Higher cognitive functions such as attention have been difficult to model in genetically tractable organisms. In humans, attentiondistracting stimuli interfere with trace but not delay conditioning, two forms of associative learning. Attention has also been correlated with activation of anterior cingulate cortex (ACC), but its functional significance is unclear. Here we show that a visual distractor interferes selectively with trace but not delay auditory fear conditioning in mice. Trace conditioning is associated with increased neuronal activity in ACC, as assayed by relative levels of c-fos expression, and is selectively impaired by lesions of this structure. The effects of the ACC lesions are unlikely to be caused by indirect impairment of the hippocampus, which is required for mnemonic aspects of trace conditioning. These data suggest that trace conditioning may be useful for studying neural substrates of attention in mice, and implicate the ACC as one such substrate. Selective attention is thought to contribute to conscious awareness, but its neural basis is poorly understood. The search for the neural substrates of attention has been concentrated in the primate visual system (1, 2). Although extremely useful for identifying neural correlates of attention, primates offer limited accessibility for functional perturbation experiments, prompting a search for alternative animal models more amenable to tests of causation. Although some attentional models have been established in rats (3), they depend on operant conditioning paradigms that have proven difficult to extend to mice, and require lengthy training periods.Studies in humans have suggested that attention is required for certain forms of associative learning (4). Associative learning paradigms, such as fear conditioning, have been successfully extended from rats to mice (5). Two commonly used variants of this procedure are delay and trace conditioning. In delay fear conditioning, a conditioned stimulus (CS), such as a tone, is immediately followed by an unconditioned stimulus (US), such as a foot shock. In trace conditioning, a time gap is introduced between the end of the CS and the start of the US. In human eye blink conditioning, another associative learning paradigm, distracting stimuli interfere with trace but not delay conditioning, suggesting that attention is necessary for the former type of learning (4, 6-10). More recent studies have suggested a similar requirement for attention in trace but not delay fear conditioning in humans (11).Potential neural substrates of attention have been identified by functional imaging in humans. For example, attention has been correlated with increased activity in the anterior cingulate cortex (ACC) (12-17). Furthermore, the ACC is preferentially activated during presentation of the conditional stimulus, compared with that of a meaningless stimulus, during aversive trace conditioning (18). The ACC has also been implicated in tasks requiring visual attention in rats (3,(19)(20)(21)(22)(23). Lesion studies have show...

Cannabinoids have been implicated in a variety of cognitive processes in humans, including attention, learning, memory, and time estimation. However, studies of the effects of cannabinoids on rodent behavior have focused on motor, learning, and memory tasks. To assess cannabinoid effects on time perception, this study examined whether systemically administered cannabinoid receptor agonists and a cannabinoid receptor antagonist influenced rats' performance of a time interval estimation task based on a fixed-interval schedule (a "peak procedure"). Both cannabinoid agonists WIN 55,212-2 and delta9-tetrahydrocannabinol shortened the modal response time, and cannabinoid antagonist SR 141716A lengthened the modal response time. Secondary measures of the shape of the response distribution were not influenced by any of the drugs, suggesting that the response distribution shifts were not artifacts of drug side effects. Therefore, these experiments argue for the involvement of endogenous cannabinoids in time estimation.