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PubMed2005

Hallmarks of a common forebrain vertebrate plan: specialized pallial areas for spatial, temporal and emotional memory in actinopterygian fish.

In mammals and birds different pallial forebrain areas participate in separate memory systems. In particular, the hippocampal pallium is implicated in spatial memory and temporal attribute processing, whereas the amygdalar pallium is involved in emotional memory. Here we analyze the involvement of teleost fish lateral and medial pallia, proposed as homologous to the hippocampus and amygdala, respectively, in a variety of learning and memory tasks, such as spatial memory; reversal learning; delay or trace motor classical conditioning; heart rate, emotional classical conditioning; and two way active avoidance conditioning. Results show that the damage to the lateral pallium produces a profound deficit in spatial learning and memory in teleost fish. In addition, lateral pallium lesions produce a significant deficit in trace classical conditioning, whereas they have no significant effects on delay conditioning, or in heart rate conditioning. In contrast, medial pallium lesions disrupt emotional, heart rate conditioning and avoidance conditioning, but spare spatial memory and temporal stimulus processing. These data demonstrate a striking functional similarity between the medial and lateral pallia of teleost fish and the pallial amygdala and hippocampal pallium of land vertebrates, respectively. The reviewed evidence suggest that these two separate memory systems, the hippocampus-dependent spatial, relational or temporal memory system, and the amygdala based emotional memory system, could have appeared early during evolution, having conserved their functional identity through vertebrate phylogenesis.

Animals↗
PubMed1996

Spatial learning and memory in calpastatin-deficient rats.

The present experiments were concerned with the examination of the hypothesis that a deficiency in calpastatin, the endogenous inhibitor of calpain, enhances learning and memory performance. In the first experiment we used rats with an altered calpain/calpastatin balance (Milan hypertensive strain, MHS, low calpastatin) to investigate the learning and memory of a spatial task in the Morris water maze in comparison with control rats with a normal calpain/calpastatin balance (Milan normotensive strain, MNS). Since the two strains also differ in blood pressure, a third strain of rats was included to assess the role of hypertension (spontaneously hypertensive rats, SHR). Although the acquisition rate of the spatial task was better in the low-calpastatin MHS rats than in their normal-calpastatin MNS controls, their performance was similar to that of the SHR rats, thus thwarting the conclusion that differences were due to the low level of calpastatin. The availability of another mutant strain, low-calpastatin level and normotensive (MH.NE), allowed a further examination of the hypothesis. In the second experiment rats of the MH.NE strain acquired the spatial task as well as their normotensive controls, but their memory retrieval was clearly less than that of their normal-calpastatin controls. This deficiency was not due to impaired visual function or a slower swimming speed. The conclusion is that an inbalanced calpain/calpastatin ratio, although favoring calpain activity, is disadvantageous for remembering a spatial task. This disadvantage is clearly overruled when this inbalance is accompanied by hypertension.

Animals↗
PubMed2001

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↗
PubMed2002

The lesion of the rat substantia nigra pars compacta dopaminergic neurons as a model for Parkinson's disease memory disabilities.

1. In this article we review the studies of memory disabilities in a rat model of Parkinson's disease (PD). 2. Intranigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to rats causes a partial lesion in the substantia nigra, compact part (SNc) and a specific loss of dopamine and its metabolites in the striatum of rats. 3. These animals present learning and memory deficits but no sensorimotor impairments, thus modeling the early phase of PD when cognitive impairments are observed but the motor symptoms of the disease are barely present. 4. The cognitive deficits observed in these animals affect memory tasks proposed to model habit learning (the cued version of the water maze task and the two-way active avoidance task) and working memory (a working memory version of the water maze), but spare long-term spatial memory (the spatial reference version of the Morris water maze). 5. The treatment of these animals with levodopa in a dose that restores the striatal level of dopamine does not reverse these memory impairments, probably because this treatment promotes a high level of dopamine in extrastriatal brain regions, such as the prefrontal cortex and the hippocampus. 6. On the other hand, the adenosine receptor antagonist, caffeine, partly reverse the memory impairment effect of SNc lesion in these rats. This effect may be due to caffeine action on nigrostriatal neurons, since it induces dopamine release and modulates the interaction between adenosine and dopamine receptor activity. 7. These results suggest that the MPTP SNc-lesioned rats are a good model to study memory disabilities related to PD and that caffeine and other selective A(2A) adenosine receptor antagonists are promising drugs to treat this symptoms in PD patients.

