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Chicks' maze learning reinforced by visual pitfall extending downward.

The present study examined whether visually evoked fear of depth could reinforce a particular response of animals, i.e., to special maze learning. The maze was composed of four units of Y-shaped alley. In this maze, the visual pitfalls were set behind corners of the alley in place of a physical barrier. The experiments showed that eight of 13 male chicks could achieve the initial learning and that three successful ones could also achieve reversal learning. The results suggest that the visually evoked fear of depth provided by motion parallax can act as a reinforcer.

Animals↗

GABA and muscimol as reversible inactivation tools in learning and memory.

Reversible inactivation of brain areas is a useful method for inferring brain-behavior relationships. Infusion of GABA or of the GABA receptor agonist muscimol is considered one interesting reversible inactivation method because it may not affect fibers of passage and may therefore be compared to axon-sparing types of lesions. This article reviews the data obtained with this method in learning and memory experiments. A critical analysis of data, collected in collaboration with Simon Brailowsky, with chronic GABA infusion is presented, together with an illustration of data obtained with muscimol-induced inactivation.

Animals↗

Learning impairments induced by glutamate blockade using dizocilpine (MK-801) in monkeys.

1. This study investigated the effects of dizocilpine (MK-801) on learning ability in a non-human primate. Acquisition and reversal learning of visual discrimination tasks and acquisition of visuo-spatial discrimination tasks were assessed in marmosets using the Wisconsin General Test Apparatus. Dizocilpine impaired acquisition of visuo-spatial (conditional) tasks requiring spatial responses to coloured objects, and perceptually difficult visual discrimination tasks in which stimulus objects are painted black. Dizocilpine did not, however, impair either acquisition or reversal of a simple visual discrimination task using easily discriminated, coloured objects. 2. Motor effects of dizocilpine treatment, which have been seen in other primates, were examined by observation of the marmosets in their home cages, using both an automated locomotor activity monitor and 'blind', subjective counting of the number of abnormal movements in a given time period. Locomotor activity, assessed using the automated monitor, was not significantly affected at any of the doses tested. Incoordination, assessed by human observation of abnormal movements, was significantly increased only at a dose of 30 microg kg(-1) i.m., which was twice the highest dose used to assess the effects of dizocilpine on cognition. 3. We have, therefore, found an effect of dizocilpine on acquisition and reversal of some types of cognitive task, at a dose which does not cause significant motor effects. This demonstration of a cognitive deficit associated with glutamatergic blockade in a primate may be useful in understanding the contribution of glutamatergic dysfunction to cognitive decline in neurodegenerative disease, especially Alzheimer's disease.

Animals↗

Spatial and visual learning deficits in Alzheimer's and Parkinson's disease.

Experimental paradigms adopted from animal models were used to compare the neuropsychological mechanisms underlying the dementias of Alzheimer's and Parkinson's diseases. Two tasks were selected because characteristic profiles of impairment in nonhuman primates are seen following selective lesions of frontal cortex, temporal cortex, and fornix. The tasks consisted of a spatial and a visual learning problem, each with two components: (1) original learning and (2) reversal of the original learning. The Alzheimer's patients were significantly impaired on original learning and reversal learning in the visual modality compared with demented Parkinson's patients, even though both groups were equated for severity of dementia. On the spatial tasks, both the Alzheimer's and the demented Parkinson's patients were impaired on reversal learning but not on original learning. The profile of deficits on the visual tasks may serve to differentiate Alzheimer's from Parkinson's dementia and may reflect selective orbitofrontal system lesions in the former.

