Co

I Dark □ Illuminated

¡Dissimilar ^Similar

FIGURE 12.5 Behavioral manipulations of nontemporal parameters of the gap procedure in rats. In all experiments the temporal parameters were kept constant in all groups and conditions. Left panel: Rats stop timing during a dark gap (filled bar) and reset timing after an illuminated gap (empty bar). (Adapted from Buhusi, C.V. and Meck, W.H., J. Exp. Psychol. Anim. Behav. Process, 26, 305-322, 2000.) Center panel: Rats stop timing during a silent gap when the ITI is filled with a white noise (dissimilar condition, filled bar) and tend to reset when both the gap and the ITI are silent (similar condition, empty bar). (Adapted from Buhusi, C.V. and Meck, W.H., Behav. Neurosci, 116, 291-297, 2002.) Right panel: Rats reset timing after a high-intensity gap (high, empty bars), but not after a low-intensity gap (low, filled bars). (Adapted from Buhusi, C.V. et al., J. Comp. Psychol., 2002.)

I Dark □ Illuminated

¡Dissimilar ^Similar

FIGURE 12.5 Behavioral manipulations of nontemporal parameters of the gap procedure in rats. In all experiments the temporal parameters were kept constant in all groups and conditions. Left panel: Rats stop timing during a dark gap (filled bar) and reset timing after an illuminated gap (empty bar). (Adapted from Buhusi, C.V. and Meck, W.H., J. Exp. Psychol. Anim. Behav. Process, 26, 305-322, 2000.) Center panel: Rats stop timing during a silent gap when the ITI is filled with a white noise (dissimilar condition, filled bar) and tend to reset when both the gap and the ITI are silent (similar condition, empty bar). (Adapted from Buhusi, C.V. and Meck, W.H., Behav. Neurosci, 116, 291-297, 2002.) Right panel: Rats reset timing after a high-intensity gap (high, empty bars), but not after a low-intensity gap (low, filled bars). (Adapted from Buhusi, C.V. et al., J. Comp. Psychol., 2002.)

In a different set of experiments, a group of rats were trained to time a 20-sec visual signal, and the ITI was dark and silent (similar condition) (Buhusi and Meck, 2002). The empty bar in the middle panel of Figure 12.5 shows the shift in peak time determined by a 5-sec dark, silent gap. Afterwards, the same rats were trained to time the same 20-sec visual signal, but the ITI was signaled by a white noise (dissimilar condition) (Buhusi and Meck, 2002). The middle panel of Figure 12.5 shows that when the ITI was noisy, a 5-sec dark, silent gap determined a significantly smaller shift in peak time (filled bar in the middle panel of Figure 12.5). In fact, in the dissimilar condition the rats used a perfect stop strategy. Presumably, rats allocate few resources to timing in the ITI, and during a gap similar to the ITI, and therefore tend to reset in the similar condition.

We also evaluated whether rats' response rule in the gap procedure is influenced by the intensity of the gap. Rats were trained to time the absence of a 20-sec visual signal, and the ITI was illuminated by a 2500-lux light. In the test phase, reversed (illuminated) gaps were presented for either 5 sec at a 5-sec pregap interval, 5 sec at a 10-sec pregap interval, or 10 sec at a 5-sec pregap interval. Most importantly, in each test session the intensities of both the gap and ITI were manipulated. The shift in the peak time of responding in test sessions with baseline intensity gaps, 2500 lux, relative to test sessions with gaps of higher intensity, 10,000 lux, is shown in the right panel of Figure 12.5. When gaps of high intentity, 10,000 lux, were presented halfway into the to-be-timed dark interval, rats reset their timing mechanism (open bars). In contrast, when gaps of low intensity, 2500 lux, were presented halfway into the to-be-timed dark interval, rats shifted their peak time significantly less (Buhusi et al., 2002). These results support the notion that the stop-reset mechanism is controlled by the intensity of the gap. Presumably, gaps of high intensity determine a reallocation of attentional resources away from the timing component of the task. Left with fewer resources, the timer is unable to correctly keep timing, and subjects restart timing after the gap. Conversely, signals of low intensity allow rats to use more resources, maintain in memory the pregap interval, and resume timing after the gap where they left off. These results support the hypothesis that interval timing is sharing attentional resources with other cognitive processes, and that, in addition to temporal parameters, the nontemporal features of events control the stop-reset functions of an internal clock (Buhusi et al., 2002).

