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PubMed2002

Reversible inhibition of CREB/ATF transcription factors in region CA1 of the dorsal hippocampus disrupts hippocampus-dependent spatial memory.

CREB is critical for long-lasting synaptic and behavioral plasticity in invertebrates. Its role in the mammalian hippocampus is less clear. We have interfered with CREB family transcription factors in region CA1 of the dorsal hippocampus. This impairs learning in the Morris water maze, which specifically requires the dorsal hippocampus, but not context conditioning, which does not. The deficit is specific to long-term memory, as shown in an object recognition task. Several forms of late-phase LTP are normal, but forskolin-induced and dopamine-regulated potentiation are disrupted. These experiments represent the first targeting of the dorsal hippocampus in genetically modified mice and confirm a role for CREB in hippocampus-dependent learning. Nevertheless, they suggest that some experimental forms of plasticity bypass the requirement for CREB.

Activating Transcription Factor 1↗
PubMed2003

Effect of the postictal state on visual-spatial memory in immature rats.

Postictal cognitive impairment following seizures can last from minutes to days and be disabling to the patient. The purpose of this study was to compare the behavioral features of seizures with postictal memory impairment in young seizure-naive rats and rats with a prior history of status epilepticus (SE) and examine the relationship between postictal EEG changes and cognitive recovery. Following training in the water maze to asymptote levels of learning, rats with a prior history of SE and seizure-naive rats had flurothyl-induced generalized seizures and time to recovery to baseline was then measured. Following generalized seizures rats had impaired performance in the water maze with the duration of the cognitive deficits exceeding the length of the seizure. There was not a close relationship between duration of cognitive impairment and either latency to onset of seizure or duration. The animal's neurological status was a factor in the duration of cognitive impairment following seizures; while there were no differences between SE and seizure-naive rats in latency to seizure onset or duration of the seizures, animals with a prior history of SE had a longer period of impairment following a seizure than animals without such a history. Postictal cognitive impairment was associated with changes in theta activity in animals with a prior history of SEs but not in seizure-naive animals. Caffeine, when administered following the seizure, reduced postictal cognitive impairment in a dose-dependent manner. This study demonstrates that duration of postictal cognitive impairment is not directly related to duration of the seizure. The neurological status of the animal is a determining factor in duration of postictal impairment.

Animals↗
PubMed2002

The role of self-to-object updating in orientation-free performance on spatial-memory tasks.

A single view of a room-sized path produces an orientation-specific memory representation, yet when memory is tested at a location on the path, orientation-free performance is observed. Either a virtual-views or an updating hypothesis can account for orientation-free performance by attributing it, respectively, to an orientation-free long-term-memory representation or to a working-memory representation of the body's updated location relative to the path. Experiments 1 and 2 test these hypotheses by manipulating the test-site location and the complexity of the trajectory from the study site to the test site. Experiment 3 tests orientation to the test space as a function of trajectory complexity. Results support a virtual-views explanation for the orientation-free performance of males and an updating explanation for females.

Adolescent↗
PubMed1988

Parallel modifications of spatial memory performances, exploration patterns, and hippocampal theta rhythms in fornix-damaged rats: reversal by oxotremorine.

Learning scores and degrees of divergence of the exploratory patterns (EP) displayed during the acquisition stage of a radial eight-arm maze task were examined in fornix-damaged and sham-operated rats injected either with oxotremorine (0.1 mg/kg) or saline. Modifications of hippocampal rhythmic slow activity (theta) recorded in each condition were analyzed in CA1 and dentate gyrus. Dorsal fornix sections reduced choice accuracy but also induced the adoption of weakly divergent EP. Oxotremorine in animals with lesions reinstates both learning scores and degree of divergence of EP at the levels respectively observed in saline sham-operated animals. Finally, oxotremorine in sham-operated animals did not significantly improve choice accuracy but strongly modified the EP. Preoperatively, theta rhythms indicated a decrease of frequency after oxotremorine administration. Postoperatively, they showed an increase of frequency in animals with lesions that were reinstated at the preoperative level by oxotremorine.

Animals↗
PubMed1996

Effects of lesions of the associative parietal cortex on the acquisition and use of spatial memory in egocentric and allocentric navigation tasks in the rat.

It has been hypothesized that the rat associative parietal cortex (APC) is involved in the association between visuospatial and locomotion-generated (kinesthetic) information. To study the kinesthetic component, APC-lesioned and control rats were trained in total darkness to reach a submerged platform in the Morris water maze. In the egocentric task, the relative position of the starting point and the platform was constant all over training. Parietal rats have been found impaired in acquisition and to a less extent in retention of this task. In the allocentric task, rats were then trained in the standard version of the navigation task. A mild deficit was observed in acquisition of this task because the APC-lesioned rats displayed longer escape latencies but control-like search patterns. These results suggest that the APC is involved in the coding of kinesthetic information that plays an important role in place navigation.

Animals↗
PubMed1985

Role of noradrenergic function in the opiate antagonist facilitation of spatial memory.

