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Investigation of mechanisms mediating 8-OH-DPAT-induced impairment of spatial memory: involvement of 5-HT1A receptors in the dorsal hippocampus in rats.

The purpose of this study was to identify mechanisms that mediate the impairment of spatial memory induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A/5-HT7 receptor agonist, in the eight-arm radial maze in rats. WAY-100635 and NAN-190, 5-HT1A receptor antagonists, reversed the impairment of spatial memory induced by systemic injection of 8-OH-DPAT (1 mg/kg, i.p.). On the other hand, the alpha1-adrenoceptor antagonist prazosin and a selective 5-HT7 receptor antagonist SB269970 had no effect on 8-OH-DPAT-induced impairment of spatial memory. Bilateral microinjection of 8-OH-DPAT (4 microg/side) impaired spatial memory when injected into the dorsal hippocampus (DH). Contrastingly, spatial memory was unaffected by microinjections of 8-OH-DPAT into the other six areas examined: ventral hippocampus (VH), central amygdaloid nucleus (ACE), lateral hypothalamus (LH), nucleus accumbens (NAc), and dorsal (DR) and median (MR) raphe nucleus. Furthermore, NAN-190 significantly reversed the impairment of spatial memory induced by intra-DH injection of 8-OH-DPAT. These findings suggest that 5-HT1A receptors in the DH play an important role in the mechanisms underlying the 8-OH-DPAT-induced impairment of spatial memory in rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Subjective hierarchies in spatial memory.

Two experiments investigated the structure of spatial memories. Subjects learned locations of objects in spatial layouts (Experiment 1) or locations of object names on maps (Experiment 2). Physical and perceptual boundaries were absent in these spatial arrays. Subjects then participated in three tasks: item recognition, in which the variable of interest was spatial priming; free and cued recall; and Euclidean distance estimation. Ordered-tree analysis of individual subjects' recall protocols produced hierarchical trees consistent with regularities in output order. Spatial priming and distance estimations depended on whether pairs of objects appeared in the same subtree or in different subtrees. These findings indicate that spatial memories have a hierarchical component, even when physical and perceptual boundaries are nonexistent. Priming also increased with depth of clustering in ordered trees. This result supports spreading-activation theories of retrieval but provides evidence against several "non-spreading-activation" theories.

Adult↗

A comparison of egocentric and allocentric spatial memory in medial temporal lobe and Korsakoff amnesics.

Two patients with medial temporal lobe damage, seven Korsakoff amnesics and fourteen healthy control subjects were tested on three conditions of a spatial memory test ('short delay', 'allocentric' and 'egocentric'). The task required subjects to recall the position of a single spot of light presented on a board after various delays. The 'short delay' condition tested memory over very short, unfilled intervals. The other two conditions used longer, filled delays. The allocentric condition required subjects to move to a different place around the board before recalling the position of the light. In the egocentric condition stimuli were presented in darkness, which eliminated allocentric cues. The Korsakoff amnesics were impaired at all delays of the short delay tasks, suggesting poor encoding. On the allocentric and egocentric tasks the Korsakoff amnesics showed a comparable impairment in the two conditions, which worsened with delay. This accelerated forgetting suggested that the Korsakoff amnesics also had impaired memory for allocentric and egocentric information. The patients with medial temporal lobe damage were unimpaired in the 'short delay' condition suggesting intact encoding and short-term memory of spatial information. However, they were impaired in the allocentric condition and showed accelerated loss of allocentric spatial information. In the egocentric condition, while the performance of one patient was impaired, the performance of the other was as good as controls. This result suggests that, in contrast to allocentric spatial memory, which is sensitive to medial temporal lobe damage, an intact medial temporal lobe need not be necessary for successful performance on an egocentric spatial memory task.

Aged↗

Visual and proprioceptive representations in spatial memory.

