The effect of intruded events on peak time: the role of reinforcement history during the intruded event

Pigeons were studied in an extension of a study by Aum et al. [Aum, S., Brown, B.L., Hemmes, N.S. 2004. The effects of concurrent task and gap events on peak time in the peak procedure. Behav. Process. 65, 43-56] on timing behavior under a discrete-trial fixed-interval (FI) procedure during which 6-s intruded events were superimposed on peak-interval (PI) test trials. In Aum et al., one event consisted in termination of the timing cue (gap trial); the other was a stimulus in the presence of which subjects had been trained to respond under an independent random-interval (RI) schedule of reinforcement (concurrent task trial). Aum et al. found a disruption of timing on concurrent task trials that was greater than that on gap trials. The present study investigated history of reinforcement associated with intruded events as a possible explanation of this earlier finding. After training to peck a side key on a 30-s PI procedure, discrimination training was conducted on the center key in separate sessions; red or green 6-s stimuli were associated with RI 24s or EXT (extinction) schedules. During testing under the PI procedure, three types of intruded events were presented during probe trials--the stimulus associated with the RI (S+) or EXT (S-) schedule during discrimination training, or a gap (termination of the side-keylight). Intruded events occurred 3, 9, or 15s after PI trial onset. Effects of reinforcement history were revealed as substantial disruption of timing during the S+ event and relatively little disruption during the S- event. Intermediate effects were found for the gap event. Results indicate that postcue effects are at least partially responsible for the disruptive effects of the S+ event.     

The effect of an intruded event on peak-interval timing in rats: isolation of a postcue effect

The present experiment employed the peak-interval (PI) procedure to study the effect of an intruded cue on timing behavior. Rats were trained on a 30-s PI procedure with a tone cue. Subsequently, a 6-s flashing light was paired off-baseline with foot shock (Experiment 1) or presented alone (Experiment 2). Then, in test trials, the light cue was presented 9s prior to (before) or 3s after (during) the onset of the timing cue, or the light was omitted (probe). Results showed rightward shifts in peak time occurring on both before and during trials in both experiments. Peak shifts on during trials exceeded the reset prediction in Experiment 1. When PI functions for before and probe trials were normalized in peak rate and peak time, they superimposed better than when functions were adjusted additively along the time axis, suggesting that the light cue may engender a decrease in functional clock rate. The findings suggested that the intruded cue produced both intracue and postcue interference with timing that was enhanced by fear conditioning.     

Amphetamine affects the start of responding in the peak interval timing task

In this paper we investigate how amphetamine affects performance in a PI task by comparing two analyses of responding during peak trials. After training on 24 s fixed interval (FI-24) with 96 s peak trials, rats were given amphetamine for 4 consecutive days at doses of .5 and 1.0 mg/kg. Responses during peak trials were fitted with a Gaussian distribution to estimate the expected time of reinforcement from the peak time. A single trials analysis was also performed to determine the start time and stop time of the transition into and out of a high rate of responding on each peak trial. Amphetamine significantly decreased peak times as measured with the Gaussian curve fitting. However, in the single trials analysis, animals initiated responding significantly earlier, but did not stop responding earlier. Thus, fitting a Gaussian to the average performance across trials sometimes provides a different characterization of the timing process than does analyzing the start and stop of responding on individual trials. In the current experiment, the latter approach provided a more precise characterization of the effects of amphetamine on response timing.     

Reward magnitude and timing in pigeons

We investigated the interaction of motivation and timing by manipulating the expected reward magnitude during a peak procedure. Four pigeons were tested with three different reward magnitudes, operationalized as duration of food access. Each stimulus predicted a different reward magnitude on a 5 s fixed-interval schedule. Trials with different reward magnitudes were randomly intermingled in a session. Most pigeons responded less often and started responding later on peak trials when a smaller reward was expected, but showed no differences in response termination or peak times. Reward magnitude was independently corroborated through unreinforced choice trials, when pigeons chose between the three stimuli presented simultaneously. These results contribute to a growing body of evidence that the expected reward magnitude influences the decision to start anticipatory responding in tasks where the reward becomes available after a fixed interval, but does not alter peak times, nor the decision to stop responding on peak trials.     

