Place Learning Ability Research Articles

Rapid learning of a spatial memory task in a lacertid lizard (Podarcis liolepis)

Mammals and birds are capable of navigating to a goal using learned map-like representations of space (i.e. place learning), but research assessing this navigational strategy in reptiles has produced inconclusive results, in part due to the use of procedures that do not take account of the peculiarities of reptilian behavior and physiology. Here I present a procedure suitable for testing spatial cognition that exploits a naturally evolved, ethologically relevant ability common to many lizards (i.e. refuge seeking behavior). The procedure requires lizards to learn the location of an open refuge inside a rectangular arena containing artificial refuges in every corner, using distal extramaze visual cues and with no local cues marking the location of the open refuge. The procedure probes the lizards’ place learning ability and effectively rules out the use of egocentric and response-based strategies. The described procedure was successfully used to demonstrate place learning in a lacertid lizard (Podarcis liolepis). Over the course of two weeks of training both the latency to entering the open refuge and the number of corners visited in each trial decreased gradually, indicating that learning had taken place in over 60% of the lizards tested. These results confirm that, under certain circumstances, lizards are capable of navigating to a goal using a place learning strategy.

Neonatal Monosodium Glutamate Administration Disrupts Place Learning and Alters Hippocampal–Prefrontal Learning-Related Theta Activity in the Adult Rat

Neonatal treatment with monosodium glutamate causes profound deficits in place learning and memory in adult rats evaluated in the Morris maze. Theta activity has been related to hippocampal learning, and increased high-frequency theta activity occurs through efficient place learning training in the Morris maze. We wondered whether the place learning deficits observed in adult rats that had been neonatally treated with monosodium glutamate (MSG), were related to altered theta patterns in the hippocampus and prelimbic cortex, which were recorded during place learning training in the Morris maze. The MSG-treated group had a profound deficit in place learning ability, with a marginal reduction in escape latencies during the final days of training. Learning-related changes were observed in the relative power distribution in control and MSG-treated groups in the hippocampal EEG, but not in the prelimbic cortex. Increased prefrontal and reduced hippocampal absolute power that appeared principally during the final days of training, and reduced coherence between regions throughout the training (4–12 Hz), were observed in the MSG-treated rats, thereby suggesting a misfunction of the circuits rather than a hyperexcitable general state. In conclusion, neonatal administration of MSG, which caused a profound deficit in place learning at the adult age, also altered the theta pattern both in the hippocampus and prelimbic cortex.

N-Acetyl-D-Mannosamine Treatment Alleviates Age-Related Decline in Place-Learning Ability in Dogs

ABSTRACTThis study aimed to investigate the therapeutic effects of N-acetyl-D-mannosamine (ManNAc) on age-related cognitive dysfunction in dogs. ManNAc was administered to 5 dogs with low cognitive levels for 2 months, and the cognitive ability and active-resting cycle were periodically assessed for improvement. ManNAc treatment significantly reduced the number of error trials in the place-learning test, especially in the first month of administration. Three ManNAc-treated dogs also showed improvement in the active-resting cycle. In conclusion, ManNAc treatment appears to alleviate age-related cognitive dysfunction.

Serotonin depletion of supramammillary/posterior hypothalamus nuclei produces place learning deficiencies and alters the concomitant hippocampal theta activity in rats