It has been shown that spatial information can be acquired from both visual and nonvisual modalities. The present study explored how spatial information from vision and proprioception was represented in memory, investigating orientation dependence of spatial memories acquired through visual and proprioceptive spatial learning. Experiment 1 examined whether visual learning alone and proprioceptive learning alone yielded orientation-dependent spatial memory. Results showed that spatial memories from both types of learning were orientation dependent. Experiment 2 explored how different orientations of the same environment were represented when they were learned visually and proprioceptively. Results showed that both visually and proprioceptively learned orientations were represented in spatial memory, suggesting that participants established two different reference systems based on each type of learning experience and interpreted the environment in terms of these two reference systems. The results provide some initial clues to how different modalities make unique contributions to spatial representations.

Adolescent↗

The effect of chronic fluoxetine treatment on brain corticosteroid receptor mRNA expression and spatial memory in young and aged rats.

As rats age, a subgroup will show spatial memory impairments, along with decreased corticosteroid receptors (MR and/or GR) in the hippocampus and a hyperactive hypothalamic-pituitary-adrenal axis. In previous work, we have shown that amitriptyline treatment increases hippocampal MR mRNA and improves spatial memory in young rats but had no effect in aged rats. Here, we examine the effect of 1-month treatment with the selective 5-HT re-uptake inhibitor, fluoxetine (10 mg/kg, p.o.) on hippocampal corticosteroid receptor mRNA and spatial memory in young 4-month-old and aged 24-month-old rats. Aged rats were impaired in spatial memory compared to young controls. MR mRNA expression was reduced with ageing in all hippocampal subfields except CA4 (35% decrease in dentate gyrus (DG) and CA2, P<0.05) and GR mRNA was decreased selectively in CA1 (17% decrease, P<0.05). Fluoxetine treatment increased GR mRNA in the hippocampus of young rats (24 and 46% increase in DG and CA3, respectively, P<0.01) but had no effect on hippocampal MR mRNA expression. In contrast, in aged rats, fluoxetine treatment increased hippocampal MR mRNA selectively in CA2 (43% increase, P<0.05), but had no effect on hippocampal GR mRNA. Fluoxetine treatment did not alter watermaze performance in either young or aged rats. It appears that increased hippocampal MR (at least in the CA2 region) which may underlie the enhancement in memory processing in young rats, is insufficient to improve memory in already cognitively impaired aged rats.

Aging↗

Hippocampal tissue transplants reverse lesion-induced spatial memory deficits in zebra finches (Taeniopygia guttata).

The avian hippocampal formation (Hf) plays an important role in spatial memory for food storing. Here we examined the effects of excitotoxic lesions of the Hf and subsequent neural transplantation on a one-trial associative memory task in zebra finches. The results showed (1) that small ibotenic acid lesions of the dorsal Hf of zebra finches produced significant spatial memory impairments compared with controls, sham-lesioned birds, and prelesion performance; and (2) that Hf-lesioned birds given transplants of embryonic hippocampal (H) tissue, but not those given transplants of embryonic anterior telencephalon (AT) tissue, showed a significant reversal of the performance deficits on the spatial memory task. Lesioned-only birds and lesioned birds given H or AT transplants that did not survive did not show behavioral improvement. Sham-lesioned and untreated control birds maintained good performance throughout the experiment. The H and AT transplants were found to be growing partially within the Hf and partially within the underlying ventricle. The transplants appeared healthy and contained neurons with beaded and unbeaded fibers (shown by immunohistochemistry with antibodies to parvalbumin, substance P, and a 200 kDa neurofilament protein). Blood vessels and erythrocytes were also present within the transplants. The results show that neural transplants can survive within the bird brain and that small lesions of the Hf produce significant spatial memory deficits that can only be reversed by surviving homologous H transplants, and not by heterologous telencephalon transplants.

Animals↗

Retrograde amnesia in rats with lesions to the hippocampus on a test of spatial memory.

