Alterations in time-place learning induced by lesions to the rat medial prefrontal cortex

This experiment examined the effect of medial prefrontal lesions on time-place learning in the rat. During the first phase, prior to lesioning, rats received training on an interval time-place task. Food was available on each of four levers for 3 consecutive min of a 12-min session. The levers provided food in the same sequence on all trials. Rats restricted the majority of their presses on each lever to the time in each session when it provided food and were able to anticipate when a lever was going to provide food. During the second phase some rats received lesions that were restricted to the medial prefrontal cortex. Following these very restricted lesions, rats continued pressing a lever after it stopped providing food (i.e. perseverated, as if their internal clock was running slow). The third phase involved changing the order in which the levers provided food. Lesions had no discernable effect on the rats' ability to learn the correct sequence of food availability. However, this change made the rats' timing perseveration even more noticeable. Our results suggest the medial prefrontal cortex is not necessary for acquisition of time-place sequencing information. However, lesions do appear to produce perseveration on components of the sequence.     

How rats process spatiotemporal information in the face of distraction

How rats process spatiotemporal information in the face of distraction was assessed. Rats were trained on a time-place learning task in which the location of food availability depended on the amount of time elapsed since the beginning of the training session. In each training session each of four levers provided food pellets for 5 min on an intermittent schedule. In probe sessions interspersed with the final training sessions, the rats were presented with a second highly preferred food source-a piece of cheese-at various times into the session. Rats choose the correct lever after the cheese distraction, but it appeared that their internal clock had stopped during the cheese consumption period. Thus rats' internal clock, like that of pigeons, displays the properties of 'stop', 'reset', and 'restart'. Rat-pigeon differences in timing processes may be restricted to circadian or time of day timing. Present results also suggest that rats process spatial and temporal information separately.     

Some characteristics of spatial associative memory in the pigeon, Columba livia

Willson and Wilkie (1993) developed a novel procedure to assess pigeons' memory for the spatial location of food. Only one of four locations provided food each daily session. Each location consisted of an illuminated pecking key and grain feeder. Over different days different locations, randomly selected, provided food during a 16-min session. The pigeons tended to revisit the location at which food was found on the previous day thereby demonstrating memory for food-spatial location associations over 24 h. Three experiments were conducted to further investigate this phenomenon. In Experiment 1 the session duration was varied between 4 and 32 min. Longer sessions had no detectable effect on their ability to remember the rewarded location 24 h later, a result that suggests that only brief encounters with food at a particular location are necessary for recall. In Experiment 2 the necessity of an active search for the day's rewarded location was removed; a 5-min period in which only the rewarded key was lit preceded the regular 16-min session. Pecks to the lit key in this 5-min period produced grain on the standard schedule. This manipulation facilitated the pigeons' discovery of food but did not affect their ability to remember the rewarded location, suggesting that the process of search and discovery is not essential to the associative memory process. In Experiment 3, food was available during the complete session (non-depleting condition) or was available only during the first half of the session (depleting condition). No detectable differences in the birds' memory of yesterday's profitable location were found. This suggests that non-depletion of food is not a necessary condition for day-to-day recall of food location. Taken together these findings enlarge our understanding of the spatial associative memory process.     

Dynamics of choice and frequency of environment change

Recent research has examined the effects on behavioral adjustment of a range of within-session changes in the reinforcer ratio available from two alternatives. Regularities between extended patterns of behavior (choice) and a distribution of food deliveries (expressed as a food-rate ratio) have emerged from such studies. To assess the generality of these findings, the present study manipulated rats' experience in the choice situation. Sixteen rats were divided into two groups of eight rats each. Seven non-signaled food-rate ratios were arranged to occur for responses on two concurrently available levers. Group 1 experienced a different food-rate ratio every day; each ratio provided 70 food deliveries, and none of the seven ratios operated for 2 consecutive days. Group 2 experienced the same sequence of food-rate ratios, except that each food-rate ratio remained in effect for 17 consecutive days (providing 70 food deliveries per session), after which a different food-rate ratio was selected for the next 17 sessions. In all cases, preference was adjusted to changes in food-rate ratios. Estimates of sensitivity to changes in food-rate ratios increased with an increasing number of sessions (i.e., experience in the choice situation).     

