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From movement to transitivity: the role of hippocampal parallel maps in configural learning.

Whether spatial learning is a special case of configural or relational learning, or whether abstract principles evolved from the concrete need to navigate in space, is a question of long-standing debate. The parallel map theory of hippocampal function offers a resolution of the debate by redefining 'spatial learning' as two parallel, geometric processes, Euclidean metric and topological. Moreover, these processes are subserved by independent hippocampal subfields that underlie two ways of representing space, the bearing and the sketch map. It is possible that configural and relational learning, like spatial learning, should also be distinguished in this way. Transitive inference, requiring the construction of a value gradient, could be analyzed as a Euclidean metric problem. In contrast, transverse patterning could be seen as a topological analysis of the relationships among discrete objects. If this interpretation is correct, lesions to the primary bearing map structure (dentate gyrus) should impair transitivity while lesions to the primary sketch map structure (CA1) should impair transverse patterning and similar topological tasks. Recent results from diverse species and tasks lend support to these predictions, suggesting that the hippocampus not only creates parallel maps but uses these maps to solve more abstract configural or relational problems.

Animals↗

Impaired sequential egocentric and allocentric memories in forebrain-specific-NMDA receptor knock-out mice during a new task dissociating strategies of navigation.

The hippocampus is considered to play a role in allocentric but not in egocentric spatial learning. How does this view fit with the emerging evidence that the hippocampus and possibly related cortical areas are necessary for episodic-like memory, i.e., in all situations in which events need to be spatially or sequentially organized? Are NMDA receptor-dependent mechanisms crucial for the acquisition of spatiotemporal relationships? To address this issue, we used knock-out (KO) mice lacking hippocampal CA1 NMDA receptors and presenting a reduction of these receptors in the deep cortical layers (NR1-KO mice). A new task (the starmaze) was designed, allowing us to distinguish allocentric and sequential-egocentric memories. NR1-KO mice were impaired in acquiring both types of memory. Our findings suggest that memories composed of multiple spatiotemporal events require intact NMDA receptors-dependent mechanisms in CA1 and possibly in the deep cortical layers.

Animals↗

Navigation in the Morris swim task as a baseline for drug discrimination: a demonstration with morphine.

A morphine versus saline discrimination was demonstrated using the Morris swim task as the behavioral baseline. The apparatus was a large circular pool filled with water made opaque by floating polypropylene pellets. Rats were placed in the tank in randomly selected locations (12 trials per session) and could escape by swimming to a platform submerged 2 cm below the surface. Morphine (5.6 mg/kg) or saline was injected prior to training sessions. The position of the platform in a given session depended on the drug condition, thus forming the basis for discriminative responding. Three of the 4 rats acquired the discrimination, as evidenced by direct swims to the condition-appropriate platform. Generalization probe sessions were conducted following acquisition. Probe sessions were preceded by injections of morphine (0, 1.0, 3.0, 5.6, or 10.0 mg/kg) and involved placing the rat in the pool for 1 min without a platform. Swim patterns revealed a gradient, with probe swimming more concentrated in the area of the morphine platform position after higher morphine doses. In addition, dose-dependent increases in the likelihood of swimming first to the morphine-associated platform location were obtained. These results illustrate the generality of drug discrimination across different behavioral procedures, and of particular interest with respect to spatial learning, demonstrate interoceptive stimulus control of navigation.

Animals↗

Behavioral teratology of methylmercury.

Behavioral effects of experimental perinatal methylmercury exposure are reviewed. Studies were summarized by classification based on examined behaviors and functions as follows; Development of reflexive behaviors, Swimming ability, Spontaneous activity, Open-field behavior, Maze learning, Avoidance learning, Operant learning, Susceptibility to induced convulsion and seizure, Ultrasonic vocalization, Visual function. Findings suggest that perinatal methylmercury exposure caused changes in a wide spectrum of behaviors in offspring. It is suggested that further researches on neuro-behavioral teratogenicity of methylmercury will be awaited, especially in the area investigating interaction of the other environmental factors.

Animals↗

Conspicuous histomorphological anomalies in the hippocampal formation of rats exposed prenatally to a complex sequenced magnetic field within the nanoTesla range.

The brains of adult rats, exposed prenatally to one of four intensities (between 10 nanoTesla and 1.2 microTesla) of either a frequency-modulated magnetic field or a complex sequenced field designed to affect brain development, were examined histologically. Although from each intensity some rats that had been exposed to the complex sequenced magnetic field showed minor anomalies, those exposed to intensities between 30 nT and 180 nT exhibited conspicuous anomalous organizations of cells within the hippocampal formation. In other studies, rats that had been exposed during their entire prenatal development to the complex sequenced field displayed significantly more activity in the open field and poorer spatial memory during maze learning. Photomicrographs are shown of one conspicuous morphological anomaly within the right hippocampus of an adult rat exposed prenatally to the complex sequenced magnetic field with intensities between .3 mG and .5 mG (30 nT to 50 nT). The results suggest that complex magnetic fields, whose temporal structures approach the time constants of normal biochemical processes, can permanently alter the development of the brain.

Animals↗

Spatial pattern learning in the radial arm maze.