The present study examined remote spatial memory in a test that spans several months to determine whether remote memories are spared relative to more recent ones, as predicted by models of memory consolidation. At 3, 6 or 12 months of age, groups of rats received forced-choice training as to the location of food reward in a cross maze. At 12.5 months, rats received bilateral neurotoxic lesions to the hippocampus or a control surgical procedure and 2 weeks later their memory for the spatial location was tested. Their performance was compared to that of rats with hippocampal or control lesions with no prior training on several measures of savings. The hippocampal group with no pre-training, as expected, was severely impaired in learning the location of the food reward. Compared to this group, rats with hippocampal lesions that were pre-trained consistently performed better at the shortest training-surgery interval but not at the longer ones. That is, rats with hippocampal lesions exhibited retrograde amnesia at all training-surgery intervals and a forgetting curve that paralleled that of the control groups. The results were interpreted within a framework that distinguishes between relational and associative context, and as providing evidence that the hippocampus is necessary for the retention and retrieval of memories that are bound to relational context, regardless of the age of the memory.

Amnesia, Retrograde↗

Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway.

To study the physiological and molecular mechanisms of age-related memory loss, we assessed spatial memory in C57BL/B6 mice from different age cohorts and then measured in vitro the late phase of hippocampal long-term potentiation (L-LTP). Most young mice acquired the spatial task, whereas only a minority of aged mice did. Aged mice not only made significantly more errors but also exhibited greater individual differences. Slices from the hippocampus of aged mice exhibited significantly reduced L-LTP, and this was significantly and negatively correlated with errors in memory. Because L-LTP depends on cAMP activation, we examined whether drugs that enhanced cAMP would attenuate the L-LTP and memory defects. Both dopamine D1/D5 receptor agonists, which are positively coupled to adenylyl cyclase, and a cAMP phosphodiesterase inhibitor ameliorated the physiological as well as the memory defects, consistent with the idea that a cAMP-protein kinase A-dependent signaling pathway is defective in age-related spatial memory loss.

Aging↗

Differential effects of electroconvulsive shock on concurrent spatial memories: "old" memories are impaired while "new" memories are spared.

The effects of electroconvulsive shock (ECS) on spatial memory first reported by Shavalia, Dodge, and Beatty (1981, Behavioral and Neural Biology, 31, 261-273) were systematically replicated in two experiments. Rats acquired concurrent spatial memories in two 8-arm radial mazes. Each rat was allowed four choices in Maze 1 and then, after 2 h, four choices in Maze 2. After 2 h each rat was tested for retention in Maze 1 and, after 2 more h, was tested for retention in Maze 2. A single ECS was administered immediately after the fourth choice in Maze 2. Retention (as measured by accuracy of Choices 5-8) was diminished for Maze 1 but not for Maze 2. In the second experiment, the delay between the retention tests was eliminated (thus holding the ECS-Choice 5 interval constant for the two mazes). Once again retention of Maze 1 was impaired and retention of Maze 2 was spared; that finding suggests that ECS does not proactively affect radial-arm maze performance. The results of a third experiment converge on the same conclusion; ECS failed to reduce levels of spontaneous alternation. Therefore, ECS appears to interfere retroactively with relatively old spatial memories and newly established memories appear to be immune to the amnestic effects of ECS. Implications and various explanations are considered.

Animals↗

Lesions affecting the parahippocampal cortex yield spatial memory deficits in humans.

Anatomical studies in monkeys, and functional imaging and lesion studies in humans, suggest that, within the primate medial temporal neocortex, the parahippocampal cortex (PHC) is particularly involved in spatial tasks. However, evidence for a functional specialization of the PHC regarding its spatial memory functions has so far been lacking. Here, we investigated spatial memory functions of the human perirhinal cortex (PRC) and PHC. Patients with lesions affecting the PRC but sparing the PHC, and patients with lesions affecting both PRC and PHC, performed an oculomotor delayed response task with unpredictably varied memory delays of up to 30 s. Compared to controls, patients with PRC+PHC lesions showed a significant delay-dependent inaccuracy of memory-guided eye movements contralateral to the lesion side, whereas patients with PRC lesions showed no significant inaccuracy. Our results show that the PHC is a critical component for spatial memory in humans and suggest that (i) extrahippocampal spatial memory functions of the medial temporal lobe may not be equally distributed in the medial temporal neocortex, but may be largely confined to the PHC, and (ii) damage to connections between cortices involved in spatial cognition and rostral regions of the temporal lobe is unlikely to account for the observed spatial memory deficits with PHC lesions.