Stimulus control over induction produced by upcoming food-pellet reinforcement

Research has demonstrated that rats increase their rate of lever pressing for sucrose reinforcement when food-pellet reinforcement will soon be available within the session. Recent results suggest that this increase occurs because stimuli in the session come to signal different levels of overall reinforcement. The present experiment tested this idea by having rats respond in two types of session. In one, they pressed lever A for 1% sucrose reinforcers in the first half of the session and lever B for food-pellet reinforcers in the second half (the opposing lever was retracted in the respective half). In the other, they pressed lever B for 1% sucrose reinforcers in the first half and lever A for 1% sucrose reinforcers in the second. Thus, the presence of lever A in the first half of the session was predictive of upcoming food-pellet reinforcement, but only lever B was ever used to obtain food pellets. Subjects responded at a higher rate on lever B in the first half of the session than on lever A, despite food-pellet reinforcement being unavailable in such sessions. Furthermore, they responded at a higher rate on lever B during probe sessions in which both levers were available. These results demonstrate that stimulus control over induction occurs when a stimulus becomes differentially associated with a heightened level of reinforcement. However, questions remain as to whether this association is Pavlovian or whether stimuli with "predictive value" may ever lead to induction.     

Dissociable anterograde amnesic effects of retrosplenial cortex and hippocampal lesions on spontaneous object recognition memory in rats

The amnesic effects of excitotoxic lesions of the rat retrosplenial cortex (RS) and hippocampus (HPC) in the spontaneous object recognition (SOR) performance were investigated. The SOR test consisted of the sample-exposure session(s) and a test session. First, to test retrograde amnesia, rats received four sample-exposure sessions within a day at 4 weeks and 1 day before the surgery, respectively. In the test sessions conducted 1 week after the surgery, both lesion groups showed a temporally ungraded retrograde amnesia. Second, to test anterograde amnesia, 1- and 4-week retention intervals were inserted between the four sample-exposure sessions and the test session. The RS-lesioned rats showed a retention interval-dependent impairment in the test sessions, while the HPC-lesioned rats showed an impairment regardless of the retention interval. Finally, to test short-term recognition memory, 5- or 30-min delay was interposed between the single sample-exposure session and the test session. Both lesion groups performed normally irrespective of the delay length. These results suggest that both the RS and HPC are important for long-term object recognition memory, but these areas have different roles in it. ? 2012 Wiley Periodicals, Inc.     

Reinforcer concentration effects on a fixed-interval schedule

Four rats received training on a mixed FI 30-s FI 150-s schedule, where the different FI values were associated with different levers. During baseline, the reinforcer was a 30% concentration of condensed milk. During subsequent testing sessions, the reinforcer concentration was varied within sessions over values of 10, 30, 50, and 70%. Measures of behaviour were taken from the FI 30-s lever during trials where the reinforcer was delivered for responses on the other lever. Increasing the reinforcer concentration which began the interval (a) increased the time to start responding in the interval, and (b) increased the location of the response peak on the FI 30-s lever (often to values well above 30s). Response rate at the peak, and spread of the response rate versus time function, changed much less with reinforcer concentration. The data are discussed relative to predictions derived from Scalar Expectancy Theory, the Behavioural Theory of Timing, and the Tuned-trace model.     

Ghrelin levels increase after pictures showing food

The neuropeptide ghrelin is a major signal for food intake in various species including humans. After exogenous ghrelin administration, food intake and body weight increase in rodents. In normal human subjects, ghrelin administration increases self-rated appetite and calorie intake and prompts the imagination of favorite meals. It is unclear so far whether ghrelin levels are affected by external cues such as sight of food. We investigated the influence of pictures showing food compared to neutral pictures on ghrelin levels in young normal male subjects (n = 8). The study consisted of two consecutive sessions with a one-week interval. During each session, blood for later analysis of plasma concentrations of ghrelin was collected between 08:15 and 13:00 every 15 min (between 10:30 and 11:30 every 10 min). Breakfast and lunch was provided at 08:30 and 12:00, respectively. Fifty pictures were presented from 10:30 to 10:45 showing neutral images during the first session and food contents during the second session. As expected, ghrelin levels increased before each meal independent of the picture contents. In addition, ghrelin levels during the 30-min interval following the presentation of pictures with food increased significantly compared to the 30-min interval before this presentation (area under the curve (AUC): 188 % vs. 158 %, P < 0.05). The difference in the increases between the two picture conditions was also significant (P < 0.05). Our findings suggest that sight of food elevates ghrelin levels in healthy volunteers.     