Rats experienced a spatial pattern of baited and unbaited arms in an eight-arm radial maze. The spatial pattern remained constant over trials, but the spatial locations that were baited varied unpredictably. Although there was no evidence of control by the spatial pattern during free choice training trials, the rats' ability to locate baited arms in forced choice test trials was superior to that of animals in a control condition for which maze arms were not baited in a consistent spatial pattern. This is consistent with the results of experiments showing that spatial choices by rats in a pole box maze are controlled by abstract spatial patterns.

Animals↗

Effects of epoetin alfa on cognitive function, mood, asthenia, and quality of life in women with breast cancer undergoing adjuvant chemotherapy.

Several recently published studies describe moderate to severe cognitive dysfunction in breast cancer survivors who were treated with adjuvant chemotherapy 1-5 years before undergoing extensive neuropsychological testing. While these studies are hypothesis-generating and preliminary given their small size and retrospective nature, they consistently suggest that between approximately 15% and 25% of chemotherapy-treated breast cancer patients will have evidence of cognitive dysfunction some years after chemotherapy, compared to about 10% of breast cancer survivors who did not receive chemotherapy. Recent preclinical data strongly suggest that erythropoetin is a potent, endogenous neuroprotective agent that prevents neuronal apoptosis from a variety of insults including hypoxia, trauma, subarachnoidal hemorrhage, and encephalitis. Erythropoietin also appears to enhance learning in a mouse spatial learning maze model. We have conducted a pilot study of epoetin alfa versus placebo in early-stage breast cancer patients who received standard adjuvant anthracycline-based chemotherapy to determine the feasibility of administering standardized neurocognitive assessment tests in the oncology practice setting in order to understand whether the Executive Interview 25 test can detect the subtle cognitive impairment in verbal fluency, attention, and short-term memory observed with chemotherapy, and to assess whether epoetin alfa-treated patients have less evidence of cognitive dysfunction during and 6 months after chemotherapy compared with control-treated patients. We report here the preliminary results of this pilot clinical trial.

Animals↗

[The use of dissociated learning in the study of the mechanisms of memory].

The review is dedicated to description of the phenomenon of dissociated learning. The distinct criteria which discriminate this phenomenon from those similar in appearance are presented. The experimental procedure is described: habituation of an animal, a device for dissociated learning, and the mode of determination of the necessary dose of a drug and injection time. Different versions of dissociated learning which can be gained using the same device, as well as methodical recommendations for researchers in the field of studying this phenomenon. Analysis of the author's data shows that the use of dissociated learning can be promising for studying mechanisms of learning and memory.

Animals↗

The role of ependymin in the development of long lasting synaptic changes.

1.) Three types of training experiments (a complex motor task, avoidance conditioning and classical conditioning) in the goldfish and one in the mouse (T-maze learning) indicate that the brain extracellular glycoprotein (ependymin) has a role in the consolidation process of long-term memory formation. 2.) Direct ELISA measures of the concentration of ependymin in the brain extracellular fluid (ECF) indicate that its level decreases after goldfish learn to associate a light stimulus (cs) with the subsequent arrival of a shock (US): paired CS-US gave changes whereas an unpaired presentation of CS-US gave no changes in comparison to unstimulated controls. 3.) Ependymin is released into ECF and CSF as mixtures of three types of disulfide-linked dimers of two acidic polypeptide chains (M. W. 37 kDa and 31 kDa). It contains 10% carbohydrate as an N-linked glycan. 4.) Ependymin has the capacity to polymerize in response to events that deplete Ca2+ from the brain extracellular environment. A molecular hypothesis relating polymerization properties to the process of formation of long-lasting synaptic changes is proposed. 5.) Investigations of the pattern of regeneration of goldfish optic nerve and the mechanisms of long-term potentiation (LTP) of rat brain hippocampal slices suggest that ependymin has a role in the formation of long-lasting synaptic changes. The E.M. data show that polymerized products which stain with anti-ependymin sera accumulate at synapses and in new spines after LTP.

Animals↗

Irreversible changes in mature and aging animals following intrauterine drug exposure.

Neurobiological and functional changes in mature and aging rodents following intrauterine exposure to tobacco products, amphetamine and the barbiturates are reviewed. The types of behavior surveyed include activity, maze learning, steady state performance, and passive and active avoidance. Hormonal and neurochemical changes are discussed as well. Two opposing hypotheses to account for deficits following fetal drug exposure are presented and evidence for their validity is discussed. One theory states that functional change is nonspecific to the class of drug, whereas the opposing theory is that behavioral change is specific to a drug class.

Abnormalities, Drug-Induced↗

Behavior and neurobehavioral teratology using the ferret.

A behavioral profile of the ferret is presented for those who would like to use this animal in behavioral teratology and toxicology, or other disciplines involving behavior. We have reviewed neurobehavioral teratology of lisencephalic ferrets and neuropsychology of ferrets sustaining frontal lesions, as well as most of the studies of "normal" ferret behavior that have appeared in the research literature. Emphasis is placed on discussion of the tests used and how ferrets behaved on them. The behaviors discussed include spatial (maze) learning, delayed response, visual discrimination learning, discrimination learning sets, schedule maintained behavior, shock avoidance learning and spontaneously occurring behaviors, such as ambulation in open field, spontaneous alternation and species specific behaviors. Although the use of the ferret in behavioral experiments is not yet extensive and large gaps exist in our knowledge about the basic functional capacities of this animal, the ferret is unquestionably well suited for behavioral studies.

