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Basolateral amygdala lesions block glucocorticoid-induced modulation of memory for spatial learning.

This study examined the role of the amygdala in mediating the effects of glucocorticoids on spatial memory in rats. Adrenalectomy (ADX) induced 4-5 days prior to training impaired memory in a water-maze spatial task. This effect was reversed by a posttraining injection of dexamethasone (0.3 mg/kg sc) but not by corticosterone (0.3 mg/kg). Lesions of the basolateral (BLA), but not the central (CEA) or the medial (MEA), amygdala blocked the effects of ADX and dexamethasone. ADX also impaired acquisition. CEA, MEA, and BLA lesions blocked the ADX effect on acquisition. In adrenally intact rats, intracerebroventricular posttraining injections of a specific glucocorticoid receptor (GR or Type-II) antagonist impaired retention, and BLA lesions blocked the effect of the GR antagonist. These findings provide evidence that the BLA is involved in mediating glucocorticoid influences on learning and memory.

Adrenalectomy

Reversible inactivation of the lateral dorsal thalamus disrupts hippocampal place representation and impairs spatial learning.

Place-specific discharge of hippocampal cells was monitored while rats performed daily 15 trials of a spatial memory task. During the intertrial interval between trials 5 and 6, the lateral dorsal nucleus of the thalamus (LDN) was reversibly inactivated. Choice accuracy on the maze became impaired, and many hippocampal place fields became disrupted. These data support the proposition that the LDN passes onto hippocampus important (spatial) information that is used for accurate maze navigation.

Animals

Spatial learning disabilities and underachievement among university anatomy students.

In this study the relationship between underachievement in anatomy and spatial ability (both geometrical and anatomical) is investigated. Subjects were second-year medical students at the University of Cape Town from 1980 to 1983. Geometrical spatial ability was measured using a battery of three-dimensional exercises involving the sectioning, joining, translation, rotation and visualization of simple solid objects. Anatomical spatial achievement was measured using university practical examination scores of April, June and October, as well as students' scores on those items in the April, June and November MCQ anatomy examinations which were classified as spatially three-dimensional by a panel of lecturers in anatomy. Non-spatial anatomical achievement was measured using the university essay examination scores of April, June and November, together with students' scores on the non-spatial items in the MCQ anatomy examinations. From 1980 to 1983 it was found that students who failed the battery of geometrical spatial exercises and/or recorded large, persistent deficits on spatial MCQs relative to non-spatial MCQs, scored significantly lower marks in practical anatomy examinations throughout the year than those students who scored well in the battery of geometrical spatial exercises. Spatially competent and spatially inept students performed equally well on the non-spatial MCQs and the non-spatial essay examinations. Borderline and failing students recorded the greatest deficits in anatomical spatial scores (for whom losses of approximately 18% occurred in practical examinations in anatomy). Since potential failures with persistent spatial handicaps can be readily identified by mid-year, a programme of differentiated teaching methods is recommended for these students.

Achievement

Learning spatial dimensions with a visual sensory aid: Molyneux revisited.

The relationship between sensory aid research and several areas of perceptual learning has been explored with five experiments on learning the use of the Binaural Sensory Aid, an electronic sensor in which pitch specifies distance and interaural amplitude difference (IAD) specifies direction. The training task required reaching to objects in near space, with tactile error feedback. Perceptual learning for both dimensions was demonstrated within 72 trials, giving a level of performance comparable to the use of a natural sound source, although performance with the direction cue did not reach asymptote until a second training session. Training was unaffected by various kinds of regularity in the spatial target sequences, or by a reduction in the number of spatial target locations until only two locations were used; at this point directional accuracy declines. Training only one dimension at a time did not produce additional improvement of performance on that dimension, but did impair generalization of the direction cue. Learning of the pitch-distance dimension was generally better than that of the IAD dimension, possibly because of its greater discriminability with this device. Generally, the pattern of results indicates that in learning to use such devices subjects readily determine the sensory dimensions of the codes and have considerable ability to generalize to new locations.

Distance Perception

The effect of electroconvulsive shock and nifedipine on spatial learning and memory in rats.

