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Results for “Spatial memory”

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PubMed2004

Effect of the histamine H3-antagonist clobenpropit on spatial memory deficits induced by MK-801 as evaluated by radial maze in Sprague-Dawley rats.

This study was performed to investigate whether or not the histamine H3-antagonist clobenpropit can ameliorate spatial memory deficits induced by MK-801 (0.3 microg per site) as evaluated by an eight-arm radial maze task of rats. A bilateral intrahippocampal (i.h.) injection of clobenpropit (5, 10 microg per site, dose-dependent) markedly improved the working and reference memory deficits induced by MK-801. Its ameliorating effect was potentiated by histidine, but completely antagonized by immepip (2.5 microg per site), a selective H3-agonist. alpha-Fluoromethylhistidine (FMH, 25 microg per site), a selective histidine decarboxylase inhibitor prevented the ameliorating effect of clobenpropit on the working memory deficits induced by MK-801. In addition, the H(1-antagonist pyrilamine, but not the H2-antagonist cimetidine, also inhibited the procognitive effects of clobenpropit. Both FMH and pyrilamine did not significantly modulate the effect of clobenpropit on reference memory. Therefore, the results of this study suggest that the procognitive effects of clobenpropit in MK-801-induced working memory deficits is mediated by increasing endogenous histamine release. In addition, the ameliorating effect of clobenpropit on reference memory might be due to the increased release of neurotransmitters other than histamine.

Analysis of Variance↗

PubMed1984

Age-dependent deficits in spatial memory are related to impaired hippocampal kindling.

Fischer 344 rats, 3 and 26 months of age, were first tested in an eight-arm spatial maze to assess memory function behaviorally. The same animals were then subjected to hippocampal kindling to examine alterations in neuronal plasticity as a function of aging. The results indicated that spatial memory was poorer and hippocampal kindling slower in aged rats than in young ones. Furthermore, there was a striking positive relation between performance in the eight-arm spatial maze and speed of kindling. This finding suggests that age-related deficits in spatial memory and hippocampal kindling reflect decreased efficacy of synaptic transmission in a common neuroanatomical substrate.

Aging↗

PubMed2003

Effect of chronic stress on spatial memory in rats is attenuated by lithium treatment.

Stress is known to alter cognitive functions, such as memory, and it has been linked to the pathophysiology of mood and anxiety disorders. Chronic lithium treatment is used in some psychiatric disorders and has been suggested to act upon mechanisms which can enhance neuronal viability. The purpose of this work is to investigate a possible effect of lithium treatment in a chronic stress model. Adult male Wistar rats were divided in two groups, control and chronically stressed, treated either with normal chow or with chow containing LiCl for 40 days. Stress treatment was a chronic variable stress model, consisting of different stressors which were applied in a random fashion, once a day, every day. Memory was assessed by using the water maze task. The results demonstrated a marked decrease in reference memory in the water maze task in chronically stressed rats. This effect was attenuated by lithium treatment in all the parameters considered. No effect was observed in the working memory. These results indicate that lithium treatment may counteract some effects of chronic stress situations, particularly concerning spatial memory.

Animals↗

PubMedDate not supplied

Training, transfer, and retention of three-dimensional spatial memory in virtual environments.

Human orientation requires one to remember and visualize spatial arrangements of landmarks from different perspectives. Astronauts have reported difficulties remembering relationships between environmental landmarks when imagined in arbitrary 3D orientations. The present study investigated the effects of strategy training on humans' 1) ability to infer their orientation from landmarks presented ahead and below, 2) performance when subsequently learning a different array, and 3) retention of configurational knowledge over time. On the first experiment day, 24 subjects were tested in a virtual cubic chamber in which a picture of an animal was drawn on each wall. Through trial-by-trial exposures, they had to memorize the spatial relationships among the six pictures around them and learn to predict the direction to a specific picture when facing any view direction, and in any roll orientation. Half of the subjects ("strategy group") were taught methods for remembering picture groupings, while the remainder received no such training ("control group"). After learning one picture array, the procedure was repeated in a second. Accuracy (% correct) and response time learning curves were measured. Performance for the second array and configurational memory of both arrays were also retested 1, 7, and 30 days later. Results showed that subjects "learned how to learn" this generic 3D spatial memory task regardless of their relative orientation to the environment, that ability and configurational knowledge was retained for at least a month, that figure rotation ability and field independence correlate with performance, and that teaching subjects specific strategies in advance significantly improves performance. Training astronauts to perform a similar generic 3D spatial memory task, and suggesting strategies in advance, may help them orient in three dimensions.