Age Factors↗

[Possible mechanisms of the divergent effects of ACTH4--10 and its analog containing the D-isomer of phenylalanine on behavior].

The effect of two oligopeptides--ACTG4-10 and hexopeptide met-glu-his-D-phen-lis-L-phen (Dphen-GP) on memorizing the situation and on orienting-investigating reaction was studied in albino rats by the method of elaboration of food-procuring habit in T-maze and by the method of "open field". It was shown that these peptides in a dose of 15 mcg/kg with certain periods of administration, have an opposite effect on maze learning but a similar effect on memorizing in the "open field". ACTG4-10 slightly increases motor activity in the "open field", whereas Dphen-GP decreases it considerably. It is suggested that ACTG4-10 improves the formation of trace processes independently of the sign of reinforcement, whereas Dphen-GP selectively enhances defensive reaction and memorizing, connected with negative reinforcement.

Adrenocorticotropic Hormone↗

Postnatal development and behavior in offspring of enflurane exposed pregnant rats.

Sperm positive (day zero gestation) Fischer 344 rats were exposed to air or to 1500 ppm enflurane by inhalation for 6 hr a day for 21 consecutive days. Enflurane exposed females and their controls were allowed to deliver and raise their offspring. Offspring were studied for evidence of abnormal development as two day, 4, 8, 14 and 80 to 90 week old animals. Thorough gross and histopathological examinations, organ/body weight ratios, clinical chemical and hematological, and overall growth and behavioral examinations were carried out in various aged animals. Sex differences were seen in many parameters as expected, but statistically significant treatment related effects were observed only in the food maze learning behavior and in the pentobarbital sleeping time in the puberty aged male offspring. From our data we can conclude that offspring of pregnant female rats exposed to enflurane at 1500 ppm throughout gestation show minimal, if any, significant clinical or behavioral pathological effects.

Animals↗

Developmental and behavioral effects of maternal alcohol exposure in rats.

Fostered rat offspring whose mothers had been administered 7.5% alcohol solution (4.85 g/kg/day) as drinking fluid during 0-17 days of gestation were compared with equivalent groups whose dams had given ad libitum and restricted volume of tap water in the following behavioral tests: reflex test, swimming behavior test, open-field test, radial-maze learning and two-way avoidance learning. The treatment with alcohol resulted in developmental delay in ear-flaps uncurling, placing reflex, swimming behavior, walking in addition to reduction in body weight at 1 and 7 days of age. The treated group also exhibited decreased open-field activity and deficit in the avoidance learning. The results show that maternal alcohol consumption produces developmental and behavioral deficits in offspring, which are comparable to the fetal alcohol syndrome (FAS) in man.

Animals↗

Effects of prenatal naloxone exposure on postnatal behavioral development of rats.

Pregnant Sprague-Dawley rats were daily administered either 20 mg/kg or naloxone HCl in saline or saline alone IP in two divided doses on days 7-20 of gestation (i.e., 40 mg/kg/day of naloxone). The offspring were reared by their biological dams and were examined for physical, neurological and behavioral development using a battery of psychoteratogenic tests administered from postnatal day 3 to adulthood (120 days of age). The Naloxone offspring were accelerated in postweaning growth, upper incisor eruption, righting development, startle development, home scent discrimination, and in directional swimming development, but as adults, showed impaired Biel water maze learning. The current data support the concept that early exposure of rats to naloxone can produce long-term changes in development and in adult behavioral performance.

Animals↗

Performance of four different rat strains in the autoshaping, two-object discrimination, and swim maze tests of learning and memory.

The performance of four strains of rats commonly used in behavioural research was assessed in three different tests of learning and memory. The four strains included three outbred lines (Long-Evans, Sprague-Dawley, Wistar) and one inbred strain (S3). Learning and memory were tested using three different paradigms: autoshaping of a lever press, a two-object discrimination test, and performance in a two-island swim maze task. The pigmented strains showed better performance in the autoshaping procedure: the majority of the Long-Evans and the S3 rats acquired the response, and the majority of the Wistar and Sprague-Dawley failed to acquire the response in the set time. The albino strains were slightly better in the swim maze than the pigmented strains. There appeared to be a speed/accuracy trade-off in the strategy used to solve the task. This was also evident following treatment with the cholinergic-depleting agent hemicholinium-3. The performance of the Long-Evans rats was most affected by the treatment in terms of accuracy and the Wistar and Sprague-Dawleys in terms of speed. In the two-object discrimination test only the Long-Evans showed satisfactory performance and were able to discriminate a novel from a known object a short interval after initial exposure. These results show large task- and strain-dependent differences in performance in tests of learning and memory. Some of the performance variation may be due to emotional differences between the strains and may be alleviated by extra training. However, the response to pharmacological manipulation may require more careful evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