Several traumatic events including brain contusion, electroconvulsive shock therapy, epileptic seizures and others, may cause short-term retrograde amnesia. In spite of much recent attention, pharmacological treatment of memory impairment has not been fully successful. In the present paper we report on the possible antiamnesic action of the L-type calcium channel blocker, nifedipine. Rats trained in the spatial memory task showed gradual improvement in the escape latency to find the submerged platform. After completion of the learning, they also showed a strong spatial bias toward the place that previously contained the target platform. Prolonged post-trial electroconvulsive shock induced memory impairment. The calcium channel blocker, previously reported as a "cognitive enhancer," given either before or after the learning trial revealed no antiamnesic effect. Nifedipine also does not exert any action when given alone. These results suggest that the drug may not have antiamnesic action on human memory disturbed by electroconvulsive therapy.

Animals

Naloxone facilitates spatial learning in a water-maze task in female, but not male, adult nonbreeding meadow voles.

The present study examined the effects of the opiate antagonist naloxone on spatial acquisition and retention in a water-maze task by adult, nonbreeding, male and female meadow voles (Microtus pennsylvanicus). Voles were required to learn the position of a hidden, submerged platform using distal visual cues. There were four trials per day for 6 days. Daily pretraining (15 min before first trial) systemic administrations of naloxone (1.0 mg/kg, IP) significantly facilitated spatial acquisition in female, but not in male, voles in a water-maze task on days 2, 3, and 4. There were two probe tasks given 1 day and 1 week after the last training trial. All groups acquired the spatial task by the end of the fifth day with no significant effects of naloxone on retention of the spatial task. There were also no significant sex differences in acquisition of the spatial task and task retention in control, nonbreeding adult voles. It is suggested that the lack of sex differences in basal spatial performance may be related to the low levels of testosterone in male nonbreeding voles. The obtained sex differences in the effects of naloxone on spatial acquisition are considered in relation to sex differences in stress, opiate responses, and gonadal steroid levels.

Animals

Rotational stimulation disrupts spatial learning in fornix-lesioned rats.

Normal and fornix-lesioned rats were trained to find water in a version of a spatial discrimination task involving the use of a cross maze modified for interspersing rotational stimulation before the start of each trial. The central (cross) portion of the maze rested on a turntable and consisted of a covered start box opening into the intersection of the cross, allowing choice among three covered alleys, each of which led through a black curtain onto a stationary goal arm. The animal could be started in one of three positions (0 degree, 90 degrees, 270 degrees) in relation to the rewarded goal arm. Room cues were not available until after the animal made the choice in the covered tunnel area. A 20-day testing period in which one to ten full revolutions were interspersed before the start of each trial revealed marked differences between normal and fornix-lesioned animals. The overall performance of normal animals improved from 40% correct choices to 85% correct during the testing period. Fornix-lesioned rats showed no significant improvement during the same period. Performance on probe trials in which room cues were made available to the animals during interspersed rotations improved rapidly and was not significantly different between the two groups. The results suggest that adaptation to vestibular system stimulation was required to solve the covered tunnel task in normal rats and that such processes were disrupted in fornix-lesioned rats.

Animals

Enhanced detection of nucleus basalis magnocellularis lesion-induced spatial learning deficit in rats by modification of training regimen.

Bilateral excitotoxic lesions of the nucleus basalis magnocellularis (NBM) in the rat cause deficits in the water maze, a spatial memory paradigm. Previous investigations aimed at reversing the water maze performance deficit with anticholinesterase treatments have been unable to demonstrate a consistent drug effect due to the relatively good acquisition of the task seen following NBM lesions. The present investigation tested three different water maze training regimens designed to separate the learning curves. F-344 rats received bilateral NBM injections of ibotenic acid; sham-operated rats served as controls. The animals were tested in three groups in the water maze as follows: (1) four trials per day with no intertrial interval (standard paradigm), (2) four trials per day with a 10-minute intertrial interval, and (3) two trials per day with no intertrial interval. Each group was tested in the water maze for five consecutive days, followed by two days of rest, and then tested for an additional five days. The two-trial per day paradigm was more difficult than the standard paradigm for both lesions and controls and yielded the most difference between lesions and controls as compared to the other two testing regimens. The 10-min intertrial interval schedule was more difficult than the standard paradigm for lesioned animals but acquisition was not affected in control rats. These data demonstrate that the nucleus basalis lesions cause a deficit in the water maze task regardless of training parameters. Further, while all rats showed some acquisition of the water maze task, training schedule affected the level of learning of both lesioned and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The effects of undernutrition during early life on spatial learning.

