Conditioned Stimulus Control in the Circadian System: Two Tales Tell One Story

One of the major outcomes of an unanticipated scientific finding is to stimulate research. Occasionally, further research results in the emergence of disputes the resolution of which often constitutes a scientific advance. This commentary was formulated as an attempt to resolve the divergent claims stemming from studies in our laboratory (Amir and Stewart, 1996; Arvanitogiannis and Amir, 1999) and the study by de Groot and Rusak (2000 [this issue]) pertaining to the ability of conditioned stimuli to control the circadian clock. As a point of departure, we took the findings of de Groot and Rusak at face value. Thus, instead of engaging in a rhetorical, point-by-point debate, our goal was to jointly evaluate the results from the two laboratories and, in the process, perhaps construct a framework geared toward a better understanding of the phenomenon at hand. This approach proved to be worthwhile. As we explain below, the results of the de Groot and Rusak study are in perfect agreement with what one would predict on the basis of our previous studies and from considering some theoretical issues concerning classical conditioning. Briefly, Amir and Stewart (1996) showed that a conditioned stimulus (CS) previously paired with light in Pavlovian conditioning trials can induce phase shifts in a manner similar to light. In that study, pairings of a CS with a distinctive light,1 the unconditional stimulus (US), were made at zeitgeber time 15 of a 12:12 light-dark cycle (LD). de Groot and Rusak used a conditioning paradigm similar to that used by Amir and Stewart (1996) but found no evidence for classical conditioning. Although similar, the two studies do have a fundamental difference in design that predictably led to the differences in results: de Groot and Rusak did not use a distinctive US. They, instead, used the same light stimulus as both the zeitgeber and the US. Thus, the arranged probability between the CS and light was 50%. In other words, the US was just as likely to occur in the absence of the CS as in its presence. Under these circumstances, the pairings of CS and US do not provide good evidence for a causal relationship. For animals to learn about a CS-US association, there must be an overall positive correlation between the two events: the probability that the US will occur in the presence of the CS must be greater than the probability that the US will occur in the absence of the CS. By using the same light stimulus as the US as was used for entrainment to an LD cycle, de Groot and Rusak inadvertently performed what is considered to be the ideal control experiment. They arranged a contingency between the CS and US that would reduce the probability of observing conditioning. Conditioning was indeed eliminated. This is good news: the phenomenon we are dealing with fits well within the framework of conditioning theory. de Groot and Rusak performed two additional experiments in which they assessed conditioning in animals maintained on a skeleton photoperiod in which two discrete light presentations were used as both the entraining lights and the unconditioned stimulus. This procedure has the potential to answer an important question: Can CS control of clock resetting develop when the light stimulus used as the US is the same as that used to entrain the rhythm? de Groot and