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 [4-11], but its circadian nature was only shown in honeybees [1] and birds [5-7]. 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.

Originele taal-2English
Pagina's (van-tot)844-848
Aantal pagina's5
TijdschriftCurrent Biology
Nummer van het tijdschrift11
StatusPublished - 3-jun-2008

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