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Biomedical subjects

D M Wilkie

Publications and source records attributed to D M Wilkie.

At least 19 recordsLinked to original sources

Spatial working memory and hippocampal size across pregnancy in rats.

The present experiments investigated the effects of pregnancy on performance in the Morris water maze and on hippocampal volume. In the first study, pregnant rats (in between the first and second trimester) outperformed nonpregnant rats on the Morris water maze on 1 day of testing. In the second study, rats were tested in a working memory variation of the maze in which the spatial location of the platform varied. Pregnant females traveled shorter distances than nonpregnant females during the first two trimesters, but performed worse than nonpregnant females during the third trimester. Latency measures showed a similar profile. Group differences in performance were not related to changes in swim speed. However, changes in performance in pregnant females may be related to estrogen, progesterone, and/or corticosterone levels during pregnancy, with low levels of estradiol and high levels of progesterone being associated with better performance. There were no significant differences between pregnant and nonpregnant animals on any of the brain measures, although pregnant animals tended to have a smaller hippocampus than nonpregnant animals. These results indicate that pregnancy can affect performance, possibly related to the hormonal changes that accompany pregnancy.

Animals↗

Errors made by animals in memory paradigms are not always due to failure of memory.

It is commonly assumed that errors in animal memory paradigms such as delayed matching to sample, radial mazes, and food-cache recovery are due to failures in memory for information necessary to perform the task successfully. A body of research, reviewed here, suggests that this is not always the case: animals sometimes make errors despite apparently being able to remember the appropriate information. In this paper a case study of this phenomenon is described, along with a demonstration of a simple procedural modification that successfully reduced these non-memory errors, thereby producing a better measure of memory.

Animals↗

Rats use an ordinal timer in a daily time-place learning task.

Rats received 2 daily sessions in a large clear chamber. A lever was mounted on each of the 4 chamber walls. For each rat, a different lever provided food during 0930 and 1530 sessions. The rats learned which lever would provide food at 0930 and 1530. Probe tests suggested that the rats learned to press 1 lever during their 1st session of each day and to then press a 2nd lever during their 2nd session of each day. We propose that this knowledge of the order of a set of events within a period of time constitutes ordinal timing. We contrast the temporal information provided by ordinal, phase, and interval timing and consider why multiple timing systems have evolved in animals.

Animals↗

Discrimination of ovarian steroids by rats.

Rats' ability to discriminate their hormonal states was examined by observing the effects of ovarian steroids on state-dependent learning using a drug discrimination task. A rat's entry into the correct arm (left or right) of a Y-maze terminated mild foot shock. The arm designated as correct was alternated daily, but was consistently paired with a pretrial injection of hormone or vehicle. In Experiment 1, ovariectomized rats successfully discriminated pretreatment with 4.0 or 8.0 mg/kg progesterone vs. the oil vehicle but not 2.0 or 0.5 mg/kg progesterone vs. oil, or the daily alternation schedule alone (oil vs. oil). In Experiment 2a, ovariectomized rats correctly discriminated pretreatment with progesterone (4 mg/kg) vs. oil or dihydroprogesterone (4 mg/kg) vs. oil, and the results of Experiment 2b, appear consistent with the possibility that the rats discriminated pretreatment with progesterone vs. dihydroprogesterone. In Experiment 3a, ovariectomized rats discriminated on the basis of progesterone (4.0 mg/kg) vs. oil, estrogen (6.4 micrograms/kg estradiol benzoate) vs. oil, and estrogen vs. progesterone. In Experiment 3b, the rats were adrenalectomized, and the procedure from Experiment 3a repeated. The removal of the adrenal glands failed to abolish hormonal discriminations, suggesting that the effect is not adrenally mediated. The results of these studies show that rats can discriminate relatively low doses of ovarian steroids.

20-alpha-Dihydroprogesterone↗

The spatial distribution of pigeons' target detection.

Pigeons were trained to detect briefly-presented targets that appeared on a flatscreen computer display. Pecks were detected by a touchscreen mounted on the display. Those that were directed at the targets produced grain reward whereas pecks at locations in which the target had not appeared did not produce reward. A "behavioral fixation" procedure was used to ensure that the pigeons were facing the display when the target was presented. In general, the probability of detecting a target was highest in the region surrounding the fixation point and decreased as the target appeared more peripherally, both horizontally and vertically. These results show that pigeons' ability to detect targets in a frontal plane is not uniform.