60 Hz electric fields and incandescent light as aversive stimuli controlling the behavior of rats responding under concurrent schedules of reinforcement

Several reports have shown that animals will sometimes engage in behaviors that reduce their exposure to a 60 Hz electric field (E-field). The field, therefore, can function as an aversive stimulus. In other studies, the E-field at equivalent strengths failed to function as an aversive stimulus. The present experiment, using rats, demonstrates how factors other than field strength can influence whether a subject engages in behavior that reduces field exposure. The general design consisted of giving the rat a choice between two alternatives, one of which sometimes included an added stimulus. Each subject was trained to press each of two levers to obtain food. Pressing one lever was reinforced intermittently under a variable interval 2 min schedule (VI 2); pressing the other lever was reinforced by a second VI 2 schedule operating independently of the first. Under this concurrent schedule the rat spent 50% of the daily 50 min session responding to each of the levers, indicating that they were equally “valued.” Next, while the schedules remained in effect, the first response to one of the levers turned on a 100 kV/m E-field which remained on until the rat pressed the other lever. The time spent responding under the schedule associated with the field was reduced by about 5–10%. When the procedure was changed so that no lever presses produced food, i.e., extinction, but the added stimulus contingency remained, the rats spent even less time in the presence of the field. Similar outcomes were observed during both the concurrent food or extinction schedules when incandescent light was used. Thus, both an E-field and incandescent light functioned as aversive stimuli, but the magnitude of the aversiveness was small. Aversiveness depended not only on stimulus intensity, but also on behavioral factors. Bioelectromagnetics 19:210–221, 1998. © 1998 Wiley-Liss, Inc.     

Interval time-place learning by rats: varying reinforcement contingencies

Two experiments with rats were conducted to study interval time-place learning when the spatiotemporal contingencies of food availability were more similar to those likely to be encountered in natural environments, than those employed in prior research. In Experiment 1, food was always available on three levers on a variable ratio (VR) 35 schedule. A VR8 schedule was in effect on Lever 1 for 5 min, then on Lever 2 for 5 min, and so forth. While rats learned to restrict the majority of their responding to the lever that provided the highest density of reinforcement, they seemed to rely on a win-stay/lose-shift strategy rather than a timing strategy. In Experiment 2, the four levers provided food on variable ratios of 15, 8, 15, and 30, each for 3 min. As expected the rats learned these contingencies. A novel finding was that the rats had a spike in response rate immediately following a change from a higher to lower reinforcement density. It is concluded that rats exposed to spatiotemporal contingencies behave so as to maximize the rate of obtained reinforcement.     

Short-term and long-term habituation of exploration in rats,hamsters and gerbils

Short-term (within-session) and long-term (between-session) habituation of exploratory behavior was studied in rats, hamsters and gerbils. Subjects were observed in an open field containing four different objects during three 15-min sessions with an 8–14 h interval between each session. Their exploratory activity was measured by the numbers of contacts they made with these objects. The three species differed from each other in both their long-term and short-term habituation of exploration. Rats showed disrupted between-session habituation because of an important initial burst of activity at the beginning of each session. In contrast, hamsters and gerbils displayed between-session habituation, but within-session habituation occured during the first session only. These results are discussed in relation both to the adaptive value of exploration, and to the natural habitat of each species.     

The Roman high- and low-avoidance rats respond differently to novelty in a familiarized environment

The purpose of the present study was to investigate the response to novelty in Roman high- and low-avoidance rats under non-stressful conditions. To reduce fear, a procedure of repetitive placing in the experimental chamber consisting of start, screen, and tunnel zones was applied. Each animal was placed in the experimental chamber daily for a 6min period. The first 11 sessions were the habituation sessions. In the 12th session, the novelty was introduced into the screen and tunnel zones. The subsequent two sessions were conducted under novelty conditions. Behavioral activities such as walking, object contacts, time spent in given zones, and entering the tunnels were measured. All the comparisons were made for two 3-min intervals, using a three-factor MANOVA, involving 2(sex)x2(subline)x8(3-mininterval). All subjects increased time spent in the tunnel zone, but RHA/Verh rats responded to a greater extent, especially the males. All subjects spent shorter times in the screen zone, but the RHA/Verh rats responded to a much greater extent. RHA/Verh rats, especially males responded with a substantial increase of time spent inside the tunnels. All subjects responded with an increased amount of object contacts. In general the RHA/Verh subjects showed a more pronounced response to novelty, as evidenced by a significant shift toward the tunnel zone. They spent more time in this zone than their RLA/Verh counterparts. Among the RLA/Verh rats, males tended to behave similarly to RHA/Verh rats, especially during the second 3min interval of session "12." The differences between the rat lines obtained in this study may be attributed to mechanisms specific to exploration, making them promising subjects to study the relationships between reactivity, novelty detection, adaptation, and environmental information processing.     

