Dietary restriction inhibits spatial learning ability and hippocampal cell proliferation in rats1

Abstract: We investigated the effect of dietary restriction on spatial learning ability and hippocampal cell proliferation in adult rats using two spatial learning tasks and immunohistochemical staining with 5‐bromo‐2′‐deoxyuridine (BrdU). Sixteen rats were divided into restricted or ad lib feeding groups at 70 days of age, and were trained in the delayed‐matching‐to‐place (DMTP) task (a working memory task) from 93 days of age, and then the Morris water maze task (a reference memory task). Dietary restriction had no effect on the DMTP task with 30 s delay and on the water maze task. However, in the DMTP task with 30 min delay, restricted rats performed significantly more poorly than ad lib rats. Quantitative analysis of hippocampal cell proliferation revealed that the density of newborn cells in restricted rats was significantly lower than that in ad lib rats. These results suggest that a loss of proliferating capacity in the hippocampus may be a candidate for an anatomical and biological basis for the cognitive decline caused by dietary restriction.     

Effects of BIM-22015, an analog of ACTH4-10, on functional recovery after frontal cortex injury.

Male rats, 90-100 days old, with frontal cortex lesions were given either subcutaneous sterile water (SW) as a vehicle control or 1, 10, or 100 micrograms of BIM-22015 every other day for 20 days. Brain-injured subjects tested in the Morris water maze with either 10 micrograms BIM-22015 or SW took significantly more trials than sham-operated rats to locate a submerged platform eight consecutive times within 60 s. The animals given 1 or 100 micrograms BIM-22015 took significantly fewer trials to reach criterion than brain-injured animals in the other drug treatment groups. On a percentage of savings, measured 8 days after reaching criterion, the brain-injured subjects given 1, 10, or 100 micrograms BIM-22015 did not differ from sham-operated rats. In contrast, the brain-injured animals given SW took longer to find the submerged platform than they did during the initial training. To assess long-term effects of the ACTH analog treatment, rats were trained on a delayed spatial alternation task 30 days after receiving the last injection. On this task, brain-injured rats treated with the 10-micrograms dose performed significantly better than those given sterile water. Acetylcholinesterase (AChE)-labeled neurons counted in the nucleus basalis magnocellularis indicated that rats with frontal cortex damage given the 10-micrograms treatment did not differ from the sham controls and had significantly more AChE-positive neurons than injured counterparts treated with SW or 100 micrograms.     

On the effects of food deprivation and component reinforcer rates on multiple-schedule performance

Six pigeons were used to investigate the effects of varying body weight and component reinforcer rates in two-component multiple variable-interval variable-interval schedules. In Parts 1 and 3 of the experiment, unequal component reinforcer rates were arranged, and body weights were respectively increased and decreased. At 80% ad lib weight, response-rate ratios were closer to unity than reinforcer-rate ratios, but at 100% or more of ad lib weight, response-rate ratios generally equaled reinforcer-rate ratios. In Part 2, component reinforcer-rate ratios were varied over five conditions with the subjects maintained at 100% or more of their ad lib weights, and response-rate ratios matched reinforcer-rate ratios. The data thus support the empirical finding that response allocation in multiple schedules is a function of deprivation. Although this qualitative result is predicted by three models of multiple-schedule performance, only a model that assumes no direct component interaction adequately describes the data.     

Automatic testing of cognitive performance in baboons maintained in social groups

Laboratory procedures used to study the cognitive functions of primates traditionally have involved removal of the subjects from their living quarters to be tested singly in a remote experimental room. This article presents an alternative research strategy favoring testing primates while they are maintained in their social group. The automatic learning device for monkeys (ALDM) is a computerized test system controlled by an automatic radio frequency identification of subjects. It is provided ad lib inside the social group of monkeys, for voluntary self-testing on a 24-h schedule. Nine baboons were tested with ALDM during a 7-month period. Experiments were performed to assess learning in motor control and abstract reasoning tasks. The results revealed high trial frequencies and excellent learning performance, even in tasks involving the highest cognitive complexities. A different study using ALDM with a group of 3 rhesus monkeys revealed social influences on learning. Beyond its interest for cognitive psychologists, ALDM is of interest for pharmacologists and cognitive neuroscientists working with nonhuman primates. ALDM also can serve as an enrichment tool for captive animals and may be used to study a variety of species other than primates.     