Aged↗

Learning and memory in rats gestationally and lactationally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Recently we reported that in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or coplanar polychlorinated biphenyls (PCBs) resulted in a reduction of errors on a radial arm maze (RAM) working memory task. The effect was more pronounced in males than in females. In this study, we further investigated the effects of in utero and lactational exposure to TCDD on learning and memory by testing male and female TCDD-exposed rats on three different spatial learning and memory tasks: the RAM, the Morris water maze (MWM), and spatial discrimination-reversal learning (RL), as well as on a nonspatial learning task, visual RL. Time-mated Sprague-Dawley rats were gavaged with either TCDD (0.1 microg/kg/day) or corn oil vehicle on gestation days 10-16. Litters were culled to eight on day 2 and weaned on day 21. Beginning on day 80, one male and one female from each litter were tested on the same RAM working memory task used in the previous study. Again, the TCDD-exposed male rats displayed a pronounced decrease in errors relative to control males. Following the RAM testing, the same animals were tested on the MWM, but no differences between the exposed and control rats were observed. Another male and female from each litter were tested on spatial RL on a T-maze. There were no differences between the exposed and control rats on this task. Following spatial RL, the same rats were tested on visual RL on the same maze. The exposed animals did not differ from controls on original learning, but took more trials to reach criterion on the first and second reversals. These results demonstrate a reliable, but task-specific, facilitation of spatial learning and memory in male rats exposed to TCDD during gestation and lactation. In contrast, both male and female TCDD-exposed rats showed a deficit in learning on the visual RL task. This pattern is consistent with that seen in earlier monkey studies. Perinatally TCDD-exposed monkeys were facilitated on certain spatial tasks, but impaired on visual RL tasks.

Analysis of Variance↗

Complexin II is essential for normal neurological function in mice.

Complexins (CPLXs) are modulators of synaptic vesicle release. At 1 year of age, CPLXII knockout (KO) mice appear normal. However, behavioral testing reveals underlying deficits of motor and cognitive function in these mice. We found motor deficits on the rotarod, and learning deficits in the Morris water maze (both acquisition and reversal) and the two-choice swim tank (reversal). The reversal learning deficits are particularly noticeable, being present from the earliest time of testing, when most other behaviors are normal. CPLXII KO mice also fail to develop adult patterns of exploratory behavior in the open field and show deficits in interactive grooming behaviors. The behavioral deficits worsen with age. For example, while rotarod performance is normal until 10 weeks, it is impaired from 24 weeks onwards. Similarly, deficits in spatial learning in the Morris water maze are mild at 8 weeks, but pronounced by 1 year of age. The deficits seen in CPLXII KO mice are not due to physical weakness, since their ability to run, swim and grip is unimpaired. Rather, the mice appear to have deficits of higher function. The deficits seen in CPLXII KO mice are strikingly similar to those seen in the R6/2 model of Huntington's disease (HD) where a progressive depletion of CPLXII is seen. This suggests that depletion of CPLXII contributes to cognitive abnormalities in R6/2 mice. Given that decreased expression of CPLXII is seen in HD and schizophrenic patients, a role for CPLXII depletion should be considered in other diseases where motor, cognitive and psychiatric symptoms co-exist.

Adaptor Proteins, Vesicular Transport↗

Limbic seizures, but not kindling, reversibly impair place learning in the Morris water maze.

We investigated the effects of kindling and kindled seizures in different limbic structures on place and cue learning in the Morris water maze. The triggering of seizures by stimulation of the perforant path, septum, or amygdala prior to daily training impaired place learning, but had little effect on visible platform training or swim speed. Seizures triggered by stimulation of the medial perforant path after daily training also impaired place learning. Conversely, place learning proceeded normally in rats tested 24 h after kindling triggered by stimulation of the perforant path, septum, or amygdala, indicating that kindling per se does not affect place learning. Each group was able to learn the location of a reversed platform when pretraining seizures were discontinued; and perforant path and septal kindled rats, but not amygdaloid kindled rats, were impaired at learning the location of a reversed platform when seizures were triggered before training. The results confirm previous reports that limbic seizures produce amnesia, but they contradict the finding that hippocampal kindling impairs learning on tasks sensitive to hippocampal lesions.

Amygdala↗

Extracellular level of basolateral amygdalar dopamine responding to reversal of appetitive-conditioned discrimination in young and old rats.

Young and old rats, aged 3 and 24 months old, respectively, were conditioned to press a lever under lamp-on conditions for reward acquisition and lamp-off for no reward using a variable interval reinforcement schedule that averaged 15 s; i.e., the minimal requirement was 4 responses/min. Over a 30-day period, young and old groups showed increased response to lamp-on from 22 to 35/min and from 10 to 23/min, respectively, and shortened response to lamp-off after initial training. Response to lamp-on as a percentage of total response to lamp-on and -off (the discrimination ratio) was over 80%. For the next 30 days, reversal learning was imposed to reinforce discrimination of the lamp-off state. Young rats showed a steadily increasing discrimination ratio from 40% to 70%, and old rats from 30% to 60%. In comparison with the initial training, young rats showed a total response increase from 50% to 60%, while old rats showed an approximately 5% decrease without loss of reward-obtaining efficiency. In vivo microdialysis during reversal revealed that young rats had higher dopamine transmission in the basolateral amygdala than old rats. The dopamine level was positively correlated with the number of responses to state of reward in young rats and negatively with the numbers of both NRF and RF responses to lamp-on and -off states in old rats. These results suggest that in reversal discrimination, basolateral amygdalar dopamine efflux correlates with the manner of age-related conditioned response rather than the ability to learn.