Intertrial interval as a contextual stimulus

Four experiments with rats investigated whether the time between appetitive conditioning trials can serve as a discriminative cue for responding during the next conditional stimulus (CS). In Experiment 1, rats that received extinction trials with a 4-min intertrial interval (ITI) showed spontaneous recovery after a retention interval of 16 min, whereas rats that received extinction with a 16-min ITI did not. Experiments 2 and 3 investigated more explicit discriminations between the 4- and 16-min ITIs. When a 16-min ITI signaled that the CS would be reinforced and a 4-min ITI signaled that it would not, the ITIs modulated responding to the CS. But when the 4-min ITI signaled reinforcement and the 16-min ITI did not, there was less evidence of modulation by the ITIs. This asymmetry was due at least partly to a difficulty in performance rather than learning. Experiment 4 investigated similar discriminations with 1- and 4-min ITIs. Here the results took a different form: time in the reinforced ITI elicited responding directly, but did not modulate responding to the CS. ITI can function as a contextual cue, and the results suggest new similarities between the processes behind interval timing and associative learning.     

Fewer peak trials per session facilitate acquisition of peak responding despite elimination of response rate differences

It has been shown in previous research [Kaiser, D.H., 2008. The proportion of fixed interval trials to probe trials affects acquisition of the peak procedure fixed interval timing task. Behav. Process., 77 (1), 100-108] that rats acquired peak responding sooner when fewer peak trials were presented during sessions of training with the peak procedure timing task. One potential problem with that research was that there were large differences in response rates among the groups. The present experiment attempted to examine the effect of proportion of peak trials when differences in response rate were controlled. Two groups of rats were each simultaneously tested with two versions of the peak procedure. One group was tested with 10% peak trials per session, and the other group was tested with 50% peak trials per session. For both of the groups, one of the panel lights and levers was associated with the traditional peak procedure. The other panel light and lever was associated with a similar peak procedure; however, reinforcement was provided at the end of each peak trial. This manipulation eliminated differences in response rate among the groups, however, Group 10% acquired peak responding more quickly than Group 50%, effectively replicating previous work in the absence of a response bias.     

Do rats time filled and empty intervals of equal duration differently?

The goal was to determine whether rats time filled and empty intervals of equal duration differently. Each of five rats was trained for 50 sessions on an instrumental appetitive head entry procedure in which food was available (primed) every 120 s. On "empty" cycles, 30s prior to the next food prime, a 0.5-s pulse of white noise was presented. On "filled" cycles, 30s prior to the next food prime, white noise came on and stayed on until food was delivered. The two types of cycles were presented with equal probability. The results showed that the rats timed both the food-to-food interval and the stimulus-to-food interval. A comparison of the response gradients on filled and empty cycles following stimulus presentation showed better temporal discrimination on filled cycles. The results were modeled using a Packet theory of timing, with a linear averaging rule to combine the temporal information provided by the stimulus and food. The model fits to the individual response gradients were evaluated with a Turing test.     

Effect of leptin on the acute feeding-induced hypothalamic serotonergic stimulation in normal rats

Both hypothalamic serotonin and leptin reduce energy intake and stimulate expenditure. There are evidence that increased serotonin metabolism may be involved in leptin actions. Using microdialysis, we directly assessed the effect of an intracerebroventricular leptin injection on 5-HT release in the lateral hypothalamus of normal rats. When LH microdialysates were collected in the absence of food intake, neither artificial cerebrospinal fluid (CSF) nor 10 microg leptin i.c.v. caused significant variations in 5-HT release, measured for 2 h post-injection, at 20-min periods. When food was ingested after CSF, 5-HT release increased significantly, with a maximal elevation of 51+/-16% above baseline occurring at the 100-120 min post-injection interval. Leptin inhibited food intake (-75% at 0-20 min and -73% at 20-40 min) while it accentuated the food-induced serotonergic activation. At the 0-20 min interval, serotonin release was significantly higher after leptin (42+/-12% above baseline) than after CSF (6+/-5%) and the maximal increase after leptin was of 126+/-53% above baseline (100-120 min, p>0.05 vs. CSF). These observations indicate that leptin probably interacts with the serotonergic-stimulating mechanisms elicited by food intake, intensifying them. The additional serotonergic activation induced by leptin may be significant for the hormone effects on energy balance.     