Animals previously trained to criterion on an eight-arm radial maze task received either bilateral 6-hydroxydopamine lesions of the dorsal noradrenergic bundle (DNB) or control surgery. Following a 3-week recovery period, the animals were trained on the same radial maze in two novel environments. By a within-subjects design, in one of these environments animals received posttraining systemic treatment with the opiate antagonist naloxone; in the other novel environment, they received vehicle injection. In animals that received control surgery, opiate antagonist treatment produced a reliable enhancement of performance. Although the DNB-lesion animals did not differ from the control-surgery animals under the saline treatment condition, denervation of forebrain norepinephrine (NE) was found to prevent the memory enhancing effect of posttraining naloxone administration. These results provide further support that enhanced retention obtained with opiate antagonist administration is dependent upon intact NE function.

Animals↗
PubMed1977

Spatial memory.

Explore the source record for details and available documents.

Action Potentials↗
PubMed1996

Long-term functional recovery from age-induced spatial memory impairments by nerve growth factor gene transfer to the rat basal forebrain.

Nerve growth factor (NGF) stimulates functional recovery from cognitive impairments associated with aging, either when administered as a purified protein or by means of gene transfer to the basal forebrain. Because gene transfer procedures need to be tested in long-term experimental paradigms to assess their in vivo efficiency, we have used ex vivo experimental gene therapy to provide local delivery of NGF to the aged rat brain over a period of 2.5 months by transplanting immortalized central nervous system-derived neural stem cells genetically engineered to secrete NGF. By grafting them at two independent locations in the basal forebrain, medial septum and nucleus basalis magnocellularis, we show that functional recovery as assessed in the Morris water maze can be achieved by neurotrophic stimulation of any of these cholinergic cell groups. Moreover, the cholinergic neurons in the grafted regions showed a hypertrophic response resulting in a reversal of the age-associated atrophy seen in the learning-impaired aged control rats. Long-term expression of the transgene lead to an increased NGF tissue content (as determined by NGF-ELISA) in the transplanted regions up to at least 10 weeks after grafting. We conclude that the gene transfer procedure used here is efficient to provide the brain with a long-lasting local supply of exogenous NGF, induces long-term functional recovery of cognitive functions, and that independent trophic stimulation of the medial septum or nucleus basalis magnocellularis has similar consequences at the behavioral level.

Aging↗
PubMed1999

One-year study of spatial memory performance, brain morphology, and cholinergic markers after moderate controlled cortical impact in rats.

Persistent cognitive deficits are one of the most important sequelae of head injury in humans. In an effort to model some of the structural and neuropharmacological changes that occur in chronic postinjury brains, we examined the longitudinal effects of moderate vertical controlled cortical impact (CCI) on place learning and memory using the Morris water maze (MWM) test, morphology, and vesicular acetylcholine (ACh) transporter (VAChT) and muscarinic receptor subtype 2 (M2) immunohistochemistry. Vertical CCI (left parietal cortex, 4 m/sec, 2.5 mm; n = 10) or craniotomy (sham) was produced in male Sprague-Dawley rats (n = 10). Place learning was tested at 2 weeks, 4 weeks, 3 months, 6 months, and 12 months postinjury with the escape platform in a different maze quadrant for each time point. At each interval, rats received 5 days of water maze acquisition (latency to find hidden platform), a probe trial to measure place memory, and 2 days of visible platform trials to control for nonspecific deficits. At 3 weeks, half the animals were sacrificed for histology. At these injury parameters, CCI produced no significant differences in place learning between injured and sham rats at 2 weeks, 4 weeks, or 6 months after injury. However, at 3 and 12 months, the injured rats took significantly longer to find the hidden platform than the sham rats. Probe trial performance differed only at 12 months postinjury between injured (25.73+/-2.1%, standard error of the mean) and sham rats (44.09+/-7.0%, p < 0.05). The maze deficits at 1 year were not due to a worsening of performance, but may have resulted from a reduced ability of injured rats to benefit from previous water maze experience. Hemispheric loss of 30.4+/-5.5 mm3 was seen at 3 weeks after injury (versus respective sham). However, hemispheric loss almost doubled by 1 year after injury (51.5+/-8.5 mm3, p < 0.05 versus all other groups). Progressive tissue loss was also reflected by a three- to fourfold increase in ipsilateral ventricular volume between 3 weeks and 1 year after injury. At 1 year after injury, immunostaining for VAChT was dramatically increased in all sectors of the hippocampus and cortex after injury. Muscarinic receptor subtype 2 (M2) immunoreactivity was dramatically decreased in the ipsilateral hippocampus. This suggests a compensatory response of cholinergic neurons to increase the efficiency of ACh neurotransmission. Moderate CCI in rats produces subtle MWM performance deficits accompanied by persistent alteration in M2 and VAChT immunohistochemistry and progressive tissue atrophy. The inability of injured rats to benefit from repeated exposures to the MWM may represent a deficit in procedural memory that is independent of changes in hippocampal cholinergic systems.