Animals↗

Time-place learning by pigeons, Columba livia.

In each of two experiments, 2 pigeons received discrimination training in which food reinforcement for key pecking was conditional upon both spatial and temporal cues. In Experiment 1, food was available for periods of 30 s at each of three locations (pecking keys) during trials that lasted 90 s. In Experiment 2, food was available for periods of 15 min at each of four locations (pecking keys) during a 60-min trial. In both experiments, pigeons' key pecking was jointly controlled by the spatial and temporal cues. These data, and other recent experiments, suggest that animals learn relationships between temporal and spatial cues that predict stable patterns of food availability.

Journal Article↗

Discrimination training facilitates pigeons' performance on one-trial-per-day delayed matching of key location.

Six pigeons were tested on a one-trial-per-day variant of delayed matching of key location. In one condition, a trial began with the illumination of a pair of quasi-randomly selected pecking keys in a large 10-key test box. Pigeons' pecks to one key (the sample) were reinforced with 8-second access to grain on a variable-interval 30-second schedule, whereas pecks to the other key (the distractor) had no scheduled consequences. In the second condition, the nonreinforced distractor was not presented. In both conditions, subjects were removed from the apparatus after 15 minutes and placed in a holding cage. Subjects were subsequently replaced in the box after a delay (retention interval) of 30 seconds and were reexposed to the illuminated sample and distractor keys for 1 minute. If a pigeon made more pecks to the sample during this interval, the distractor was extinguished and subsequent pecks to the sample were reinforced on the previous schedule for an additional 15 minutes. If, however, a pigeon made more pecks to the distractor, both keys were extinguished and the subject was returned to its home cage. For all subjects, matching-to-sample accuracy was higher in the first condition. In a second experiment, the retention interval was increased to 5, 15, and 30 minutes, and then to 1, 2, 4, 8, 12, and 24 hours. Most subjects remembered the correct key location for up to 4 hours, and in one case, up to 24 hours, demonstrating a spatial-memory proficiency far better than previously reported in this species on delayed matching tasks. The results are discussed in terms of the commonly held distinction between working and reference memory.

Journal Article↗

Rats' short-term memory for brief electrical stimulation of the ventral tegmental area of the brain.

Short-term memory for brief electrical stimulation of rats' ventral tegmentum was assessed in a delayed conditional discrimination procedure in which trials began with a train of either low- or high-intensity stimulations. After a delay (i.e., retention interval) ranging from 0.01 to 4 sec, a lever was inserted, accompanied by a dim or a bright light. Lever-pressing was rewarded with food on low intensity-dim light and high intensity-bright light trials, but not on low-bright or high-dim trials. Discrimination ratios, based on relative responding on rewarded trials, indicated that subjects were able to remember the electrical stimulations, but that there was sometimes substantial forgetting after the 4-sec retention interval. The implications of these results for an understanding of the stimulus properties of electrical brain stimulation were discussed.

Animals↗

Effects of superior colliculus lesions on rats' orienting and detection of neglected visual cues.

Superior colliculus lesions generally result in a deficit in visual orienting described as sensory neglect. This observation was confirmed in this study: Rats with lesions did not orient to some stimuli that intact rats readily oriented to. However, rats with lesions did orient to stimuli that the intact rats treated as more salient. Also, when the less salient stimuli signaled aversive stimulation, the rats with lesions detected these stimuli. These findings suggest that superior colliculus lesions do not affect the detection of visual stimuli that have been neglected.

Animals↗

Rodents' (Rattus, Mesocricetus, and Meriones) use of learned caloric information in diet selection.

When given a choice between two mashes of equal caloric density but differing flavors, rats (Rattus norvegicus) show a robust preference for the flavor previously associated with a higher calorie food. This finding suggests that rats may identify food quality by sensory cues such as taste. Our initial attempt to show this effect in the golden Syrian hamster (Mesocricetus auratus) failed, apparently because of this species's tendency to store both high- and low-calorie mashes in their cheek pouches during conditioning trials. Initially we attempted to circumvent this seeming morphological constraint on learning by presenting low- and high-calorie mashes on alternate days. This procedure too failed to produce evidence of flavor-caloric learning, although this procedure produced robust learning in another rodent, the Mongolian gerbil (Meriones unguiculatus). Another method of preventing cheek pouching--concurrently presenting low- and high-calorie liquid diets--was more successful; then, hamsters showed clear evidence of flavor-caloric learning. Thus, although flavor-caloric learning is demonstrable in species of rodent besides the rat, the circumstances under which it occurs vary.