Adolescent↗

PubMed1990

Organizational effects of early gonadal secretions on sexual differentiation in spatial memory.

Neonatally castrated (MNC) and control male rats (MC) and female rats treated neonatally with estradiol benzoate (FNE) and female controls (FC) were studied. In Exp. 1 spatial memory was assessed using a 12-arm radial maze. During acquisition, MC and FNE groups were more accurate in choice behavior than FC and MNC groups. In Exp. 2 the discriminative control exerted by different types of cues was evaluated. Alteration of the geometry of the room but not movable landmarks disrupted performance of MC and FNE groups. For the FC and MNC groups, alteration of either geometry or landmarks did not disrupt performance. In Exp. 3 the effect of a 15-min delay was determined. MC and FNE groups were more disrupted by a delay than MNC and FC groups. Together, these data suggest that early exposure to gonadal steroids (probably estradiol) improves acquisition of spatial tasks by reorganizing and simplifying associational-perceptual processes that guide spatial ability.

Animals↗

PubMed2002

The neurosteroid pregnenolone sulfate infused into the medial septum nucleus increases hippocampal acetylcholine and spatial memory in rats.

The effects of an infusion of the neurosteroid pregnenolone sulfate into the medial septum on acetylcholine release in the hippocampus and on spatial memory were evaluated in two experiments. Results show that pregnenolone sulfate enhanced acetylcholine release by more than 50% of baseline and improved recognition memory of a familiar environment. Therefore, our results suggest that the septo-hippocampal pathway could be involved in the promnesic properties of this neurosteroid.

Acetylcholine↗

PubMed2006

Impaired allocentric spatial memory underlying topographical disorientation.

The cognitive processes supporting spatial navigation are considered in the context of a patient (CF) with possible very early Alzheimer's disease who presents with topographical disorientation. Her verbal memory and her recognition memory for unknown buildings, landmarks and outdoor scenes was intact, although she showed an impairment in face processing. By contrast, her navigational ability, quantitatively assessed within a small virtual reality (VR) town, was significantly impaired. Interestingly, she showed a selective impairment in a VR object-location memory test whenever her viewpoint was shifted between presentation and test, but not when tested from the same viewpoint. We suggest that a specific impairment in locating objects relative to the environment rather than relative to the perceived viewpoint (i.e. allocentric rather than egocentric spatial memory) underlies her topographical disorientation. We discuss the likely neural bases of this deficit in the light of related studies in humans and animals, focusing on the hippocampus and related areas. The specificity of our test indicates a new way of assessing topographical disorientation, with possible application to the assessment of progressive dementias such as Alzheimer's disease.

Activities of Daily Living↗

PubMed1993

Attenuation of scopolamine-induced spatial memory deficits in the rat by cholinomimetic and non-cholinomimetic drugs using a novel task in the 12-arm radial maze.

The effects of cholinomimetic and non-cholinomimetic agents on spatial memory using a novel task in the 12-arm radial maze were investigated. The task was designed to reduce the tendency to use non-spatial strategies. Animals were repeatedly trained to retrieve food rewards from three arms, until a criterion level of performance was reached. Scopolamine (0.03 and 0.1 mg/kg SC), but not N-methylscopolamine (0.1 mg/kg SC) disrupted performance of this task. Physostigmine (0.3 mg/kg SC) and pilocarpine (30 mg/kg SC) completely reversed the deficit of performance produced by scopolamine. Furthermore, the ACE inhibitor Hoe 288 (10 nmol ICV) and the angiotensin AT1 receptor antagonist losartan (10 mg/kg SC) also significantly attenuated the scopolamine-induced deficit. These results show that this novel task in the radial maze is sensitive to the disruptive effects of scopolamine and can identify cognitive enhancing effects of both cholinomimetic and non-cholinomimetic drugs. Thus, this maze task provides a useful model for the evaluation of novel cognitive enhancing agents.