Analysis of Variance↗
PubMed1986

Adult age differences in spatial memory: effects of distinctiveness and repeated experience.

Young (mean age = 25.0) and elderly (mean age = 65.0) women's memory for buildings in a large model town was assessed. Participants viewed and constructed the town on two trials. Building distinctiveness was manipulated by showing differentiated buildings with unique physical and functional properties (e.g., school, gas station), or nondifferentiated buildings that were not functionally distinct and only somewhat physically distinct (e.g., red cube-like structure with curved roof, yellow cube-like structure with flat roof). Building distinctiveness was further manipulated by verbally labeling or not labeling each building type. On Trial 1 young adults were more accurate than elderly adults only on the differentiated buildings; on Trial 2 this age difference was evident on differentiated and nondifferentiated buildings. Verbal labeling did not significantly affect construction accuracy. It was concluded that age differences occurred because elderly adults have more difficulty utilizing encoding strategies than young adults.

Adult↗
PubMed1994

Impaired spatial memory in aged rats is associated with alterations in inositol phospholipid metabolism.

WE have investigated changes in inositol phospholipid turnover and membrane arachidonic acid concentration in the dentate gyrus and frontal cortex of animals aged 3-6 months, 14 months or 22 months which were trained in the Morris water maze. Ageing was associated with poorer performances in the behavioural test, characterized by increased variability in retention and acquisition amongst individuals, a decrease in membrane arachidonic acid concentration and increased unstimulated inositol phospholipid metabolism in synaptosomes prepared from frontal cortex and dentate gyrus. Arachidonic acid stimulated inositol phospholipid metabolism in synaptosomes, but in the older groups, stimulation was associated with good performance in the Morris water maze. In slices prepared from frontal cortex, responsiveness of inositol phospholipid metabolism to glutamate was also age- and performance-dependent. The findings highlight a correlation between age, inositol phospholipid metabolism and performance in the Morris water maze.

Aging↗
PubMed1997

Perinatal choline supplementation increases the threshold for chunking in spatial memory.

Chunking and perinatal choline supplementation each provide rats with alternative memory processing advantages. Evidence from radial-arm maze performance of adult (2- to 5-month-old) rats indicates that chunking of multiple food types (sunflower seeds, Noyes pellets and rice puffs) emerges for stable, differentiable baiting patterns as a function of the memory load (6, 12, 18 or 24 maze arms). The number of maze arms appeared to determine both the level of task difficulty at which rats began to implement a chunking strategy as well as when they were unable to successfully implement such a strategy due to the excess memorial demands of the task. In comparison to control rats, rats treated perinatally with choline supplementation displayed a horizontal rightward shift of the response function that related level of clustering of like-food types to the number of maze arms. These results indicate a higher threshold for implementing a chunking strategy in rats treated perinatally with choline supplementation, possibly due to a choline-induced increase in memory capacity.

Animals↗
PubMedDate not supplied

Tests of a dynamic systems account of the A-not-B error: the influence of prior experience on the spatial memory abilities of two-year-olds.

Recently, Smith, Thelen, and colleagues proposed a dynamic systems account of the Piagetian "A-not-B" error in which infants' errors result from general processes that make goal-directed actions to remembered locations. Based on this account, the A-not-B error should be a general phenomenon, observable in different tasks and at different points in development. Smith, Thelen, et al.'s proposal was tested using an A-not-B version of a sandbox task. During three training trials and three "A" trials, 2-year-olds watched as a toy was buried in a sandbox at Location A. Following a 10-s delay, children searched for the object. Across five experiments, children's (total N = 92) performance on the A trials was accurate. After the A trials, children watched as a toy was hidden at Location B, 8 to 10 inches from Location A. In all experiments, children's searches after a 10-s delay were significantly biased in the direction of Location A. Furthermore, this bias toward Location A decreased with repeated trials to Location B, as well as when children completed fewer trials to Location A. Together, these data suggest that A-not-B-type errors are pervasive across tasks and development.

Child Development↗
PubMed1994

Does neuronal damage of CA1 relate to spatial memory performance of rats subjected to transient forebrain ischemia?

The effect of ischemia-induced hippocampal neuronal damage on acquisition and performance in the Morris water maze task was investigated in male Wistar rats, subjected to 8 min of transient forebrain ischemia, induced by the 4-vessel occlusion (4-VO) method. After a morphological scoring of the neuronal damage within the CA1, CA2, and CA3 subfields of the anterior-dorsal part of hippocampus we found that rats with a total neuronal cell loss of the anterior-dorsal CA1 region showed memory performance impairments in the acquisition trials, in a probe trial, and in a reversal experiment. However, rats with only partial damage to the CA1 region did not exhibit significant impairments during the acquisition trials of the water maze test or in the probe trial and the reversal experiment. In conclusion, these results suggest that it is possible to relate the histological damage score of CA1 in the anterior-dorsal hippocampus to impaired memory performance in the present water maze setup.

Animals↗