Age Factors↗

A tuna fish diet influences cat behavior.

When observed in their home cages, cats fed commercial tuna fish cat food were less active, vocalized less, and spent more time on the floor and more time eating than cats fed commercial beef cat food. There were no differences in response to human handling between the two groups. There were no differences in learning ability on a two-choice point maze or in reversal learning in the same maze between beef- and tuna-fed cats. The behavior of the groups differed in a 15-min open field test only in the number of toys contacted. Cats fed the tuna had elevated tissue levels of mercury and selenium.

Animal Feed↗

Neonatal exposure to a high level of ACTH4-10 impairs adult learning performance.

Male offspring of Sprague-Dawley dams were injected with 25 micrograms of ACTH4-10 or the vehicle on days 2 through 7 postpartum. Peptide treated animals exhibited a marked motor response to the peptide injection. Adrenal weights of these animals were consistently heavier than littermate controls in both the developing and adult animals. ACTH4-10 treated neonates exhibited significantly poorer learning performance in the shuttle box and were slower to acquire the reversal learning problem of a visual discrimination task under light shock levels. In addition, these animals also exhibited an exaggerated startle response and a stronger thigmotaxis response in the open field than controls. These results indicate that exposing the developing nervous system to relatively high levels of ACTH4-10 can produce marked long-term effects on behavior.

Acoustic Stimulation↗

Smells are no surer: rapid improvement in olfactory discrimination is not due to the acquisition of a learning set.

The claim that rats can demonstrate the 'primate-like' learning capacity of learning set formation when trained with olfactory cues, rather than visual or auditory cues, has generated considerable interest in recent years. In this study, the claim is evaluated in detail by using a series of experimental and control procedures to determine whether rats do indeed develop the abstract 'win-stay, lose-shift' strategy which underlies learning set formation in monkeys. We report here that although exposure to a series of novel olfactory discrimination problems gives rise to progressive improvement in the rate of learning, it is not a necessary condition for the development of that rapid learning. Furthermore, even rats which fail to display progressive improvement in olfactory reversal learning show rapid learning on novel olfactory discrimination problems. Each of these findings suggests that although olfactory learning may be rapid, learning set formation does not occur over a short series of problems.

Animals↗

Superior water maze performance and increase in fear-related behavior in the endothelial nitric oxide synthase-deficient mouse together with monoamine changes in cerebellum and ventral striatum.

Nitric oxide (NO) has been implicated in the control of emotion, learning, and memory. We have examined endothelial NO synthase-deficient mice (eNOS-/-) in terms of habituation to an open field, elevated plus-maze behavior, Morris water maze performance, and changes in cerebral monoamines. In the open field, eNOS-/- animals were less active than wild-type controls but showed unimpaired habituation. In the plus-maze, an anxiogenic effect was observed. Proceeding from previous findings of deficits in hippocampal and neocortical long-term potentiation (LTP) in our eNOS-/- mice, we investigated whether these animals also express deficits in learning tasks that have been linked to hippocampal function and LTP. Unexpectedly, eNOS gene disruption led to accelerated place learning in the water maze. Furthermore, during long-term retention and reversal learning, eNOS-/- mice showed improved performance. In a cued version of the water maze task, eNOS-/- and control mice did not differ, implying that the superior performance of eNOS-/- animals on the former tasks cannot be attributed solely to differences in sensorimotor capacities. The neurochemical evaluation of the eNOS-/- mice revealed increases in the concentrations of the serotonin metabolite 5-HIAA in the cerebellum, together with an accelerated serotonin turnover in the frontal cortex. Furthermore, eNOS-/- mice had a higher dopamine turnover in the ventral striatum. These findings are discussed in terms of possible concomitant effects on physiological parameters, such as a decreased reactivity of GABAergic neurotransmission or changes in vascular functions, and effects on behavioral processes related to reinforcement, learning, and emotion.