Angiotensin Receptor Antagonists↗

PubMed2006

Effects of overexpression of Sim2 on spatial memory and expression of synapsin I in rat hippocampus.

The single-minded 2 gene (Sim2) plays a crucial role in the mental retardation of Down Syndrome (DS). To explore how Sim2 influences spatial memory, a DNA plasmid-encoding mouse Sim2 (mSim2) wrapped with liposome was bilaterally injected into the hippocampus of rats. The effect of overexpressing mSim2 on spatial learning was determined by a Morris water maze task. The expression of synapsin I was detected by reverse transcriptional-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry, respectively. The phosphosynapsin was also examined by immunohistochemistry. As demonstrated by RT-PCR, mSim2 was overexpressed in the hippocampus of rats, and pcDNA3/mSim2-transfected rats showed longer latency to find the hidden platform compared with pcDNA3-transfected rats (P<0.05). Synapsin I mRNA and protein expression were decreased significantly by mSim2 transfection, as demonstrated by RT-PCR and immunohistochemistry. Moreover, the expression profile of phosphosynapsin was similar to that of synapsin I. So it is concluded that Sim2 could impair the ability of learning and memory by inhibiting synaptic plasticity, and may play a crucial role in the pathogenesis of DS.

Animals↗

PubMed1999

Choline supplementation during prenatal development reduces proactive interference in spatial memory.

Previous research has demonstrated that increasing dietary choline during early development can have long-lasting effects on cholinergic (Ch) function that are correlated with improvement of spatial memory ability in rats. The present study is designed to further our understanding of these organizational changes in brain and behavior by examining the effects of spaced vs. massed trials. A third of the rats (n=10) were supplemented with choline chloride prenatally by adding it to the drinking water of their dams. Another third were made deficient of choline during early development by removing choline from the dams diet. The remaining rats served as untreated controls. Postnatally, the offspring were maintained on a choline-sufficient diet and at 120 days of age they began 12-arm radial maze training. The maze data revealed two major effects of early choline availability: (1) Both choline-supplemented and choline-deficient rats performed more accurately than control littermates when trials were spaced. These differences in spatial ability did not appear to be a function of differential response or cue-use strategies. (2) Choline-supplemented rats showed little proactive interference when trials were massed; whereas control rats demonstrated moderate levels and choline-deficient rats exhibited high levels of proactive interference as a function of massed trials. These data suggest that the behavioral consequences of early dietary availability of choline may involve the modification of the discriminative abilities used to attend to stimuli that demarcate the end of one trial and the start of another as well as the capacity for remembering the locations that have been visited during a trial.

Animals↗

PubMed2005

Influence of prenatal noise and music on the spatial memory and neurogenesis in the hippocampus of developing rats.

During the prenatal period, the development of individual is influenced by the environmental factors. In the present study, the influence of prenatal noise and music on the spatial memory and neurogenesis in the hippocampus of developing rats was investigated. The exposure to the noise during pregnancy caused growth retardation, decreased neurogenesis in the hippocampus, and impaired spatial learning ability in pups. The exposure to music during pregnancy, on the other hand, caused increased neurogenesis in the hippocampus and enhanced spatial learning ability in pups. The present study has shown the importance of the prenatal environmental conditions for the cognition and brain development.

Animals↗

PubMed2002

Cholinergic receptor blockade in prefrontal cortex and lesions of the nucleus basalis: implications for allocentric and egocentric spatial memory in rats.

In this study we have examined the involvement of the prefrontal cortex (PFC) along with the Nucleus basalis magnocellularis (NBM) in two types of spatial navigation tasks. We evaluated the effects of excitotoxic (ibotenate-induced) lesions of the NBM in an allocentric and an egocentric task in the Morris water maze, using sham operations for a comparison. In both cases we also assessed the effects of local cholinergic receptor blockade in the PFC by infusing the muscarinic receptor antagonist scopolamine (4 or 20 microg). Anatomically, the results obtained showed that this lesion produced a profound loss of acetylcholinesterase (AChE) positive cells in the NBM, and a loss of AChE positive fibres in most of the neocortex, but hardly in the medial PFC. Behaviourally, such lesions led to a severe impairment in the allocentric task. Intraprefrontal infusions of scopolamine led to a short-lasting impairment in task performance when the high dose was used. In the second experiment, using the same surgical manipulations, we examined the performance in the egocentric task. Like in the allocentric task animals with NBM lesions were also impaired, but with continued training they acquired a level of performance similar to the sham-operated ones. This time, infusions of scopolamine in the medial PFC led to a severe disruption of performance in both groups of animals. We conclude that acetylcholine in the medial PFC is important for egocentric but not allocentric spatial memory, whereas the NBM is involved in the learning of both tasks, be it to a different degree.