Animals↗
PubMed2006

Everyday cognitive function after craniopharyngioma in childhood.

Despite clinical impressions that cognitive complaints are prominent in patients with a history of craniopharyngioma, formal neuropsychologic documentation is inconsistent. This study assessed everyday cognitive complaints and neuropsychologic test performance to evaluate the prevalence of problems and the relationship of these domains to one another in patients treated for craniopharyngioma in childhood or adolescence. Ten patients treated for craniopharyngioma completed measures of everyday cognitive function (Cognitive Failures Questionnaire, Rivermead Behavioural Memory Test) and a battery of standard neuropsychologic tests. The prevalence of problems was ascertained for each measure. Most patients demonstrated significant deficits in everyday memory (Cognitive Failures Questionnaire, 9/10 patients; Rivermead Behavioural Memory Test, 7/10 patients). Scores were within normal limits, however, for intelligence quotient, achievement, attention, verbal memory, and spatial working memory. Processing speed was slow (5/10 patients). Spatial working memory predicted Cognitive Failures Questionnaire (P < 0.07), as did somatic symptoms from the Beck Depression Inventory (P < 0.01), but these associations appeared independent. Adolescents and young adults with treated craniopharyngioma experience deficits in everyday cognitive functions, many involving memory, that are not easily detected by standard neuropsychologic testing. The extent of self-rated cognitive problems is related to spatial working memory and somatic concerns.

Activities of Daily Living↗
PubMed2003

Memory and hippocampal specialization in food-storing birds: challenges for research on comparative cognition.

The three-way association among food-storing behavior, spatial memory, and hippocampal enlargement in some species of birds is widely cited as an example of a new 'cognitive ecology' or 'neuroecology.' Whether this relationship is as strong as it first appears and whether it might be evidence for an adaptive specialization of memory and hippocampus in food-storers have recently been the subject of some controversy [Bolhuis and Macphail, 2001; Macphail and Bolhuis, 2001]. These critiques are based on misconceptions about the nature of adaptive specializations in cognition, misconceptions about the uniformity of results to be expected from applying the comparative method to data from a wide range of species, and a narrow view of what kinds of cognitive adaptations are theoretically interesting. New analyses of why food-storers (black-capped chickadees, Poecile Atricapilla) respond preferentially to spatial over color cues when both are relevant in a memory task show that this reflects a relative superiority of spatial memory as compared to memory for color rather than exceptional spatial attention or spatial discrimination ability. New studies of chickadees from more or less harsh winter climates also support the adaptive specialization hypothesis and suggest that within-species comparisons may be especially valuable for unraveling details of the relationships among ecology, memory, and brain in food-storing species.

Animals↗
PubMed1986

Cholinergic septal grafts into the hippocampal formation improve spatial learning and memory in aged rats by an atropine-sensitive mechanism.

Behaviorally impaired old rats were selected from a population of 75 21- to 23-month-old rats on the basis of the place-investigated abilities in the Morris' water-maze task. After the pretransplant test, half of the old impaired rats received bilateral intrahippocampal cell suspension grafts prepared from the fetal septal-diagonal band region, which is rich in developing cholinergic neurons; the other half were left as sham-operated controls. Twelve weeks after grafting, the rats were retested in the water-maze using alternating cue-navigation and place-navigation trials (i.e., with visible or nonvisible escape platform). While the old impaired controls had deteriorated further between the 2 tests and showed poor retention of the pretransplant performance level, the grafted rats were significantly improved in comparison with both their pretransplant performance and the performance of the old impaired controls in the posttransplant test. The graft-induced effect was due both to an improved retention of the performance level acquired in the test performed prior to transplantation surgery, and to an improved acquisition of spatial memory of the escape platform site during the posttransplant test week (measured as an improved focusing of search over the platform site after platform removal). The acetylcholine esterase inhibitor physostigmine had no or only marginal effects on the performance of any of the young or aged rat groups. By contrast, the recovered navigational abilities and spatial memory in the grafted animals were completely abolished after administration of the muscarinic receptor antagonist atropine. A similar atropine-sensitivity was seen in behaviorally nonimpaired aged rats but not in the well-trained young control rats. The results show that cholinergic septal grafts, implanted into the hippocampal formation, improved spatial learning in the impaired aged rats primarily, or perhaps exclusively, by a recovery of the rats' ability to use spatial cues for place-navigation in the water-maze, while other aspects of the performance deficits in the water-maze task in the aged rats were left unaffected by the septal grafts. On the basis of parallel morphological studies, it is proposed that the effects of the septal grafts on the spatial learning impairments in the aged rats are critically dependent on the direct action of cholinergic neurons in the grafts via synapses formed onto neuronal elements in the host by their ingrowing axons.