Time sharing in rats: A peak-interval procedure with gaps and distracters

Four hypotheses (switch, instructional-ambiguity, memory decay, and time sharing) were evaluated in a reversed peak-interval procedure with gaps by presenting distracter stimuli during the uninterrupted timed signal. The switch, instructional-ambiguity, and memory-decay hypotheses predict that subjects should time through the distracter and delay responding during gaps. The time-sharing hypothesis assumes that the internal clock shares attentional and working-memory resources with other processes, so that both gaps and distracters delay timing by causing working memory to decay. We found that response functions were displaced both by gaps and by distracters. Computer simulations show that when combined, the memory-decay and time-sharing hypotheses can mechanistically address present data, suggesting that these two hypotheses may reflect different levels of analysis of the same phenomenon.     

Within-session modulation of timed anticipatory responding: When to start responding

The peak procedure is widely used in the study of interval timing with animals. Multiple timing measures can be derived from peak responding. These measures are typically presented as averages across many trials based on the implicit assumption that peak responding is stable throughout the session. We tested this assumption by examining whether peak responding changed over the course of the session in 45 mice that were trained on a fixed-interval 30-s schedule. All common measures of peak responding, except stop times, changed over the course of the session: start times increased, response rates and spreads decreased, and, although less reliably, peak times also shifted rightward. These results are congruent with a motivational interpretation, whereby increased satiety leads to the observed behavioral signature of within-session modulation of timed anticipatory responding.     

The role of time and timing in hominid dental evolution

Exactly when during evolution hominids acquired their extended extra-uterine growth period is a contentious issue. In order to shed light on the tempo and mode of ontogenetic changes during hominid evolution, research has focused on the pattern and, to a lesser extent, the rate of growth observed in the developing dentition of extant and extinct hominoid taxa. From these data, the absolute timing of events has often been inferred, either implicitly or explicitly. Differences in patterns of growth, especially of the eruption of teeth, are reasonably well documented among hominoids. However, data on the absolute timing of dental developmental events are much more scarce, rendering tentative all inferences about timing from patterns alone. Such inferences are even more tentative when they involve interpreting ontogenetic trajectories in extinct species such as Plio-Pleistocene hominids, which almost certainly had unique patterns of maturation. In order to contribute to the debate about possible relations between pattern and timing in the developing dentition, we have collated information that specifically relates to the absolute timing of developmental events in extant and extinct hominoids and, hence, also to the rate at which processes occur. In doing so, we have attempted to identify both developmental constraints and possible heterochronic processes that may have led to the extended growth period characteristic of humans. There appears to be growing evidence that evolution toward an extended hominid ontogeny did not follow a path that can be described as a simple heterochronic event.     

Time-sharing in pigeons: Independent effects of gap duration, position and discriminability from the timed signal

Previous data suggest that in a peak-interval procedure with gaps, memory for the pre-gap interval varies with the discriminability of the gap from the to-be-timed signal. Here we extend this finding by manipulating the pre-gap and gap intervals as well as the visual contrast between the gap and the to-be-timed signal. The delay in response function after the gap was found to vary with the duration and position of the gap. However, for each gap duration and position, the delay in response increased with the gap-signal contrast: at 60% gap-signal contrast pigeons continued to accumulate time during the gap, at 80% gap-signal contrast pigeons stopped timing during the gap, and at 100% gap-signal contrast pigeons reset their timing after the gap. Data are accounted for by a time-sharing model assuming two concurrent processes during the gap--time accumulation and memory decay controlled by the salience of the gap--whose interplay results in a continuum of responses in the gap procedure.     

Effects of d-amphetamine on the behavior of pigeons exposed to the peak procedure

The effects of d-amphetamine on pigeons' key-pecking under the peak interval (PI) procedure were investigated in two experiments. In experiment I the effects of doses of d-amphetamine from 0.75 to 3.0 mg/kg on responding under PI 30 and 45 s were studied for 10 successive days. Reductions in peak time and wait time were observed at both PI values and an increase in the width was found at PI 30 s. There was no evidence of tolerance. In experiment II, pigeons exposed to a PI 45 s schedule were administered doses of D-amphetamine of 1.5 and 3.0 mg/kg for 30 successive days. Reductions in peak time and wait time were found here. Evidence of tolerance was found in wait time, peak time and width of the distribution at the higher dose. In both experiments a rate-dependent effect of the drug was found in the portion of each peak trial before the time that food was delivered on reinforced trials; this effect was weaker after the customary time of food delivery. The rate-dependent effect for responses before food time, combined with little effect of the drug on responses after food time, is shown by simulation to be sufficient to account for the reduction in peak time, without the need to appeal to an internal clock mechanism.     