Recent research has shown that a lengthy period of undernutrition during early postnatal life can cause alterations in the morphological structure of the dentate gyrus. As this region is involved in the control of spatial memory, we decided to investigate whether undernourished rats also showed any deficits in this aspect of behaviour. Rats were undernourished from about birth until either 30 or 60 days of age and then nutritionally rehabilitated for a lengthy period before testing. There were significant differences in the body weight of control and undernourished rats in each experiment. The testing procedure involved rats being placed in a large pool of opaque water. They were required to swim to find a hidden platform located just below the water surface onto which they could escape. Each rat had to perform this test 20 times over a period of 3 days. The time taken and the total distance swum by each rat during each trial was measured. In Experiment 1, rats were familiarised with the water before testing took place, whereas in Experiment 2 they were not. There were no significant differences in the latency to find the platform or the distance swum between well-fed control and previously undernourished rats in either experiment. In conclusion, in our experiments we could not demonstrate that undernutrition during early life caused any deficits in spatial memory performance.

Animals

Phencyclidine injections into the dorsal hippocampus disrupt long- but not short-term memory within a spatial learning task.

Since the hippocampus is likely to be a major site of phencyclidine (PCP) action, the effects of various doses of PCP (1.8, 18 or 36 nM) as well as 3.6 nM MK-801 or saline injected directly into the dentate gyrus of the hippocampus was tested for acquisition of a spatial navigation task (dry land version of a water maze) using a paradigm that assesses short term memory based on learning within a day and long term memory based on learning between days. Results indicated that relative to saline or 1.8 nM PCP injected rats, rats with 18 or 36 nM PCP or 3.6 nM MK-801 injections were impaired in acquisition of the task as measured by increased distances traveled to find the food location between days but not within days. In additional experiments 36 nM PCP or 3.6 nM MK-801 did not produce any deficits in the acquisition of an object discrimination task. It is suggested that PCP through its blocking action of the NMDA receptor in the dentate gyrus or CA1 region of the dorsal hippocampus mediates the consolidation of new spatial location information.

Animals

Cortical noradrenaline depletion eliminates sparing of spatial learning after neonatal frontal cortex damage in the rat.

The possibility that cortical noradrenaline (NA) is necessary for the sparing of function that occurs after neonatal frontal cortex damage was examined. Spatial localization by rats with frontal cortex damage sustained neonatally was better than by rats with similar damage sustained as adults. The sparing was abolished in rats depleted of cortical noradrenaline by means of neonatal 6-hydroxydopamine (6-OHDA) administration. NA depletion alone did not affect spatial localization. These data are consistent with the notion that NA has some general function in maintaining some forms of plasticity in posterior cortex.

Animals

Protein kinase C activity in the hippocampus following spatial learning tasks in mice.

Protein kinase C (PKC) is highly concentrated in the hippocampus and is thus a possible neural substrate of learning and memory. This study was designed to determine whether partial acquisition (i.e., the minimal amount of training leading to above-chance performance) of a spatial discrimination in an eight-arm radial maze alters hippocampal PKC activity. Mice were sacrificed at different times (5 minutes, 1 hour, 24 hours) after the second learning session, and PKC activity was measured in both cytosolic and membrane fractions of the hippocampus. In order to determine which component of the task was involved in the alterations in enzymatic activity, hippocampal PKC activity was also measured in a group of mice that was allowed to explore the maze freely. Significantly less PKC activity was found in the cytosolic fraction from the trained animals than from the quiet or active control groups. No differences were observed between the quiet and active controls. In contrast, there were no significant between-groups differences in membrane-bound PKC activity, although a negative correlation between the membrane-bound PKC activity and learning scores (accuracy) was noted. These results suggest that hippocampal PKC activity is involved essentially in the associative component of the task. The lack of learning-induced alterations in membrane-bound PKC activity and the negative correlation between this enzymatic activity and learning accuracy are discussed.

Animals

Enhanced disruptive spatial learning effect after sufentanil in renal hypertensive rats versus normotensive rats.

The effects of the peripherally administered sufentanil citrate (S), a potent opioid agonist with high affinity for mu receptors on the spatial navigation task, were tested in normotensive Wistar (NR) and renal hypertensive rats (RHR). Rats were injected subcutaneously once daily in doses of 0.25 or 1 microgram/kg S before the water maze training. In NR rats, weak effects of 0.25 micrograms/kg S and impairments after 1 microgram/kg S were seen, whereas in RHR 0.25 and 1 microgram/kg S showed clearcut impairments. These data from the Morris water maze task support previous reports that RHR have an increased sensitivity for opioid agonists.