Aging↗
PubMed2000

Lidocaine reversible inactivation of the median raphe nucleus has no effect on reference memory but enhances working memory versions of the Morris water maze task.

Numerous studies in the past have dealt with the role of serotonergic system lesions in tasks aimed at measurement of cognitive behavior, but the literature concerning the role of serotonin in cognition remains controversial. Rats with electrolytic lesions of the median raphe nucleus (MRN) were found to display a profound impairment in both the acquisition and retention of spatial memory task. In this study, the lidocaine inactivation was employed to evaluate the involvement of the rat's median raphe nucleus in reference and working memory versions of the Morris water maze (MWM) task. Lidocaine (0.5 microl, 2%) was injected through a single cannula aimed at the MRN; control groups were treated in the same way with a 0.5 microl injection of saline. In Experiment 1, rats were trained in a reference memory version of the MWM with two blocks of four trials per day for three consecutive days, with intra-cerebral injection made 5 min before training. No significant difference was found. In Experiment 2, intra-cerebral injection was applied immediately after two blocks of four trials, and in Experiment 3, the drug was injected 5 min before retention test in rats that had received eight trials per day on three consecutive days. Again, no significant difference between control and treatment groups was found. These results indicate that MRN has no role in acquisition, consolidation and retrieval of spatial reference memory. In subsequent experiments, rats were trained in a working memory version of the MWM task to find a new target position in trial 1, and retrieval was tested 75 min later. MRN inactivation 5 min before (Experiment 4) and immediately after the acquisition trial (Experiment 5) enhanced spatial working memory. It is concluded that normal activity of the MRN has no role in formation and retrieval of reference memory, but it has an inhibitory role in working memory. Our results are confirmed with other studies suggesting that the serotonergic system has a different role in long-term and short-term memory. Interaction with other neurotransmitter systems like acetylcholine may be involved in this case.

Anesthetics, Local↗
PubMed1995

Spatial learning and memory as a function of age in the dog.

Spatial learning and memory were studied in dogs of varying ages and sources. Compared to young dogs, a significantly higher proportion of aged dogs could not acquire a spatial delayed nonmatching-to-sample task. A regression analysis revealed a significant age effect during acquisition. Spatial memory was studied by comparing performance at delay interval of 20, 70, and 110 s. At short delays aged and young dogs were similar; at longer delays, errors increased to a greater extent in old than in young dogs; however this was not statistically significant. It was possible to identify 2 groups of aged animals, age-impaired and age-unimpaired. Several of the dogs were also tested on an object recognition memory task, which was more difficult to learn than the spatial task. The possibility that these findings are confounded by breed differences is considered. Overall, the present results provide further evidence of the value of a canine model of aging.

Aging↗
PubMed2004

Retrosplenial cortex lesions of area Rgb (but not of area Rga) impair spatial learning and memory in the rat.

The retrosplenial cortex, which is situated in a critical position in the flow of information between the hippocampal formation and the neocortex, contributes to spatial memory, but no studies have examined the distinct contribution of each area of the retrosplenial cortex to this behavior. This study tests the hypothesis that the two areas of the retrosplenial granular cortex play distinct roles in spatial learning and memory. Adult, male Sprague-Dawley rats with small, bilateral lesions (ibotenic acid) of the retrosplenial granular cortex were tested for 2 weeks in a repeated acquisition water maze task. Compared to controls, rats with complete lesions of the retrosplenial granular b cortex (Rgb) were slightly, but significantly impaired, whereas rats with lesions of the retrosplenial granular a cortex (Rga) displayed no impairment. Further, the Rgb-lesioned (but not the Rga-lesioned) group was impaired in the probe trials at the end of the first week of training. All animals were tested in the same paradigm for a second week to determine if the learning and memory impairment in the Rgb-lesioned rats simply reflected "delayed learning." All animals improved their maze performance during the second week of testing, but the Rgb-lesioned group still had no preference for the correct quadrant in the probe trial. Together, these data indicate that Rgb plays a small, independent role in spatial learning and memory. Further, although selective lesions of Rga or Rgb do not cause a large deficit in learning, concomitant destruction of both areas causes a much greater impairment in learning than would be predicted from their independent contributions. The data highlight the unique and complex contribution of each area of the retrosplenial cortex to behavior.