Undernutrition during suckling and latent learning ability of rehabilitated adult male rats

The present report investigates the effects of early undernutrition on the latent learning ability of rehabilitated adult male rats in a simple maze task. Rats were undernourished during suckling by feeding their dams an 8% casein diet. Well-nourished dams received a 25% casein diet during the same period. Rats were weaned at 21 days of age and nutritionally rehabilitated until they became adults, when behavioral task was conducted. Under a nonappetitive condition, rats were exposed either to an open field or to a maze apparatus. They were thereafter deprived of water and tested in the maze apparatus. Both well-nourished and undernourished rats that had been previously exposed to the maze performed better than those exposed to the open field. Nutritional treatment had no effect on performance of either the latent learning or of the open-field groups. These results suggest that rehabilitated adult rats are able to learn about the environment when no immediate reinforcement is involved. The discrepancy between our findings and results reported by others may be due to differences in task complexity and/or perhaps to the fact that nutritional rehabilitation also plays a role in reversing some of the deleterious effects of early undernutrition on learning ability of rats.     

Spontaneous and learned turning behaviour in food- or water-restricted hooded rats

Some laboratory studies have suggested that whereas food restriction in animals leads to response alternation (behavioural flexibility), water restriction induces perseverative, stereotyped responding. Hooded rats, restricted to 1 hour per day access to either food or water, were tested on a radial-arm maze (using a procedure that eliminates algorithmic response strategies), for alternation in a 3-arm maze (both when the maze was familar and unfamilar, and with or without differential reward) and a 2-choice maze in which some animals were taught to alternate direction of turn, and others to perseverate. Both groups performed the radial-arm maze task competently and spontaneously alternated at a high rate. In the learned task, food-restricted rats were slower than water-restricted to reverse a consistent direction of turn; in the alternation condition, water-restricted rats developed a temporary, but strong, directional bias when making their first choice each day. Water-restricted subjects took water more readily than food-restricted took food when initially introduced to the apparatuses, but there was no consistent difference in motivation in the two conditions. The results provide little support for the notion that distinct cognitive-motivational states or behavioural strategies are induced by food- and water-restriction.     

Reinforcer devaluation in palatability-based learned flavor preferences

Rats exposed to simultaneous compounds of 1 neutral flavor with dilute (2%) sucrose and a 2nd flavor with dilute (2%) maltodextrin subsequently consumed both flavors in preference to a 3rd flavor that was never paired with a palatable taste. Brief training exposure under ad lib food and water minimized the post-ingestive effects of nutrients, emphasizing the contribution of palatability to these preferences. Devaluation of sucrose or maltodextrin by pairing with illness (Experiment 1) or sensory-specific satiety (Experiment 2) selectively reduced the preference for the flavor previously paired with the devalued reinforcer. Such reinforcer-specific devaluation effects suggest that palatability-based learned flavor preferences are under-pinned by a Pavlovian process whereby the cue flavor is associated with the taste of the concurrently consumed palatable reinforcer.     

Binocular rivalry alternation rate declines with age

The effect of aging on the time of spontaneous perceptual alternation in binocular rivalry was examined in 59 subjects. An earlier study reported the change of alternation time by comparing middle-age and elderly subjects. We also observed age-related prolongation in alternation time by comparing subjects in a lower age group (20-34 years) with those in both a middle-age group (35-49 years) and a higher age group (50-64 years). Aging of visual optical functions such as presbyopia or the reduction of contrast sensitivity has an accelerating effect over age and may not be related to the age-associated monotonic prolongation of alternation time in binocular rivalry. The origin of aging in binocular rivalry is still unclear but a neural interval generator for perceptual switching is suggested.     