Adult↗

Prenatal exposure to ethanol disrupts spatial memory: effect of the training-testing delay period.

The present study investigated how variations in the period of delay between training and testing in the Morris water maze task affect the use of spatial memory in adult rats that were prenatally exposed to ethanol. Previous results utilizing the Morris water maze task have shown that prenatal, or early postnatal, exposure to ethanol produces deficits in the use of spatial memory, a type of memory that is dependent on an intact hippocampus. However, in these prior studies the delay period between the training of animals and the testing of spatial memory is typically fixed at only 1 day. In the current study, which utilized a revised training procedure within the Morris water maze task, the period of delay between training and testing was altered such that it was either 1 day or 3 days. Following the 3-day delay, different levels of prenatal exposure to ethanol impaired the use of spatial memory. In contrast, following the 1-day delay, prenatal exposure to ethanol failed to impair the use of spatial memory. The present study thus shows that prenatal exposure to ethanol differentially affects spatial memory in the Morris water maze task depending on the period of delay between training and testing.

Analysis of Variance↗

Spatial memory and instrumental conditioning.

Short-term spatial memory of rats was studied in a 12-arm radial tubular maze. Correct performance does not depend on maze structure which affects, however, the rat’s trajectory through the maze. Rats overtrained in the 12-arm radial maze show considerable transfer of the habit to a maze consisting of 12 parallel alleys entered from a common choice area. When isolated maze channels equipped with one way doors on both ends are randomly scattered over an enclosed area of 2 square meters the rats are capable of visiting them sequentially, even when they encounter this particular configuration for the first time. Rats which were allowed 6 choices in the 12-arm radial maze and were then transferred to linear configuration of the same maze channels do not show significant preference for the yet unvisited channels. This indicates that in absence of spatial cues other sensory properties of the different channels cannot guide the choice behavior of the animal. An essential prerequisite of spatial memory tests is elimination of cues which would allow direct sensory location of the baited alleys. Smelling the food hidden in the food-cups may significantly improve the rats performance unless the maze channels are saturated with food odor. It is concluded that a prerequisite for the striking performance of rats in the tasks of the above type is their thorough familiarization with the list of choices. The spatial location of an item is an important cue for the recognition of the choices already made.

Animals↗

Proposed neural circuitry for spatial memory in the primate brain.

The possible cerebral cortical circuitry for spatial memory in primates is discussed in light of a conceptual model and clinical as well as animal behavioral data. It is proposed that spatial memory formation begins with the arrival of sensory information in primary sensory areas and involves progressive elaboration through parasensory and higher-order association cortices. The connectivity between the association areas and the paralimbic and limbic regions is viewed as critical to the consolidation process. Finally, the execution of spatial behavior is presumed to involve the post-Rolandic and paralimbic projections to the frontal lobe. It is hoped that this conceptualization may provide a framework for further studies dealing with spatial memory.

Animals↗

[Improved alternative electro-stimulus Y-maze for evaluating the spatial memory of rats].

OBJECTIVE: To establish an effective model for evaluating the spatial memory of rats. METHODS: The adjacent left or right arm in Y-maze was defined as an initial arm or an objective one alternatively, and electro-stimulus to vola was used as a reinforcement. Meanwhile, the reliability of the model was validated by measuring the memory deficits induced by intraperitoneal (i.p.) injection of scopolamine (0.5 mg/kg) or bilaterally intrahippocampal (i.h.) microinjection of MK-801(0.2 microg/site). RESULTS: The normal, sham-operated or saline-treated rats learned the left-right alternative memory model rapidly while injection of either scopolamine or MK-801 caused spatial memory deficits in Y-maze, including deficits in working and reference memory. Moreover,there was no appreciable difference in electricity intensity between the treated group and the control group. CONCLUSION: The alternative Y-maze with electro-stimulus is a comparatively objective model which can evaluate the spatial memory in rats effectively.T

Animals↗

Memory for targets in a multilevel simulated environment: evidence for vertical asymmetry in spatial memory.