Animals↗

Dissociation of dopaminergic and non-dopaminergic substrates for cues produced by electrical stimulation of the ventral tegmental area.

The present study provides evidence for the existence of multiple substrates for cues produced by electrical stimulation of the ventral tegmental area in rats. Two different procedures were employed to assess the effects of amphetamine and haloperidol on the discrimination of high and low intensity cues produced by electrical brain stimulation (EBS). When the procedure involved frequent presentation of brief trials, amphetamine and haloperidol had no effect on the discrimination of EBS. In contrast, when the trials were less frequent and extended in duration, amphetamine enhanced the perceived intensity of the cues whereas haloperidol had the opposite effect. These results indicate that the use of different discrimination procedures may result in the measurement of separate dopaminergic and non-dopaminergic substrates for cue properties of EBS in the ventral tegmental area.

Amphetamine↗

Differential effects of physostigmine on cues produced by electrical stimulation of the ventral tegmental area using two discrimination procedures.

Two procedures were employed to assess the effects of physostigmine on the discrimination of cues produced by either high or low intensity electrical brain stimulation (EBS) of the ventral tegmental area in rats. When the procedure involved frequent presentation of brief trials, physostigmine enhanced the perceived intensities of the cues, causing the rats to respond to low intensities as though they had higher values. In contrast, physostigmine had no effects on the discrimination when the trials were less frequent and extended in duration. These results confirm the existence of multiple substrates for cues produced by stimulation of the ventral tegmental area in rats and implicate cholinergic neurons as substrates for the non-dopaminergic cues identified in the companion paper.

Animals↗

Long-term increases in dentate granule cell responsivity accompany operant conditioning.

The efficacy of synaptic transmission from the perforant path (PP) to the granule cells in the dentate gyrus (DG) of freely moving rats was monitored electrophysiologically over the course of training in an appetitively motivated, discriminated operant paradigm. Every day, 22 hr after behavioral sessions, evoked potentials were recorded from the DG following stimulation of the PP over range of current intensities and the amplitudes of the population spikes were measured. Behavioral conditions involved training in an operant conditioning paradigm or a session of free-feeding. Significant increases in population spike amplitudes were observed over the 8 d of training, but not over the 8 d of free-feeding. This training-induced increase in granule cell responsivity persisted for at least 10 d following the cessation of behavioral trials and was in many ways comparable to long-term potentiation (LTP), subsequently observed in these same rats 24 hr after tetanic stimulation. These data confirm and extend previous reports of synaptic enhancements following conditioning and suggest that such increases in synaptic efficacy may encode some aspect of learning.

Animals↗

Pigeons' spatial memory: II. Acquisition of delayed matching of key location and transfer to new locations.

Five hungry pigeons first received delayed matching of key location training. Trials began with a "ready" stimulus (brief operation of the grain feeder). Then one (randomly chosen) of a set of four keys from a three-by-three matrix was lit briefly as the sample. After a short delay (retention interval), the sample key was lit again along with one of the other eight keys. A peck at the key that had served as the sample produced grain reinforcement, whereas a peck to the other key produced only the intertrial interval. After delayed matching of key location was learned, the remaining five key locations were introduced as samples. Four of the five birds performed at considerably above-chance levels on the novel sample trials during the first as well as subsequent sessions. These results suggest that pigeons sometimes learn the single rule-"choose the location that matches the sample." The relevance of these results to the issue of whether pigeons learn a generalized matching rule (i.e., a concept of "sameness") is discussed.

Animals↗

Pigeons' spatial memory: III. Effect of distractors on delayed matching of key location.