Time estimation by pigeons on a fixed interval: the effect of pre-feeding

Pigeons well trained on a fixed interval 10-s schedule of reinforcement were tested on the peak procedure. In a successive conditions design, they were either pre-fed or not in the experimental setting. Pre-feeding decreased the rate of responding. It also led to a maximum rate of responding that occurred 2-3 s later than in the control condition, where the maximum occurred at the usual time of reinforcement. The shift in peak time in response to pre-feeding shows that peak time may not be a pure measure of timing. The results are also interpreted in terms of timing theories.     

Evaluation of rate-dependency and internal clock effects of D-amphetamine

The impact of two doses of d-amphetamine on rats' peak-interval performance was evaluated at two different points of training: with minimum training, 20 sessions, and with extended training, 120 sessions. At both points of training, none of the doses changed the location of the peak time; however, both doses caused a significant increase in the standard deviation of the response distribution during peak trials. Both results are incompatible with some previous empirical results, and with timing accounts that assume that dopamine modulates the pacemaker rate, but are compatible with a rate-dependent effect.     

Deletion of alpha-synuclein decreases impulsivity in mice

The presynaptic protein alpha-synuclein, associated with Parkinson's Disease (PD), plays a role in dopaminergic neurotransmission and is implicated in impulse control disorders (ICDs) such as drug addiction. In this study we investigated a potential causal relationship between alpha-synuclein and impulsivity, by evaluating differences in motor impulsivity in the 5-choice serial reaction time task (5-CSRTT) in strains of mice that differ in the expression of the alpha-synuclein gene. C57BL/6JOlaHsd mice differ from their C57BL/6J ancestors in possessing a chromosomal deletion resulting in the loss of two genes, snca, encoding alpha-synuclein, and mmrn1, encoding multimerin-1. C57BL/6J mice displayed higher impulsivity (more premature responding) than C57BL/6JOlaHsd mice when the pre-stimulus waiting interval was increased in the 5-CSRTT. In order to ensure that the reduced impulsivity was indeed related to snca, and not adjacent gene deletion, wild type (WT) and mice with targeted deletion of alpha-synuclein (KO) were tested in the 5-CSRTT. Similarly, WT mice were more impulsive than mice with targeted deletion of alpha-synuclein. Interrogation of our ongoing analysis of impulsivity in BXD recombinant inbred mouse lines revealed an association of impulsive responding with levels of alpha-synuclein expression in hippocampus. Expression of beta- and gamma-synuclein, members of the synuclein family that may substitute for alpha-synuclein following its deletion, revealed no differential compensations among the mouse strains. These findings suggest that alpha-synuclein may contribute to impulsivity and potentially, to ICDs which arise in some PD patients treated with dopaminergic medication.     

Choice and timing in concurrent chains: effects of initial-link duration

Theories of timing have been applied to choice between delayed rewards by assuming that delays are represented in memory and that subjects sample from memory when choosing between alternatives. To search for covariation in single-trial measures of performance that might confirm this assumption, we used a procedure that allowed for convergent measurement of choice and timing behavior. Four pigeons responded in a concurrent chains/peak procedure in which the terminal links were fixed-interval (FI) 8s and FI 16s, across conditions the duration of the initial-link schedule was either short or long, and one quarter of the terminal links lasted for 48 s and ended without reinforcer delivery. Preference for the FI 8-s alternative was stronger with shorter initial links, replicating the 'initial-link effect'. Responding on no-food trials was unaffected by initial-link duration, and aggregated across trials, was typical of the peak procedure: response distributions were approximately Gaussian, with modes near the FI schedule durations, and variance was greater for the FI 16-s terminal link. Analysis of local measures of initial-link performance (e.g., pause to begin responding, time spent responding, number and duration of visits to each alternative, etc.) found that the initial-link effect was associated with an increase in the number and duration of visits per cycle to the nonpreferred alternative. Regression analyses showed that local initial-link measures contributed relatively little additional variance in predicting performance on individual no-food trials beyond that accounted for by FI schedule. Our results provide no clear evidence that initial- and terminal-link responding in concurrent chains are mediated by a common representation of terminal-link delays.     