3,4-Dihydroxyphenylacetic Acid↗

Glutamate receptor binding in the frontal cortex and dorsal striatum of aged rats with impaired attentional set-shifting.

Aged Long-Evans rats exhibit deficits in attentional set shifting, an aspect of executive function, relative to adult rats. Impairments in set shifting and spatial learning are uncorrelated in aged rats, indicating a possible dissociation of the effects of ageing in prefrontal versus hippocampal systems. Ionotropic glutamate receptor binding was assessed using an in vitro autoradiography method in young and aged rats. The rats had been tested on a set-shifting task that measured attentional set shifts and reversal learning, as well as in a spatial learning task in the Morris water maze. [3H]Kainate, [3H]AMPA and NMDA-displaceable [3H]glutamate receptor binding were quantified in orbital cortex, cingulate cortex, medial frontal cortex, dorsolateral and dorsomedial striatum. Age-related decreases in [3H]kainate binding were apparent in all regions measured. Similarly, NMDA-displaceable [3H]glutamate binding was decreased in the aged rats in all the regions measured except for the medial frontal area where no age effects were observed. [3H]AMPA receptor binding was preserved with age in all the regions measured. Lower levels of [3H]kainate binding in the cingulate cortex were significantly correlated with poorer set-shifting performance, whereas higher levels of NMDA binding in the dorsomedial striatum were correlated with poorer set-shifting performance. There were no significant correlations between the levels of ionotropic glutamate receptors and performance in the reversal task or spatial learning in the Morris water maze. These results indicate that age-related behavioural deficits in attentional set shifting are selectively associated with neurobiological alterations in the cingulate cortex and dorsomedial striatum.

Aging↗

Neonatal Frontal Lesions in the rat: sparing of learned but not species-typical behavior in the presence of reduced brain weight and cortical thickness.

Rats with complete removal of the cortex anterior to bregma in adulthood (frontal cortex) were compared behaviorally and neuroanatomically with rats with similar removals at 7 or 25 days of age. Excision of the frontal cortex in adult rats produced transient aphagia, chronic motor abnormalities in feeding, a chronic drop in body weight, increased activity in running wheels, impaired performance at a spatial reversal learning task, and chronic abnormalities in a variety of species-typical behaviors, including swimming, food hoarding, and defensive burying. In contrast, similar lesions in infant rats failed to produce aphagia, a chronic drop in body weight, increased activity, or impaired learning of a spatial reversal task. Infant lesions did not allow sparing of complex species-typical behaviors, however, such as those involved in feeding, swimming, hoarding, or defensive burying. Furthermore, when the brains of neonatally operated rats were compared with those of control rats or rats operated on in adulthood, there were striking differences. The cerebral hemispheres of the neonatal operates were smaller both in surface dimensions and weight, the thalamus was smaller, and the cerebral cortex was thinner. These data imply that there may be substantially less sparing of function following frontal cortex lesions in infancy than previously believed and that neonatal frontal lesions in rats have significant effects on brain development in regions far removed from the actual site of surgical excision.

Aging↗

Differential effects of inescapable shock on escape performance and discrimination learning in a water escape task.

The effects of inescapable shock on subsequent T-maze water escape and position discrimination performance were evaluated in seven experiments. Escapable shock did not disrupt water escape performance; however, escape performance was retarded 24 hr after inescapable shock. These deficits were not apparent if escape was possible upon stress inception; however, pronounced deficits were noted if sustained active responding was necessitated by briefly (3-5 sec) preventing escape. When water escape testing was conducted in relatively warm water (20 degrees C), the disruptive effects of preshock were not apparent. In colder water (15 degrees C), which increases the motor difficulty of the task, the disruptive effects of preshock were noted. When the motor difficulty of the task was increased further, by testing mice in 10 degrees C water, or when the associative difficulty was increased by using a vigorous reversal learning task, the differences between the preshocked and nonpreshocked groups were obviated. Exposure to inescapable shock did not disrupt position discrimination performance regardless of the motor difficulties of the task. Similarly, deficits of discrimination performance were not apparant in mice exposed to inescapable shock even when the associative difficulty of the task was increased by removing intramaze cues or by testing animals in a position discrimination reversal task. It is concluded that inescapable shock results in deficits of response maintenance but probably has a minor, if any, influence on cognitive/associative processes.

Animals↗

Cognitive effects of Colostral-Val nonapeptide in aged rats.