Misled subjects may know more than their performance implies

Many studies have demonstrated that subjects exposed to misleading postevent information are likely to report the misinformation with confidence on subsequent tests of memory for the event. The purpose of the present studies was to determine whether subjects exposed to misleading postevent information come to believe they remember seeing the misinformation at the original event. A second question addressed by the present studies is whether exposure to misinformation reduces subjects' ability to remember the source of items they witnessed at the original event. In two experiments, subjects viewed a slide sequence depicting an event, were subsequently exposed to misleading information or neutral information about selected aspects of the event, and were later tested on their memory for the source of original and misleading details. The results showed that exposure to misinformation did not lead subjects to believe they remembered seeing the misinformation, nor did it reduce subjects' ability to accurately identify the source of originally seen details. The same pattern of results was obtained whether subjects were tested immediately (Experiment 1) or after a 1-day delay (Experiment 2). Collectively, the results suggest that subjects may report misinformation even if they know they do not remember seeing it.     

Comparison of social time-out and activity time-out procedures in suppressing ethanol self-administration in alcoholics

The experiments compared the potencies of three different contingent time-out procedures for suppressing drinking in alcoholics, and also compared two different experimental methodologies for conducting such studies. In a residential research ward setting fourteen volunteer chronic alcoholics were given daily access to 17 alcoholic drinks provided that a minimum of 40 min elapsed between receiving successive drinks. Each drink contained 1 oz 95-proof ethanol in orange juice. During the baseline condition subjects were free to drink with no behavioral restrictions. However during the time-out conditions, specific behavioral restrictions were imposed on the subjects for the 40-min period following receipt of each drink. The results showed that Social time-out suppressed drinking to 71 per cent of baseline conditions, while Activity time-out and the combined Social and Activity time-out suppressed intake to 36 and 24 per cent, respectively. The study also demonstrated that similar experimental results were obtained when subjects were continuously exposed to the experimental conditions for a number of consecutive days. or intermittently exposed to different conditions in a mixed order over successive days.     

Biased generalization of newly learned phonological alternations by 12-month-old infants

Previous work has suggested that learners are sensitive to phonetic similarity when learning phonological patterns (e.g.,  and ). We tested 12-month-old infants to see if their willingness to generalize newly learned phonological alternations depended on the phonetic similarity of the sounds involved. Infants were exposed to words in an artificial language whose distributions provided evidence for a phonological alternation between two relatively dissimilar sounds ([p ∼ v] or [t ∼ z]). Sounds at one place of articulation (labials or coronals) alternated whereas sounds at the other place of articulation were contrastive. At test, infants generalized the alternation learned during exposure to pairs of sounds that were more similar ([b ∼ v] or [d ∼ z]). Infants in a control group instead learned an alternation between similar sounds ([b ∼ v] or [d ∼ z]). When tested on dissimilar pairs of sounds ([p ∼ v] or [t ∼ z]), the control group did not generalize their learning to the novel sounds. The results are consistent with a learning bias favoring alternations between similar sounds over alternations between dissimilar sounds.     

Visual complexity and stimulus pacing in chicks

Two groups were tested for spontaneous alternation using massed and spaced trials but alternation rate was not above chance level. Two experiments then examined the use of visual stimuli as pacers for an approach response. The results indicate that subjects responded to complexity and that complexity may be a more effective pacer than novelty.     

Chronic perchlorate exposure impairs stickleback reproductive behaviour and swimming performance