Acetylcholinesterase↗

PubMed2004

Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats.

BACKGROUND: The authors demonstrated previously that isoflurane-nitrous oxide anesthesia attenuates performance improvement on an already-learned spatial memory task and that the effect persists for weeks. This experiment was designed to test the hypothesis that learning of new information is particularly susceptible to prolonged disruption after general anesthesia. METHODS: Six- (n = 5) and 20- (n = 5) month-old male Fischer 344 rats were anesthetized for 2 h with 1.2% isoflurane, 70% nitrous oxide, and 30% oxygen. Age-matched control rats received 30% oxygen and 70% nitrogen (n = 5 per group). Rats breathed spontaneously, and anesthetic and oxygen concentrations were measured. Spatial learning was assessed daily for 21 days on a 12-arm radial maze (RAM) beginning 48 h after anesthesia. In a post hoc experiment to examine locomotion, swim speed was assessed in a separate group of identically treated rats (n = 3 per group) for 4 days beginning 48 h after anesthesia. RESULTS: Aged rats were slower to complete the maze, made fewer correct choices before first error, and made more errors at baseline than young rats (P < 0.05). Anesthesia worsened maze performance in both age groups, as evidenced by increased time to complete the maze and a decreased number of correct choices before first error (P < 0.05), but there were no statistically significant differences in total number of errors. Interestingly, there were no age-by-anesthesia interactions. Aged rats swam slower than adult rats (P < 0.001), but there were no differences between the control and anesthesia groups. CONCLUSIONS: Isoflurane-nitrous oxide anesthesia is associated with a persistent deficit in RAM performance that is not explained by impaired locomotion. This impairment occurs in adult and aged rats, indicating that it is not an age-specific phenomenon. Thus, RAM performance is altered after general anesthesia for longer than predicted by the pharmacology of the drugs used, which, by inference, suggests a long-term deficit in learning/memory.

Aging↗

PubMed2005

Impaired remote spatial memory after hippocampal lesions despite extensive training beginning early in life.

Damage to the hippocampus typically produces temporally graded retrograde amnesia, whereby memories acquired recently are impaired more than memories acquired remotely. This phenomenon has been demonstrated repeatedly in a variety of species and tasks, and it has figured prominently in theoretical treatments of memory and hippocampal function. A striking exception to the finding of temporally graded retrograde amnesia comes from studies with rodents using spatial tasks like the water maze. In these studies, recent and remote memory were similarly impaired following hippocampal lesions. In contrast to work with rodents, studies of patients with medial temporal lobe lesions, including complete hippocampal lesions, indicate that remote spatial memory can be intact. One difference between studies in humans and studies in rodents is that spatial memory in animal studies is acquired during a limited period of time when the animals are adults. In contrast, the spatial memory studied in humans was acquired beginning at an early age and learning continued for a considerable period of time. We initiated training in a standard water maze immediately after rats had been weaned at 21 days of age and continued training until the rats were young adults (90 days old). Large hippocampal lesions were made 100 days after the completion of training. After recovery from surgery, control rats exhibited good retention on the first retention probe trial, but rats with hippocampal lesions performed at chance. Thus, even after extended training beginning early in life, and with a prolonged training-surgery interval, hippocampal lesions impair performance in the water maze task. Possible reasons for these findings are discussed in the context of the specific performance requirements of the water maze task.

Aging↗

PubMed2000

NGF gene transfer to intrinsic basal forebrain neurons increases cholinergic cell size and protects from age-related, spatial memory deficits in middle-aged rats.