The effect of distractors on pigeons' delayed matching of key location was investigated. Baseline trials began with a "ready" stimulus (brief operation of the grain feeder). Then one (randomly chosen) key from a three-by-three matrix was lit briefly as the sample. After a short delay (retention interval) the sample key was lit again along with one of the other eight keys. A peck at the key that had served as the sample (correct comparison) produced grain reinforcement, whereas a peck to the other key (incorrect comparison) produced only the intertrial interval. In Experiment 1, a houselight distractor, presented during either the sample, retention interval, or choice phases of the trial, had little if any effect on accuracy of matching key location. In Experiment 2, one of three types of spatial stimuli was interpolated during the retention interval, or the interval was blank as during baseline trials. The three stimuli were: the sample (correct comparison) location for that trial, the incorrect comparison location for that trial, or one of the seven unused locations for that trial. Relative to blank trials, accuracy improved slightly on sample-interpolated trials, decreased slightly on unused location-interpolated trials, and decreased considerably on incorrect comparison-interpolated trials. In Experiment 3, retention intervals were blank or had one of six types of interpolation: the sample, the incorrect comparison, two presentations of the sample, two presentations of the incorrect comparison, the sample followed by the incorrect comparison, or the incorrect comparison followed by the sample.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Gerbils in space: performance on the 17-arm radial maze.

In Experiment 1 six hungry gerbils received six trials per day on a 17-arm radial maze. During each trial the subjects were allowed to choose freely among the arms, each of which contained a food pellet, until each arm had been visited once or until eight minutes had elapsed. An error was recorded when the subject entered a previously visited arm. The gerbils quickly learned not to re-enter previously visited arms and generally made errors on fewer than 15% of entries, performance comparable to that of the rat and superior to that of other species tested in the radial arm maze. The intertrial-interval duration did not affect accuracy of arm choices during acquisition but did influence asymptotic accuracy. Accuracy did not change systematically over the six trials. A high proportion of arm entries were to nearby arms. Errors occurred most often towards the end of a trial. Odor cues were not important. When the number of trials per day was reduced from six to one, accuracy deteriorated slightly. In Experiment 2 neither the transposition of extramaze cues nor the placement of the maze in a different room had large disruptive effects on accuracy. In Experiment 3 the addition of three explicit intramaze brightness cues aided accuracy, perhaps by permitting the subjects to decompose the large maze into three smaller mazes, although there was no direct evidence that this was the case. Implications of a number of these results for models of spatial maze performance were discussed.

Animals↗

Pigeons' spatial memory: factors affecting delayed matching of key location.

The delayed-matching-to-sample procedure was modified to study pigeons' spatial memory. Nine pecking keys, arranged as a three-by-three matrix, served as the spatial cues. Trials began with a brief "ready" stimulus (dimming of the houselight). Then a randomly chosen key was lit briefly as a sample. After a short delay the sample key was lit again along with one of the other eight keys. A peck at the key that had served as the sample produced grain reinforcement, where as a peck to the other key produced only the intertrial interval. After delayed matching of key location was learned, the effects of sample and delay duration, number of keys illuminated as sample and comparisons, and organization of three-key samples were studied. Matching accuracy decreased as sample duration decreased, delay increased, the number of locations serving as samples increased, the number and proximity of comparisons increased, and when the three-key samples were "discontinuous" rather than "lines".

Animals↗

Disruption of autoshaped responding to a single of brain-stimulation reward by neuroleptic drugs.

Repeated pairing of the onset of a stationary light (CS) that signalled electrical stimulation of brain-stimulation reward sites in the mesencephalon (US) resulted in autoshaped approach behavior to the CS. After acquisition of approach to the CS two groups of rats were injected with either pimozide (0.15, 0.50, or 1.0 mg/kg) or haloperidol (0.05, 0.10, or 0.15 mg/kg) prior to test sessions consisting of 30 CS-US pairings. Both neuroleptic drugs caused a significant dose-related attenuation of the autoshaped CS-approach. A within-session analysis of responding after treatment with the high dose of each drug indicated that most responses occurred in the first 10 trials, a result that appears to rule out a direct effect of the drugs on sensory processes and orientation. The effect of repeated testing with pimozide (1.0 mg/kg) or haloperidol (0.15 mg/kg) was compared to three sessions with CS alone (extinction). Autoshaped CS-approaches declined gradually over the three extinction sessions, in contrast to the immediate and sustained disruption of approaching during the three drug sessions. These data suggest that neuroleptic-induced suppression of autoshaped CS-approach with brain-stimulation reward cannot be attributed solely to a block of reward processes. It is suggested that neuroleptic drugs disrupt neural mechanisms by which signals of impending reward release pre-organized response patterns.

Animals↗