12.4.3 Evidence for Dopaminergic Involvement in Attention Sharing

Dopaminergic neurons respond equally to reinforcers and to novel, salient stimuli that elicit orienting reactions (Lee et al., 1998; Schultz et al., 1993) regardless of whether the salience derives from reward properties or from physical characteristics of the stimulus (Horvitz et al., 1997). Moreover, genetic manipulations of the dopam-ine reuptake transporter in mice suggest that an increase in the levels of striatal dopamine correlates with a state of hyperactivity, suggesting a deficit in selective attention (Gainetdinov et al., 1998). These data suggest that dopamine involvement in the speed of an internal clock needs to be dissociated from the possible confounder with attentional effects.

Gap ■ Similar —□—Dissimilar —a—Dissimilar + MAP

FIGURE 12.6 Behavioral and pharmacological manipulations act on the same chain of processes. Rats were first trained with a silent ITI and tested with silent gaps (similar condition.) When trained with a noisy ITI and tested with silent gaps (dissimilar condition), rats substantially decreased their shift after a gap. Acute administration of methamphetamine in the dissimilar condition (dissimilar + MAP) counteracted the effect of filling the ITI with white noise. (Adapted from Buhusi, C.V. and Meck, W.H., Behav. Neurosci., 116, 291-297, 2002.)

Assuming that dopaminergic agonists increase the perceived salience of interrupting events (see Gray et al., 1997), one might expect the gap to affect timing more under the influence of MAP (reset rule) and less under the influence of HAL (stop rule). Indeed, the results reviewed in Section 12.3.3 suggest that the stop-reset mechanism is affected by acute administration of dopaminergic drugs: MAP tends to increase the shift in peak time toward resetting timing, and HAL tends to decrease the shift in peak time toward stopping timing.

In a separate set of experiments we addressed the question of whether the behavioral and dopaminergic manipulations discussed above affect the same chain of processes, possibly related to attention sharing. Specifically, if these manipulations affect the same chain of processes, one would expect that the stopping effect of filling the ITI discussed in Section 12.4.2 would counteract the resetting effect of acute administration of MAP discussed in Section 12.3.3 when used simultaneously. Figure 12.6 shows the results of a set of experiments directed at testing this prediction.

A group of rats was trained to time a 20-sec visual stimulus, and the ITI was dark and silent. Rats were subsequently tested in four types of gap trials with dark, silent gaps (similar condition) of various durations, positioned at various pregap intervals. Figure 12.6 shows the shift in peak time produced by each of the four types of gaps. Subsequently, the same rats were retrained to time the same 20-sec visual signal, but the ITI was filled with white noise, and tested with the same silent gaps (dissimilar condition). In line with results discussed in Section 12.4.2, we found that dark, silent gaps produce a smaller shift when the ITI was noisy (dissimilar condition) than when the ITI was silent (similar condition). In the dissimilar condition, rats also received acute administration of indirect dopamine agonist metham-phetamine. In line with data discussed in Section 12.3.3, acute administration of

MAP shifted the response functions rightward (dissimilar + MAP condition), to about the same delay as in the similar condition. Importantly, in this experiment MAP administration determined a shift in peak time of about 10 sec, i.e., 50% of criterion interval, which is about three times more than previously reported clock speed effects (about 10 to 15% of criterion time) (Meck, 1983, 1986). This result strongly suggests that besides its clock effect, MAP affected another, perhaps atten-tional, mechanism. The effect of dopaminergic drugs during gap trials might reflect an alteration in the perceived salience of the interrupting event (e.g., Gray et al., 1997). This interpretation is supported by the fact that the shift in peak time in gap trials critically depends on nontemporal aspects of the paradigm, as shown by the differences between the similar and dissimilar conditions. Because MAP prevented the stopping effect of filling the ITI with white noise — a manipulation that affects the discriminability of the gap from the ITI — results suggest that MAP reset timing due to its attentional (stimulus controlled) effect rather than its clock effect. Most importantly, these behavioral and pharmacological manipulations seem to affect the same chain of processes because they antagonize each other when used simultaneously, as shown in this experiment.

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