Hippocampal theta activity is important for the acquisition of spatial information and is strongly influenced and regulated by extra-hippocampal inputs from the synchronising ascending system (SAS), which includes the supramammillary nucleus (SUMn) and the posterior hypothalamic nucleus (PHn). Together these nuclei play an important role in controlling the frequency encoding of theta activity and are innervated by serotonin synapses, which also regulate theta activity and learning abilities. The participation of the SUMn in place learning and modulation of hippocampal theta activity were recently shown; thus, we questioned whether serotonin acting on SUMn/PHn could modulate place learning ability and concurrent hippocampal theta activity. The serotonergic terminals of the SUMn/PHn in rats were lesioned through 5,7-dihydroxytryptamine (5,7-DHT) infusion, and hippocampal theta activity during the Morris water maze test was recorded. Rats in the vehicle group learned the task efficiently and showed learning-related theta changes in the CA1 and dentate gyrus regions throughout the training. The 5-HT-depleted rats were deficient in the Morris water maze task and showed theta activity in the CA1 and dentate gyrus that were unrelated to the processing of learning. We conclude that serotonin can regulate the hippocampal theta activity acting on the SUMn/PHn relay of the SAS and that the influence of 5-HT in these nuclei is required for the learning-related changes in hippocampal theta activity that underlie the successful resolution of the Morris water maze task.

Differential learning-related changes in theta activity during place learning in young and old rats

The participation key role of the hippocampus in place learning ability as well as the decline of cognitive functions associated with aging, have been established in experimental and clinical studies. On the other hand, hippocampal theta activity has been proposed as a part of the cerebral phenomena underlying hippocampal-dependent learning processes. In the present study, the relative power of low, high, and maximal frequency components of hippocampal CA1 theta activity during a 6-day training period (four daily trials; basal, searching, and platform stages) and the probe trial of a place learning paradigm (Morris water maze) were analyzed in young and aged rats. An increase in high frequency, and a decrease in low frequency relative power of theta activity during the searching stage, which were correlated with shorter swimming path lengths and predominant hippocampal-dependent allocentric strategies, were observed in young rats as became trained in place learning and memory tasks, in the Morris water maze; while, under these conditions, no changes in theta activity and predominant non hippocampal-dependent egocentric strategies occurred in the old rats. Besides, an overall (theta activity recorded during the three behavioral stages) increase of low frequency and an overall decrease of high frequency theta bands in the old group as compared to the young group were observed. These electrophysiological data suggest that old rats process information relevant for cognitive functions in a different manner, possibly leading to the use of different learning strategies, than young rats.

Testing time–place learning in the cichlid fish Nile tilapia

Time–place learning based on food association was investigated in the fish Nile tilapia. During a 30-day period, food was placed at one side of the aquarium (containing three compartments) in the morning and at the opposite side in the afternoon. Learning was inferred by the number of correct side choices of all fish in each day of test (15th, 30th). During the test day, fish were not fed. The Nile tilapia did not learn to switch sides at the correct day period in order to get food, suggesting thus that this species does not have time–place learning ability.

Neonatal exposure to monosodium glutamate disrupts place learning ability in adult rats

The activation of glutamatergic NMDA receptors of the hippocampus is closely associated with expression of place learning. Neonatal exposure to monosodium glutamate leads to abnormal expression of NMDA receptor subunits in the hippocampus, but its effect on place learning is unknown. Place learning acquisition and retrieval were assessed in mature adult rats after subcutaneous injection of monosodium glutamate (4 mg/g body weight) in eight neonatal rat pups at postnatal days one, three, five, and seven. Eight untreated rats were used as controls. At four months of age, the rats were challenged over a period of nine days with a place learning task. The task used an acquisition–retrieval paradigm in a Morris maze. Place learning acquisition was impaired in the experimental rats, which were unable to reduce their escape latencies during the nine training days. Controls improved between the fifth and ninth days of training. Test trials showed that retrieval of spatial information was also impaired in the experimental animals. These results show that both place learning acquisition and retrieval abilities in mature rats are impaired by neonatal treatment with monosodium glutamate. These findings may be related to the abnormal expression of NMDA receptor subunits in the hippocampus.