Animals

Hippocampal synaptic enhancement and spatial learning in the Morris swim task.

The authors attempted to replicate the study of Castro, Silbert, McNaughton, and Barnes (1989) in which it was concluded that bilateral saturation of hippocampal synaptic enhancement produced a deficit in acquisition of a spatial navigation problem in the Morris swim task. The original protocol was followed as closely as possible, but no effect of long-term enhancement (LTE) saturation on spatial performance in this task was found. This negative result suggests either that the previous finding using the swim task reflected statistical error or that some as yet undetermined variable is of critical importance in this phenomenon. The present negative finding also raises a question concerning the reproducibility of the earlier results of McNaughton, Barnes, Rao, Baldwin, and Rasmussen (1986) in which LTE saturation apparently led to a prolonged deficit on a different spatial task. Although negative results in such experiments do not constitute grounds for rejecting the underlying hypothesis, the present lack of a positive effect renders uncertain, for the time being, one of the lines of experimental support for the theory that LTE at hippocampal synapses reflects a mechanism for the associative, distributed storage of new spatial information.

Animals

D-cycloserine reverses the working memory impairment of hippocampal-lesioned rats in a spatial learning task.

It is shown that D-cycloserine has cognition-enhancing properties in quinolinic acid hippocampal-lesioned rats. Lesioned rats had a severe impairment of working memory in an allocentric spatial reversal paradigm in the 8-arm maze, and performance could be restored with 12 mg/kg i.p. D-cycloserine, given 30 min before testing. The present findings favour the testing of D-cycloserine for clinical efficacy in patients with Alzheimer's disease with loss of pyramidal neurons and disconnected glycine-NMDA receptor activation.

Analysis of Variance

Spatial learning deficit and reduced hippocampal ChAT activity in rats after an ICV injection of streptozotocin.

ICV injections of streptozotocin (STREP) lower the glucose utilization of the brain and affect the cholinergic system. The present study was designed to evaluate whether STREP-treated rats have an impaired spatial discrimination performance in the Morris spatial navigation task. Performance in this task is sensitive to treatment with cholinergic antagonists. In contrast to young rats, middle-aged STREP-treated rats tended to have an impaired spatial discrimination performance in the Morris task at the end of training. In middle-aged STREP-treated rats, but not in control rats, spatial discrimination performance was associated with hippocampal choline acetyltransferase (ChAT) activity. The correlation between spatial discrimination performance in the Morris task and the decrease in hippocampal ChAT activity resembles the relation between cognitive and biochemical changes observed in Alzheimer's disease. Our findings suggest that STREP treatment of middle-aged rats may provide a relevant model for dementia.

Animals

8-Hydroxy-2-(di-n-propylamino)tetralin impairs spatial learning in a water maze: role of postsynaptic 5-HT1A receptors.

1. The effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, on place navigation was studied by use of two spatial tasks in a water maze. 2. In the first experiment, rats treated subcutaneously with 100 and 300 (but not 30) micrograms kg-1 8-OH-DPAT were impaired in their ability to locate a hidden platform. The probe test confirmed the impairment of spatial navigation but the effect (time spent in the training quadrant) was quantitatively different, depending on whether 8-OH-DPAT was administered only before each training session, only before the probe test or in both conditions. 3. In the second experiment, rats received 150 micrograms 5,7-dihydroxytryptamine (5,7-DHT) intracerebroventricularly to destroy 5-hydroxytryptamine (5-HT)-containing neurones and 24 days later were examined for choice accuracy in a two-platform spatial discrimination task. 4. At 100 (but not 30) micrograms kg-1 8-OH-DPAT impaired rats' accuracy with no effect on latency and no errors of omission. In 5,7-DHT-treated rats, this dose had a greater effect, including errors of omission. Sham-operated rats injected with 300 micrograms kg-1 8-OH-DPAT were markedly impaired in accuracy but they had longer latencies and made more errors than controls. All the effects were increased in 5,7-DHT treated rats. 5. The results suggest that, at doses causing no apparent changes in motor behaviour or motivation, 8-OH-DPAT impairs spatial navigation by stimulating postsynaptic 5-HT1A receptors in the rat brain.

5,7-Dihydroxytryptamine