Haloperidol, dynamics of choice, and the parameters of the matching law

The idea that dopamine mediates the reinforcing effects of stimuli persists in the field of neurosciences. The present study shows that haloperidol, a dopamine antagonist, does not eliminate the reinforcing value of food reinforcers. The ratio of reinforcers changed seven times across two levers within sessions, modeling a dynamic environment. The magnitude of the reinforcer was manipulated independently of the reinforcer ratio. Four doses of intraperitoneal haloperidol were assessed over periods of 12 daily sessions. Haloperidol did not impair the discrimination that the rats established between rich and lean levers; the response distributions favored the lever associated with the higher probability of reinforcement and the larger pellets. The parameters of the generalized matching law (bias and sensitivity) were used to estimate effects of haloperidol upon the motor system and upon the rats' motivation for food reinforcers.     

Prior pregastric food stimulation and gastrin-releasing peptide1-27 (GRP) synergize to inhibit sham feeding.

The hypothesis that prior pregastric food stimulation is sufficient to reveal an inhibitory effect of gastrin-releasing peptide1-27 (GRP) on sham feeding was tested in 11 male rats equipped with chronic gastric cannulas. Rats were sham fed a high-carbohydrate solution during a 45-min test session, after 17-h food deprivation. GRP (16 or 32 microg/kg) or saline was injected intraperitoneally either at the onset or 5 or 15 min after the onset of sham feeding. This allowed for a 0-, 5-, or 15-min period of pregastric food stimulation before GRP or saline injections. Sham intake was recorded every 5 min, and behavior was observed every minute. GRP inhibited sham feeding when it was administered after 5 or 15 min of prior pregastric food stimulation, but not when it was administered at test onset. A nonsignificant increase in resting behavior and decrease in feeding behavior were associated with the decrease in sham feeding. No anomalous behaviors were noted. We conclude that a synergy between GRP and prior pregastric, presumably oral, food stimulation is sufficient to inhibit sham feeding.     

Habituation contributes to the decline in wheel running within wheel-running reinforcement periods

Habituation appears to play a role in the decline in wheel running within an interval. Aoyama and McSweeney [Aoyama, K., McSweeney, F.K., 2001. Habituation contributes to within-session changes in free wheel running. J. Exp. Anal. Behav. 76, 289-302] showed that when a novel stimulus was presented during a 30-min interval, wheel-running rates following the stimulus increased to levels approximating those earlier in the interval. The present study sought to assess the role of habituation in the decline in running that occurs over a briefer interval. In two experiments, rats responded on fixed-interval 30-s schedules for the opportunity to run for 45 s. Forty reinforcers were completed in each session. In the first experiment, the brake and chamber lights were repeatedly activated and inactivated after 25 s of a reinforcement interval had elapsed to assess the effect on running within the remaining 20 s. Presentations of the brake/light stimulus occurred during nine randomly determined reinforcement intervals in a session. In the second experiment, a 110 dB tone was emitted after 25 s of the reinforcement interval. In both experiments, presentation of the stimulus produced an immediate decline in running that dissipated over sessions. No increase in running following the stimulus was observed in the first experiment until the stimulus-induced decline dissipated. In the second experiment, increases in running were observed following the tone in the first session as well as when data were averaged over several sessions. In general, the results concur with the assertion that habituation plays a role in the decline in wheel running that occurs within both long and short intervals.     

Rats' memory for event duration in delayed matching-to-sample with nonspatial comparison response alternatives

Previous research has suggested that using stationary and moving levers as nonspatial response alternatives can significantly enhance the speed of acquiring a temporal discrimination in rats. In Experiment 1, rats were trained to discriminate 2 and 8s of magazine light illumination by responding to either a stationary lever or a moving lever with a cue light illuminated above it. Rats learned to discriminate event durations at a high level of accuracy after 25 sessions of training. During subsequent delay tests, rats exhibited a strong choose-long bias, indicating that they were timing from the onset of the magazine light until the entry of levers into the chamber. This occurred regardless of whether intertrial intervals and delay intervals were dark or illuminated. On test trials in which the sample was omitted, rats responded as if the short sample had been presented. In Experiment 2, the rats received extensive training with dark and illuminated variable delay intervals (1-4 s). However, they continued to exhibit a tendency to time from the onset of the magazine light until entry of the levers into the chamber. Although the use of stationary/uncued and moving/cued levers as response alternatives enhanced the speed of acquisition of the event duration discrimination in rats, additional procedural modifications will be necessary to prevent rats from timing during the delay interval.