Administration of nerve growth factor (NGF) by intracerebroventricular infusion or transplantation of NGF-secreting cells to the basal forebrain improves spatial memory in aged animals. Using the adeno-associated virus (AAV) vector system, basal forebrain neurons were transduced to produce NGF ectopically for long intervals (at least 9 months). Rats received intraseptal injections of either the control vector, pTR-UF4, or the pTR-NGFmyc at 3 months of age, prior to testing their performance in the Morris water task. An age-related decrease in the acquisition of the hidden platform location was found at 12 months of age in the pTR-UF4 control group, but not in the pTR-NGFmyc group. Further, when compared to 3 month old untreated animals, the control group, but not the pTR-NGFmyc group, was impaired at 12 months of age. Concomitant to preventing age-related memory deficits, the NGF gene transfer increased cholinergic neuron size by 34% in the medial septum. This approach may therefore represent a viable therapy for age-related dementia involving dysfunction in cholinergic activity and memory, such as Alzheimer's disease.

Aging↗

PubMed2005

Co-activation of glutamate and dopamine receptors within the nucleus accumbens is required for spatial memory consolidation in mice.

RATIONALE: The nucleus accumbens receives glutamatergic and dopaminergic inputs converging onto common dendrites. Recent behavioral data demonstrated that intra-accumbens administrations of either glutamate or dopamine (DA) antagonist impair spatial memory consolidation. Thus, also based on the biochemical and molecular findings demonstrating interactions among the different receptors subtypes for glutamate and dopamine, it is conceivable that memory consolidation within this structure might be modulated by glutamate-dopamine receptor interactions. OBJECTIVES: The purpose of this study was to examine the effects of intra-accumbens co-administrations of glutamate and DA antagonists on the consolidation of spatial information. METHODS: On day 1, CD1 male mice were placed in an open field containing five different objects and immediately after three sessions of habituation the animals were injected intra-accumbens with either vehicle or low doses of the N-methyl-D: -aspartate (NMDA; AP-5 50 ng/side), the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; DNQX 5 ng/side), the D1 (SCH23390 12.5 ng/side) and the D2 (sulpiride 25 ng/side) antagonists that were ineffective alone in disrupting object displacement. Separate groups were then focally injected with a combination of one of the glutamate antagonists with one of the dopamine antagonists. Twenty-four hours later, the ability of mice to discriminate object displacement was assessed. RESULTS: Controls and mice injected with ineffective doses of the NMDA, the AMPA, the D1 or the D2 antagonists were always able to react to the object displacement. On the contrary, the groups administered with the different combinations (AP-5 and SCH23390, AP-5 and sulpiride, DNQX and SCH23390, DNQX and sulpiride) of glutamate and dopamine antagonists did not discriminate the spatial change. CONCLUSIONS: These results demonstrate that glutamate-dopamine receptor interactions within the accumbens are essential for the consolidation process of spatial information.

2-Amino-5-phosphonovalerate↗

PubMed1984

Facilitated reversal learning of a spatial-memory task by medial septal injections of 6-hydroxydopamine.

To assess the role of hippocampal norepinephrine in learning and memory, rats were treated with medial septal injections of 6-hydroxydopamine either prior to or after acquisition of a spatial-memory task. No effect on acquisition learning or retention was observed. However, reversal learning was significantly enhanced in all treated animals regardless of whether treatment was prior to or after acquisition. Our results do not support a role of hippocampal norepinephrine in selective attention, but rather indicate a direct involvement in memory processes.

Animals↗

PubMed2000

Postnatal intracerebroventricular administrations of NGF alter spatial memory in adulthood.

The present work assessed the effects of intracerebroventricular injections (2x5 mg/2.5 ml) of recombined human nerve growth factor (rhNGF) at postnatal days 2 and 3 upon the development of spatial learning capacities in rats. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and reducing attention to the distant spatial cues. At the age of 2 months all the rats were retrained in the same task. Treatment effects were found in both immature and adult rats. The injection of NGF induced a slight alteration of the immature rats' performance. In contrast, a marked impairment of spatial abilities was shown in the 2-month-old rats. The most consistent effects were a significant increase in the escape latency and a decrease bias towards the training platform area during probe trials. The reduction of spatial memory was particularly marked if the subjects had been trained in a cued condition. Taken together, these experiments reveal that an acute pharmacological treatment that leads to transient modifications during early development might induce a behavioural change long after treatment. Thus, the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures that could be altered by precocious NGF administrations.

Aging↗