In vitro response of lymphocytes to phytohemagglutinin (PHA) as studied with antiserum to PHA : II. Cell cycle analyses

The cell cycle and phase times of human lymphocytes responding to PHA have been analysed with the percent labelled metaphases (PLM) technique. The range of generation times (13–18 h) and DNA synthesis times (6.5–10.5 h) reported here compare well with previous measurements in the literature. Cycle analyses of the early responding cells of the initial response, selected with partial anti-PHA serum inhibition, and of restimulated cells yield relatively well-defined PLM curves. The short cycle times measured from these curves may reflect the early cycles after stimulation or a subpopulation of responding cells. Analyses at two times during both the initial and restimulation responses suggest that cycles lengthen with time after stimulation. The poor PLM curves of the initial response and the restimulation response of cells released from anti-PHA inhibition indicate considerable intercellular variation in cycle times. Cells in the initial long G 1 phase contribute to this variation. PHA dose does not appear to affect the cycle time.     

Reproductive Asynchrony and the Divergence of Hawaiian Crickets

Asynchrony in reproductive behavior may contribute to reproductive isolation among sympatric species. While the 38 cryptic species of the genus Laupala are primarily distinguished on the basis of variation in pulse rate of male calling songs, additional phenotypes, such as asynchrony in reproductive behavior, may contribute to reproductive isolation in this genus. Here we document similarities and differences in the diel timing of two reproductive behaviors, male singing activity and insemination events. Asynchrony in the diel timing of male singing behavior was observed between two sympatric species, Laupala cerasina and Laupala paranigra, in the field. An interpopulational comparison within L. cerasina did not reveal variation in diel behavior patterns of singing between two locations. Asynchrony in the timing of copulation and sperm transfer between L. cerasina and L. paranigra was documented in the laboratory. The observed pattern of asynchrony in both the field and laboratory could have arisen in a number of ways. One possibility is that species diverged in sympatry because of interspecific interactions, producing a pattern of reproductive character displacement. Alternatively, the observed asynchrony in reproductive behavior may have played a role in the process of community assembly within this recently diverged cricket genus. The presence of interspecific variation and the absence of intraspecific variation revealed by our study do not support a pattern of reproductive character displacement for diel reproductive behavior, suggesting that the differences seen between species were not caused by recent species interactions.     

Evidence that the effect of 5-HT2 receptor stimulation on temporal differentiation is not mediated by receptors in the dorsal striatum

5-HT2 receptor stimulation alters temporal differentiation in free-operant timing schedules. The anatomical location of the receptor population responsible for this effect is unknown. We examined the effect of a 5-HT2 receptor agonist and antagonists, injected systemically and into the dorsal striatum, a region that is believed to play a major role in interval timing. Rats were trained under the free-operant psychophysical procedure to press levers A and B in 50s trials in which reinforcement was provided intermittently for responding on A in the first half, and B in the second half of the trial. Percent responding on B (%B) was recorded in successive 5s epochs of the trials; logistic functions were fitted to the data from each rat to derive timing indices (T50: time corresponding to %B = 50; Weber fraction: [T75-T25]/2T50, where T75 and T25 are the times corresponding to %B = 75 and %B = 25). Systemic treatment with the 5-HT(2A/2C) receptor agonist 2,5,-dimethoxy-4-iodo-amphetamine (DOI) (0.25 mg/kg, s.c.) reduced T50; the 5-HT2A receptor antagonist MDL-100907 (0.5 mg/kg, i.p.) did not affect performance, but completely blocked the effect of DOI. DOI (1 and 3 microg) injected bilaterally into the dorsal striatum did not alter T50. The effect of systemic treatment with DOI (0.25 mg/kg, s.c.) was not altered by intra-striatal injection of MDL-100907 (0.3 microg) or the 5-HT2C receptor antagonist RS-102221 (0.15 microg). The ability of systemically administered MDL-100907 to reverse DOI's effect on T50 confirms the sensitivity of temporal differentiation to 5-HT2A receptor stimulation. The failure of intra-striatal MDL-100907 to antagonize the effects of DOI suggests that 5-HT2A receptors in the dorsal striatum are unlikely to be primarily responsible for DOI's effects on timing. Furthermore, the results provide no evidence for a role of striatal 5-HT2C receptors in DOI's effect on timing.     