In two experiments, adult participants explored a symmetrical three-tiered computer-simulated building that contained six distinctive objects, two on each floor. Following exploration, the objects were removed, and the participants were asked to make direction judgments from each floor, indicating the former positions of the objects on that floor and on higher and lower floors. Relative tilt error scores indicated a bias, in that targets that were higher than the test location were judged as consistently lower than their actual positions and targets that were lower than the test location were judged as consistently higher than their actual positions. Absolute tilt errors revealed an asymmetry, with more accurate and less variable tilt errors for judgments directed to lower floors than for judgments directed to higher floors. Experiment 3 ruled out an account of the findings that does not relate them to spatial memory. The results suggest that the superiority of downward over upward spatial judgments, previously reported in two-dimensional visual-spatial tasks, extends to navigational spatial memory.

Adolescent↗

The Nine Box Maze Test: A measure of spatial memory development in children.

This study investigates the development of visuo-spatial memory in school-aged children, as measured by the Nine Box Maze Test Child Version (NBMT-CV). This task, originally developed for adults by, utilises an allocentric framework to assess the complexities of spatial memory. Sixty children participated in this study (aged 5-12 years), which also involved administration of traditional 'non-verbal' memory tests. Results indicate that visuo-spatial memory develops across childhood and that the NBMT-CV taps distinct skills compared to other 'non-verbal' memory tasks. The theoretical, assessment and developmental issues raised by these findings are discussed.

Child↗

Effects of medial and dorsal cortex lesions on spatial memory in lizards.

In mammals and birds, the hippocampus is a major learning and memory center that plays a prominent role in spatial memory, the use of distal cues to guide navigation. The role of reptilian hippocampal homologues, the medial and dorsal cortex, in spatial memory has not been thoroughly investigated. The medial and dorsal cortex of reptiles is known to play a role in learning both tasks that are hippocampally dependent and tasks that are not hippocampally dependent in mammals and birds. In order to examine the specific role of the medial and dorsal cortex in spatial memory, we trained medial cortex, dorsal cortex, and sham lesioned Cnemidophorus inornatus lizards to locate the one heated rock of four identical rocks spaced evenly around the perimeter of a circular, sand filled, arena in a cool room. We used probe trials to examine the strategies used by lizards to locate the goal. Medial cortex lesions and dorsal cortex lesions slowed acquisition and altered the strategies used to locate the goal. However, none of the lizards adopted a spatial strategy to locate the goal suggesting that the dorsal cortex and medial cortex are involved in using non-spatial strategies for navigation.

Animals↗

Methylphenidate improves visual-spatial memory in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: To investigate the effect of methylphenidate (MPH) on visual-spatial memory, as measured by subtests of the Cambridge Neuropsychological Testing Automated Battery (CANTAB), in children with attention-deficit/hyperactivity disorder (ADHD). Visual-spatial memory is a core component of working memory that has been shown to be impaired in ADHD, irrespective of comorbid reading and/or language problems. METHOD: A clinic-referred sample of school-age children with a confirmed DSM-IV diagnosis of ADHD (n = 26) completed tests of visual-spatial memory, planning ability, and recognition memory in an acute, randomized, placebo-controlled, crossover trial with three single fixed doses of MPH. MPH effects on right-handed and left-handed motor control were also assessed. RESULTS: MPH significantly improved performance on a self-ordered, updating visual-spatial working memory task and on maintenance of visual-spatial information but had no effects on measures of visual-spatial planning ability or recognition memory. Also, MPH significantly improved left-handed motor control. CONCLUSIONS: Beneficial effects of MPH on visual-spatial processing in ADHD are selective and restricted to visual-spatial memory.

Attention Deficit Disorder with Hyperactivity↗