Spatial navigation related to the ratio of second to fourth digit length in women

Prenatal gonadal hormones have been implicated as important factors in the development of different spatial abilities, including spatial navigation. The aim of the study reported here was to examine the relationship between navigational abilities and the second-to-fourth digit ratio (2D:4D ratio) in healthy women. There is evidence that the ratio of the length of second and fourth digits is negatively related to prenatal testosterone and positively positively related to prenatal estrogen. In this study, the 2D:4D ratio was measured in a sample of 46 female university students. The subjects' place learning ability was tested in a real arena maze (RAM). Our results tend to support an association between prenatal gonadal hormone concentration and some aspects of spatial navigation. The subjects with lower 2D:4D ratio had significantly longer hidden platform-finding latency, better spatial recall, and selected significantly more navigation cues in a posttest of the arena maze learning.

Chapter 11 Modification of dendritic development

Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the hippocampal Ammon's horn and, particularly, on the CA1 field pyramidal neurons, as well as on afferences to the hippocampus which needs to be further investigated.

Normal Spatial Learning and Improved Spatial Working Memory in Mice (<em>Mus musculus</em>) Lacking Dopamine D4 Receptors

Dopamine terminals in the hippocampus and prefrontal cortex modulate cognitive processes such as spatial learning and working memory. Because dopamine D4 receptors are expressed in these brain areas we have analyzed mutant mice lacking this receptor subtype (D rd4 -/-). Wild-type and D rd4 -/- mice were challenged in two spatial learning paradigms: the Morris water maze and an alternation T-maze. D rd4 -/- mice showed normal place learning ability to find a hidden platform based on spatial extra-maze cues. In addition, Drd4 -/- mice were able to find a new platform location with the same learning plasticity as wild type-mice. Spatial working memory assessed on a T maze showed that Drd4 -/- mice were more efficient than wild-type mice in acquiring the maximum plateau of correct alternation scores. These results provide further evidence that the functional consequence of lacking D4 receptors is more evident in behaviors dependent on the integrity of the prefrontal cortex.

A characterization of performance by men and women in a virtual Morris water task:: A large and reliable sex difference

In many mammalian species, it is known that males and females differ in place learning ability. The performance by men and women is commonly reported to also differ, despite a large amount of variability and ambiguity in measuring spatial abilities. In the non-human literature, the gold standard for measuring place learning ability in mammals is the Morris water task. This task requires subjects to use the spatial arrangement of cues outside of a circular pool to swim to a hidden goal platform located in a fixed location. We used a computerized version of the Morris water task to assess whether this task will generalize into the human domain and to examine whether sex differences exist in this domain of topographical learning and memory. Across three separate experiments, varying in attempts to maximize spatial performance, we consistently found males navigate to the hidden platform better than females across a variety of measures. The effect sizes of these differences are some of the largest ever reported and are robust and replicable across experiments. These results are the first to demonstrate the effectiveness and utility of the virtual Morris water task for humans and show a robust sex difference in virtual place learning.

Place Learning in Hippocampal Rats and the Path Integration Hypothesis

WHISHAW, I. Q. Place learning in hippocampal rats and the path integration hypothesis. NEUROSCI. BIOBEHAV. REV. 22(2), 209–210, 1998.—Although two decades of research suggests that the hippocampus plays a special role in place learning, the present paper describes a series of studies using swimming pool spatial tasks that show that hippocampal rats have considerable place learning ability, which includes the abilities of finding, remembering, and searching for places. The same studies also show that when environmental cues are uninformative, as is the case early in original learning and again in reversal learning, hippocampal rats are impaired. Since control rats quickly resolve spatial ambiguity in these situations, it is argued that they must have a system with which they can calibrate spatial cues. The discussion considers the possibility that they use dead reckoning with path integration, a spatial strategy that provides guidance based on cues generated by a point of reference and subsequent self-movement and not the cues in the environment through which they are moving. With path integration an animal can monitor its location and at the same time attach spatial meaning to cues that it encounters. An ability to recalibrate external cues may provide the tuning that allows control rats to quickly acquire place responses while hippocampal rats are constrained by the processes of associative learning.