Animals↗
PubMed1995

View-responsive neurons in the primate hippocampal complex.

Recordings were made from single neurons in the hippocampus and parahippocampal gyrus while macaques were moved on a platform mounted on a free-moving robot or on wheels in a cue-controlled 2 m x 2 m x 2 m environment, in order to investigate the representation of space and of spatial memory in the primate hippocampus. The test conditions allowed factors that might account for spatial firing of the cells, including the spatial location where the monkey looked, the place were the monkey was, and the head direction of the monkey, to be identified. The responses of some ("view") neurons depended on where the monkey was looking in the environment, but not on the place of the monkey in the environment. The responses of one other neuron depended on a combination of where the monkey was facing and his place in the test chamber. The response of view-dependent neurons was affected by occlusion of the visual field. It was possible to show for one neuron that its "view" response rotated with rotation of the test chamber. Some neurons responded to a combination of whole-body motion and view or place, and one neuron responded in relation to whole-body movement to a particular place. One neuron responded depending on the place where the monkey was in the environment and relatively independently of view. The representations of space provided by hippocampal view-responsive neurons may be useful in forming memories of spatial environments (for example, of where an object has been seen and of where the monkey is as defined by seen views) and, together with whole-body motion cells, in remembering trajectories through environments, which is of use, for example, in short range spatial navigation.

Animals↗
PubMed1999

Neural topography and chronology of memory consolidation: a review of functional inactivation findings.

Findings on the role of subcortical and cortical structures in mnemonic processes, obtained by means of the reversible functional inactivation technique, are reviewed. The main advantage of this method (subcortical or cortical administration of local anesthetics or tetrodotoxin) is that it provides information not only on "where" but also "when" and for "how long" these processes take place, thus adding to the topographical dimension the chronological one. The review covers several types of memory (e.g., passive avoidance and spatial memory) studies examining the neural substrates of memory consolidation on the basis of the functional inactivation of the nucleus of the solitary tract, parabrachial nuclei, substantia nigra, hippocampus (dorsal and ventral), nucleus basalis magnocellularis, amygdala, medial septal area, striatum, olfactory bulb, and neocortex. The data are discussed in relation to earlier research and with respect to the anatomical and functional connectivity of the examined centers.

Anesthetics, Local↗
PubMed2000

Chronic exposure to low-level lead impairs learning ability during aging and energy metabolism in aged rat brain.

The neurotoxic effect of chronic exposure to low-level lead (Pb) with advancing age is becoming an important social issue of public health. To examine the effects of low-level Pb treatment on behavior, cognition and brain energy metabolism in aging, we administered 200 ppm Pb acetate to adult (10-month-old) male Wistar rats for 12.5 months. After 12.5 months' exposure, the mean Pb levels in blood and brain had increased to 17.5 µg/dl and 0.07 µg/g, respectively, and the rats showed impaired learning and memory functions in a holeboard spatial memory test. No significant difference was found between experimental and control groups in locomotor activity and passive avoidance tests. By HPLC analysis of energy-rich phosphate concentrations, mild abnormalities were found in parietotemporal cortex and hippocampus, but only the 4.4% decrease of ATP in the parietotemporal cortex was statistically significant. These results suggest that chronic exposure to Pb during aging stage may selectively impair learning and memory functions and may cause slight cerebral energy impairment.

Journal Article↗
PubMed2000

Formation of temporal memory requires NMDA receptors within CA1 pyramidal neurons.

In humans the hippocampus is required for episodic memory, which extends into the spatial and temporal domains. Work on the rodent hippocampus has shown that NMDA receptor (NMDAR) -mediated plasticity is essential for spatial memory. Here, we have examined whether hippocampal NMDARs are also needed for temporal memory. We applied trace fear conditioning to knockout mice lacking NMDARs only in hippocampal CA1 pyramidal cells. This paradigm requires temporal processing because the conditional and unconditional stimuli are separated by 30 s (trace). We found that knockout mice failed to memorize this association but were indistinguishable from normal animals when the trace was removed. Thus, NMDARs in CA1 are crucial for the formation of memories that associate events across time.