We describe behavioural changes in two generations of threespine stickleback (Gasterosteus aculeatus) exposed to environmentally relevant concentrations of perchlorate. The first generation (G(0,2002)) was exposed as two-year-old adults to perchlorate in experimental groups ranging in concentration from less than the method detection limit (<1.1 ppb) to 18.6 ppm for up to 22 days during their courtship, spawning, egg guarding, and first five days of fry guarding. No differences were noted in the behaviour or reproductive output of these fish that were exposed as adults. However, perchlorate exposure throughout development caused widespread effects in the second generation (G(1,2003)), which was spawned and raised through sexual maturity in one of four nominal experimental groups (0, 30 and 100 ppm, and a 'variable' treatment that progressively increased from <1.1 ppb to approximately 60 ppm perchlorate). Dose-dependent effects were found during the G(1,2003)'s swimming and behavioural evaluations, including higher mortality rates among treated fish following stressful events. Perchlorate-exposed fish had higher failure rates during swimming trials and failed at lower flow rates than control fish. A number of treated fish exhibited seizures. Progressively fewer males completed benchmark metrics, such as nest building, spawning, nursery formation, or fry production, in a dose-dependent manner. Fewer males from higher treatments courted females, and those that did initiated courtship later and had a reduced behavioural repertoire compared to fish from lower treatments. The lowest observed adverse effect level (LOAEL) for swimming performance, reproductive behaviour, survivorship and recruitment was 30 ppm perchlorate (our lowest G(1,2003) treatment), and near complete inhibition of reproductive activity was noted among males raised in 100 ppm perchlorate. A small number of treated G(1,2003) females were isolated in aquaria, and some performed reproductive behaviour typical of males, such as biting, leading and zig-zagging in the presence of gravid females. These findings have profound implications for recruitment in wild fish populations exposed to perchlorate, and suggest that perchlorate may disrupt behaviour in other vertebrates as well.     

The effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage

Clozapine is an atypical antipsychotic drug that has been shown to improve spatial memory in some animal models; however its efficacy in reversing spatial memory impairment in rats with hippocampal lesions is unknown. To address this issue, we tested the effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage in three separate experiments. In each experiment, adult male rats received sham surgery or direct stereotaxic infusions of the excitotoxin, NMDA, into the hippocampus. In the first study, seven days after surgery, the sham control animals received daily saline injections while the lesioned animals were split into two groups that received daily saline or clozapine (2.0 mg/kg, sc) injections. During the fifth week of injections, all animals were tested in a food-motivated delayed spatial alternation task. Saline-treated rats with excitotoxic hippocampal damage displayed significant deficits in delayed spatial alternation. Daily clozapine injections completely reversed this deficit. In a second experiment, it was found that clozapine treatment limited to the testing days only did not improve alternation performance in lesioned rats. Finally, in a third experiment, chronic clozapine treatment did not improve alternation performance in lesioned rats that were pre-trained in the alternation task prior to surgery. These results suggest that chronic, but not acute, clozapine treatment enables rats with hippocampal damage to develop new spatial learning, but can not rescue old spatial learning established prior to damage. These results may have implications for the treatment of cognitive deficits caused by hippocampal dysfunction in disorders such as schizophrenia, Alzheimer's disease, and others.     

Electroencephalographic registration of low concentrations of isoamyl acetate

Previous research has demonstrated electroencephalogram (EEG) changes in response to low-odor concentrations, resulting in near-chance detection. Such findings have been taken as evidence for olfaction without awareness. We replicated and extended previous work by examining EEG responses to water-water control, 0.0001, 0. 001, 0.01, and 1 ppm isoamyl acetate (IAA) in water paired with water only. Detection was above chance (>50%) for.001 and above, and alpha decreased only to those concentrations, suggesting that EEG changes corresponded to IAA awareness. However, when correct trial EEGs were compared to incorrect trial EEGs during.001 ppm, right posterior/central alpha decreased during incorrect trials and alpha decreased more globally (including frontal sites) during correct trials. These data may not reflect awareness or unawareness per se. Instead, results are discussed regarding activation of perceptual systems in the posterior region during incorrect trials and the activation of frontal action systems during a subset of correct trials.     

Comparison of accuracy in auditory and tactile recognition memory for environmental stimuli.

Accuracy rates for auditory and tactile recognition of naturalistic stimuli over a 7-day period are compared. 40 subjects listened to 50, 107, or 194 naturalistic sounds and were tested immediately or after delays of 2 or 7 days. 30 other subjects handled but did not visually inspect 150 common objects and were tested over the same three delay intervals. Recognition accuracy for sounds was 87.5%, 82.5%, and 80.4% while common objects were recognized at 96.0%, 93.8%, and 88.5% rates of accuracy. Tactile recognition memory was superior to auditory recognition memory. The recognition accuracies of both modalities were affected by the delay interval. The number of items inspected had no effect on the recognition memory for sounds. Following a delay of 1 wk., the accuracy of recognition relative to the original level of function was 92% for both modalities.     