Colostrinin, a complex of polypeptides derived from sheep colostrum retards the progress of Alzheimer's disease and facilitates acquisition and retrieval of spatial memory in aged rats. Here we investigated the cognitive effects of colostrinin-derived nonapeptide (Colostral-Val nonapeptide, CVNP) in aged rats that demonstrated learning deficits. Administered for 14 days, CVNP did not affect the acquisition of spatial learning or memory retrieval in the Morris water maze. As a result of reversal learning, placebo treated rats shifted searching behavior and swam less in the area of original platform position and more in the area of recent platform position, suggesting formation of the new spatial map. CVNP treated rats did not change the searching pattern and still investigated the area that contained "original" escape platform, suggesting that CVNP treatment delays the extinction of spatial memory. In another experiment, CVNP administered for 8 days did not influence the acquisition of the active avoidance task, but significantly delayed its extinction. The present findings indicate that colostrinin-derived nonapeptide may delay the extinction of long-term memories.

Aging↗

Responses of cells in the tail of the caudate nucleus during visual discrimination learning.

1. The tail of the caudate nucleus and adjacent ventral putamen (ventrocaudal neostriatum) are major projection sites of the extrastriate visual cortex. Visual information is then relayed, directly or indirectly, to a variety of structures with motor functions. To test for a role of the ventrocaudal neostriatum in stimulus-response association learning, or habit formation, neuronal responses were recorded while monkeys performed a visual discrimination task. Additional data were collected from cells in cortical area TF, which serve as a comparison and control for the caudate data. 2. Two monkeys were trained to perform an asymmetrically reinforced go-no go visual discrimination. The stimuli were complex colored patterns, randomly assigned to be either positive or negative. The monkey was rewarded with juice for releasing a bar when a positive stimulus was presented, whereas a negative stimulus signaled that no reward was available and that the monkey should withhold its response. Neuronal responses were recorded both while the monkey performed the task with previously learned stimuli and while it learned the task with new stimuli. In some cases, responses were recorded during reversal learning. 3. There was no evidence that cells in the ventrocaudal neostriatum were influenced by the reward contingencies of the task. Cells did not fire preferentially to the onset of either positive or negative stimuli; neither did cells fire in response to the reward itself or in association with the motor response of the monkey. Only visual responses were apparent. 4. The visual properties of cells in these structures resembled those of cells in some of the cortical areas projecting to them. Most cells responded selectively to different visual stimuli. The degree of stimulus selectivity was assessed with discriminant analysis and was found to be quantitatively similar to that of inferior temporal cells tested with similar stimuli. Likewise, like inferior temporal cells, many cells in the ventrocaudal neostriatum had large, bilateral receptive fields. Some cells had "doughnut"-shaped receptive fields, with stronger responses in the periphery of both visual fields than at the fovea, similar to the fields of some cells in the superior temporal polysensory area. Although the absence of task-specific responses argues that ventrocaudal neostriatal cells are not themselves the mediators of visual learning in the task employed, their cortical-like visual properties suggest that they might relay visual information important for visuomotor plasticity in other structures. (ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Goal directed motor behavior and its adaptation following reversed tactile perception in man.

When two adjacent fingers are crossed over each other and two tactile stimuli are touched to the two crossed fingertips, the two stimuli are perceived to be inverted in space. This phenomenon of tactile reversal was used in the present work to study the sensorimotor transformation occurring in goal directed motor behavior. When the subjects had to perform a movement toward a tactile stimulus (target) in tactile reversal conditions, the stimulus directed movements were performed wrongly, that is, away from the target. However, not all the subjects perceived a complete inversion of the stimuli; in this case, the target stimulus was perceived to be on the same side as its actual position, although with an error. In these conditions, the stimulus directed movements were performed correctly, that is, toward the target. These results show that the illusory spatial perception of the stimuli controls motor behavior on the basis of the amount of the perceptual error. Within the first hour of training, several compensatory responses occurred so as to produce correct motor performance. Despite this motor learning, reversed tactile perception remained reversed. Therefore, what subjects learned was the execution of the movements opposite to those necessary for reaching the target stimulus, without any change in perception. In the context of theories concerning the relationship between motor learning and perceptual adaptation, the present study shows that, with this experimental paradigm, motor learning during the first hour was mainly cognitive and did not have short-term effects upon perceptual processes.

Adaptation, Psychological↗