Animals↗
PubMed1999

Episodic memory and learning in patients with chronic schizophrenia.

This study explored the pattern of memory functioning in 58 patients with chronic schizophrenia and compared their performance with 53 normal controls. Multiple domains of memory were assessed, including verbal and non-verbal memory span, verbal and non-verbal paired associate learning, verbal and visual long-term memory, spatial and non-spatial conditional associative learning, recognition memory and memory for temporal order. Consistent with previous studies, substantial deficits in long-term memory were observed, with relative preservation of memory span. Memory for temporal order and recognition memory was intact, although significant deficits were observed on the conditional associative learning tasks. There was no evidence of lateralized memory impairment. In these respects, the pattern of memory impairment in schizophrenia is more similar in nature to that found in patients with memory dysfunction following mesiotemporal lobe lesions, rather than that associated with focal frontal lobe damage.

Adult↗
PubMed1997

Memory consolidation, retrograde amnesia and the hippocampal complex.

Results from recent studies of retrograde amnesia following damage to the hippocampal complex of human and non-human subjects have shown that retrograde amnesia is extensive and can encompass much of a subject's lifetime; the degree of loss may depend upon the type of memory assessed. These and other findings suggest that the hippocampal formation and related structures are involved in certain forms of memory (e.g. autobiographical episodic and spatial memory) for as long as they exist and contribute to the transformation and stabilization of other forms of memory stored elsewhere in the brain.

Amnesia↗
PubMed1999

The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia.

Cognitive function is markedly impaired in most patients with schizophrenia. Antecedents of this impairment are evident in childhood. The cognitive disability is nearly fully developed at the first episode of psychosis in most patients. The contribution of cognitive impairment to outcome in schizophrenia, especially work function, has been established. Preliminary results indicate that cognitive function, along with disorganization symptoms, discriminate schizophrenia patients who are able to work full-time from those who are not. Typical neuroleptic drugs lack the ability to improve the various domains of cognitive function impaired in schizophrenia. Atypical antipsychotic drugs pharmacologically related to clozapine-quetiapine, olanzapine, risperidone, sertindole, and ziprasidone--share the ability to produce fewer extrapyramidal symptoms than typical neuroleptic drugs and more potent antagonism of serotonin2a relative to dopamine2 receptors. However, they have a number of different clinical effects. We have identified all the studies of clozapine, olanzapine, and risperidone that provide data on their effects on cognition in schizophrenia. Data for each drug are reviewed separately in order to identify differences among them in their effects on cognition. Twelve studies that report cognitive effects of clozapine are reviewed. These studies provide (1) strong evidence that clozapine improves attention and verbal fluency and (2) moderate evidence that clozapine improves some types of executive function. However, results of the effects of clozapine on working memory and secondary verbal and spatial memory were inconclusive. Risperidone has relatively consistent positive effects on working memory, executive functioning, and attention, whereas improvement in verbal learning and memory was inconsistent. Preliminary evidence presented here suggests that olanzapine improves verbal learning and memory, verbal fluency, and executive function, but not attention, working memory, or visual learning and memory. Thus, atypical antipsychotic drugs as a group appear to be superior to typical neuroleptics with regard to cognitive function. However, available data suggest that these drugs produce significant differences in specific cognitive functions. These differences may be valuable adjunctive guides for their use in clinical practice if cognitive improvements reach clinical significance. The effects of the atypical antipsychotic drugs on cholinergic and 5-HT2a-mediated neurotransmission as the possible basis for their ability to improve cognition are discussed. It is suggested that the development of drugs for schizophrenia should focus on improving the key cognitive deficits in schizophrenia: executive function, verbal fluency, working memory, verbal and visual learning and memory, and attention.

Antipsychotic Agents↗
PubMed2006

Predicting cognitive styles from spatial abilities.

Previous studies on spatial memory reveal that people represent spatial information in 3 different forms: landmark, route, and survey. The aim of this work was to assess spatial abilities in order to predict a person's cognitive style. In order to do this we used 9 different spatial tasks, which were linked with these 3 forms of spatial representations. We found that the 9 spatial tasks are able to distinguish different levels of spatial ability.

Adult↗

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