Automated testing of cognitive performance in monkeys: Use of a battery of computerized test systems by a troop of semi-free-ranging baboons (<Emphasis Type="Italic">Papio papio</Emphasis>)

Fagot and Paleressompoulle (2009) published an automated learning device for monkeys (ALDM) to test the cognitive functions of nonhuman primates within their social groups, but the efficiency of the ALDM procedure with large groups remains unknown. In the present study, 10 ALDM systems were provided ad lib to a troop of 26 semi-free-ranging baboons that were initially naive with computerized testing. The test program taught baboons to solve two-alternative forced choice (2AFC) and matching-to-sample (MTS) tasks. A million trials were recorded for the group during a period of 85 days (Experiment 1). Their analysis shows that 75% of the baboons participated at high frequencies and quickly learned the 2AFC and MTS tasks. In Experiment 2, we compared the baboons’ behavior when the ADLM systems were either accessible or closed. ALDM reduced frequencies of object-directed behaviors, but had no overt consequence on social conflicts. In Experiment 3, we tested the process of the global or local attributes of visual stimuli in MTS-trained baboons in order to illustrate the efficiency of ALDM for behavioral studies requiring complex experimental designs. Altogether, the results of the present study validate the use of ALDM to efficiently test monkeys in large social groups. ALDM has a strong potential for a variety of scientific disciplines, including for biomedical research. Supplemental materials for this article may be downloaded from http://brm.psychonomic-journals.org/content/supplemental.     

Peripheral oxytocin administration buffers autonomic but not behavioral responses to environmental stressors in isolated prairie voles

Negative social experiences such as social stressors and isolation influence mental and physical illnesses, including affective disorders and heart disease. Studies focused on socially monogamous prairie voles can provide insight into neurobiological systems that underlie the consequences of negative social interactions. Female prairie voles were exposed to 28 days of social isolation or pairing with a female sibling (control). Voles were administered daily oxytocin [20 μg/50 μl, subcutaneous (sc)] or saline vehicle (50 μl, sc) for 14 days and exposed to two behavioral stressors [elevated plus maze (EPM) and resident-intruder test]. Brain tissue was collected for analysis of central peptide levels in the hypothalamic paraventricular nucleus (PVN). Isolation produced autonomic changes [increased heart rate (HR) and decreased HR variability) during both acute stressors and increased anxiety behaviors in the EPM. Oxytocin injection prevented the autonomic consequences of the acute stressors in isolated prairie voles, but did not affect the behaviors tested under the present conditions. Oxytocin had no effect on the behavioral or autonomic responsiveness in paired prairie voles. Oxytocin injection may exert a beneficial effect on autonomic responses to stressors in isolated animals through increasing the number of oxytocin-containing neurons and decreasing the number of corticotropin-releasing hormone-containing neurons in the PVN. Oxytocinergic mechanisms may serve to compensate for autonomic responses associated with chronic isolation and exposure to both social and non-social acute stressors.     

The effect of interpolated activity on a treble right-left alternation task

In a delayed treble alternation task the number of errors made by human subjects was found to increase when an irrelevant task was presented in the delay interval. The number of errors increased with the number of items presented in the delay interval, but neither the difficulty of the irrelevant task nor its similarity to the alternation task was found to affect the number of errors.     

Fear reduction in rats through avoidance blocking

Rats trained to avoid an electric shock in an alley were divided into two groups depending on their behavior during 25 min of response blocking. Subjects demonstrating exploratory behavior while blocked were put in one group, while subjects demonstrating agitation, freezing or grooming were placed in another. Fear measures, when subsequently exposed to the CS. were taken on experimental subjects and compared to controls. The results confirmed the hypothesis that response blocking can lead to fear reduction and that the fear reduction is related to the behavior of the subject during blocking.