Behavioral symptoms in adult rats after postnatal l-nitro-arginine

We addressed experimentally the suggestion by Gally et al. [Gaily J. A., Read Montague P., Reeke G. N. Jr and Edelman G. M. (1990) Proc. Natl Acad. Sci. U.S.A.87, 3547–3551] that nitric oxide may play a role in the use-dependent modification of synaptic efficacy in the developing nervous system. In a preliminary control experiment, we treated rat pups from postnatal day 8 to postnatal day 22 with a nitric oxide synthase blocker (l-nitro-arginine) and compared their growth curves and brain weights to those of saline injected control pubs. No significant differences were found after the 14 days of nitric oxide synthase inhibition. In the subsequent experiment, we inhibited nitric oxide synthesis in rat pups from postnatal day 8 to day 29 and assessed their place learning ability and open field behavior as adults. We found an increased speed of habituation of locomotion in an open field in 5-month-old rats that had been treated postnatally with a nitric oxide synthase blocker. There was no difference between treated and nontreated rats with respect to place learning in a water maze. We conclude that perturbation of nitric oxide production during early postnatal development does not preclude normal learning and memory function in the adult.

Spatial learning in male and female Long-Evans rats.

Male and female Long-Evans rats were tested in the Morris water maze at 6 months of age. A place training procedure, in which rats learned the position of a camouflaged platform, was followed by cue training, in which rats escaped to a visible platform. No sex difference was found in place learning ability. Search accuracy on probe trials, when the platform was unavailable, was also equivalent for the male and female groups. These results contrast with previous studies of rodents at younger ages, which have reported a male advantage in spatial learning. It is suggested that the age at which rats are assessed may be an important factor, possibly reflecting a different course in the relatively protracted maturation of the hippocampus in male and female rats. The results of this investigation are also discussed with reference to studies of sex differences for spatial abilities in humans.

Alterations in [3H]-kainate receptor binding in the hippocampal formation of aged Long-Evans rats.

The present study used in vitro autoradiography to examine the density of [3H]-kainate (KA) binding in subregions of the hippocampal formation and certain cortical areas in young (7-8 months) and aged (27-29 months) Long-Evans rats. In addition, the topography of KA binding in the dentate molecular layer was examined for evidence of reactive reorganization in the aged brain. This investigation of age-related changes in [3H]-KA binding included correlations with the animals' spatial learning performance in a Morris water maze. The results showed an age-related decrease in the density of [3H]-KA binding in several regions of the hippocampal formation (CA3, CA1, hilus) and within related cortical areas (subicular complex, entorhinal cortex, perirhinal cortex). In addition, an expanded zone of KA binding in the molecular layer of the dentate gyrus was observed in the aged group. This expansion of KA binding may reflect sprouting due to a loss of perforant path input to the dentate. The results of additional correlational analyses, however, indicated that these changes in the density and topography of [3H]-KA binding were not strongly correlated with a decline in place learning ability.

Increased responsiveness of hippocampal pyramidal neurons to nicotine in aged, learning-impaired rats

The effect of aging upon the responsiveness of hippocampal CA1 pyramidal neurons to nicotine was investigated using electrophysiological techniques in male Fischer 344 rats. Prior to electrophysiological recording, animals were behaviorally tested using the Morris water maze. All 3–6 and 18–21 month rats displayed rapid place learning in this task, while none of the 27–30 month animals learned within the 5-day test period. By contrast, rats of all age groups were able to learn a cue version of the water maze task. Following behavioral testing, the animals were anesthetized with sodium pentobarbital for acute recording. Nicotine was locally applied to electrophysiologically identified CA1 pyramidal neurons using pressure microejection from two-barreled glass microelectrodes. For each neuron, a dose of nicotine was found which elicited a 300–400% increase in basal firing rate. These data were used to construct cumulative dose response curves for populations of neurons tested in 3–6-, 18–21-, and 27–30-month-old animals. An age-related increase in the responsiveness of CA1 pyramidal neurons to locally applied nicotine was observed. The results of this study suggest that an increase in hippocampal CA1 pyramidal cell responsiveness to nicotine could be related to the impaired place learning ability seen with aging.