Interactions between the benzodiazepine receptor antagonist Ro 15-1788 (flumazepil) and the inverse agonist beta-CCE: behavioral studies with squirrel monkeys

The effects of Ro 15-1788 and ethyl-beta-carboline-3-carboxylate (beta-CCE) were studied alone and in combination on the behavioral performances of squirrel monkeys. Under one procedure, performances maintained by food were suppressed by electric shock presentation (punishment or "conflict" procedure). Under a second procedure, responding was maintained either by food or electric shock delivery under a 5-min fixed-interval schedule. Doses of beta-CCE between 0.1 and 3.0 mg/kg, i.m., produced graded decreases in punished responding which were reversed by pretreatment with Ro 15-1788 (1.0 - 10.0 mg/kg, i.m.). Low doses of beta-CCE (0.03 - 0.3 mg/kg, i.m.) increased responding of monkeys maintained by shock presentation, but did not affect food-maintained responding; higher doses of beta-CCE decreased responding under both schedules. These effects of beta-CCE are opposite those produced by the benzodiazepines under this procedure. Ro 15-1788 (1.0 mg/kg i.m.) antagonized the effects of beta-CCE, producing a shift to the right in the dose-response curves. These findings provide further support for the view that beta-CCE and Ro 15-1788 produce effects mediated by the same benzodiazepine receptor recognition site.     

Combined organizational and activational effects of short and long photoperiods on spatial and temporal memory in rats

The present study examined the effects of photoperiod on spatial and temporal memory in adult Sprague-Dawley rats that were conceived and reared in different day lengths, i.e., short day (SD-8:16 light/dark) and long day (LD-16:8 light/dark). Both male and female LD rats demonstrated increased spatial memory capacity as evidenced by a lower number of choices to criterion in a 12-arm radial maze task relative to the performance of SD rats. SD rats also demonstrated a distortion in the content of temporal memory as evidenced by a proportional rightward shift in the 20 and 60 s temporal criteria trained using the peak-interval procedure that is consistent with reduced cholinergic function. The conclusion is that both spatial and temporal memory are sensitive to photoperiod variation in laboratory rats in a manner similar to that previously observed for reproductive behaviour.     

Effect of clozapine on interval timing and working memory for time in the peak-interval procedure with gaps

Previous research indicates that dopamine controls both the speed of an internal clock [Maricq, A.V., Church, R.M., 1983. The differential effects of haloperidol and methamphetamine on time estimation in the rat. Psychopharmacology 79, 10-15] and sharing of resources between the timer and other cognitive processes [Buhusi, C.V., 2003. Dopaminergic mechanisms of interval timing and attention. In: Meck, W.H. (Ed.), Functional and Neural Mechanisms of Interval Timing. CRC Press, Boca Raton, FL, pp. 317-338]. For example, dopamine agonist methamphetamine increases the speed of an internal clock and resets timing after a gap, while dopamine antagonist haloperidol decreases the speed of an internal clock and stops timing during a gap [Buhusi, C.V., Meck, W.H., 2002. Differential effects of methamphetamine and haloperidol on the control of an internal clock. Behav. Neurosci. 116, 291-297]. Using a 20-s peak-interval procedure with gaps we examined the acute effects of clozapine (2.0mg/kg i.p.), which exerts differential effects on dopamine and serotonin in the cortex and striatum, two brain areas involved in interval timing and working memory. Relative to saline, clozapine injections shifted the response functions leftward both in trials with and without gaps, suggesting that clozapine increased the speed of an internal clock and facilitated the maintenance of the pre-gap interval in working memory. These results suggest that clozapine exerts effects in different brain areas in a manner that allows for the pharmacological separation of clock speed and working memory as a function of peak trials without and with gaps.     

Acquisition of peak responding: What is learned?

We investigated how the common measures of timing performance behaved in the course of training on the peak procedure in C3H mice. Following fixed interval (FI) pre-training, mice received 16 days of training in the peak procedure. The peak time and spread were derived from the average response rates while the start and stop times and their relative variability were derived from a single-trial analysis. Temporal precision (response spread) appeared to improve in the course of training. This apparent improvement in precision was, however, an averaging artifact; it was mediated by the staggered appearance of timed stops, rather than by the delayed occurrence of start times. Trial-by-trial analysis of the stop times for individual subjects revealed that stops appeared abruptly after three to five sessions and their timing did not change as training was prolonged. Start times and the precision of start and stop times were generally stable throughout training. Our results show that subjects do not gradually learn to time their start or stop of responding. Instead, they learn the duration of the FI, with robust temporal control over the start of the response; the control over the stop of response appears abruptly later.