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PubMed1994

Effects of concomitant nicotinic and muscarinic blockade on spatial memory disturbance in rats are purely additive: evidence from the Morris water task.

This study reexamined the role played by a concurrent manipulation of nicotinic and muscarinic acetylcholine (ACh) receptors on performance of rats in the Morris water maze. A series of experiments was performed to test decreasing doses of scopolamine, a muscarinic ACh blocker, given concurrently with a fixed dose level of mecamylamine, a nicotinic ACh blocker, down to a subthreshold combination. Both substances were also tested separately. Data were analyzed to distinguish between a summative and a greater than additive (synergistic) effect of the two blocking agents. Our results fully support the important role played by ACh systems on cognitive functions and also show the substantial functional independence of the two ACh receptors in regulating spatial learning processes. In fact, data analysis did not reveal any significant interaction between the two ACh receptor blockers other than their additive effect: the hypothesis of a reciprocal modulation between the two ACh receptors, raised by some authors, cannot be supported for spatial learning mechanisms, at least with regard to the Morris water maze paradigm.

Animals↗
PubMed1983

Pigeons' spatial memory: III. Effect of distractors on delayed matching of key location.

The effect of distractors on pigeons' delayed matching of key location was investigated. Baseline trials began with a "ready" stimulus (brief operation of the grain feeder). Then one (randomly chosen) key from a three-by-three matrix was lit briefly as the sample. After a short delay (retention interval) the sample key was lit again along with one of the other eight keys. A peck at the key that had served as the sample (correct comparison) produced grain reinforcement, whereas a peck to the other key (incorrect comparison) produced only the intertrial interval. In Experiment 1, a houselight distractor, presented during either the sample, retention interval, or choice phases of the trial, had little if any effect on accuracy of matching key location. In Experiment 2, one of three types of spatial stimuli was interpolated during the retention interval, or the interval was blank as during baseline trials. The three stimuli were: the sample (correct comparison) location for that trial, the incorrect comparison location for that trial, or one of the seven unused locations for that trial. Relative to blank trials, accuracy improved slightly on sample-interpolated trials, decreased slightly on unused location-interpolated trials, and decreased considerably on incorrect comparison-interpolated trials. In Experiment 3, retention intervals were blank or had one of six types of interpolation: the sample, the incorrect comparison, two presentations of the sample, two presentations of the incorrect comparison, the sample followed by the incorrect comparison, or the incorrect comparison followed by the sample.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Intracellular correlates of spatial memory acquisition in hippocampal slices: long-term disinhibition of CA1 pyramidal cells.

Despite many advances in our understanding of synaptic models of memory such as long-term potentiation and depression, cellular mechanisms that correlate with and may underlie behavioral learning and memory have not yet been conclusively determined. We used multiple intracellular recordings to study learning-specific modifications of intrinsic membrane and synaptic responses of the CA1 pyramidal cells (PCs) in slices of the rat dorsal hippocampus prepared at different stages of the Morris water maze (WM) task acquisition. Schaffer collateral stimulation evoked complex postsynaptic potentials (PSP) consisting of the excitatory and inhibitory postsynaptic potentials (EPSP and IPSP, respectively). After rats had learned the WM task, our major learning-specific findings included reduction of the mean peak amplitude of the IPSPs, delays in the mean peak latencies of the EPSPs and IPSPs, and correlation of the depolarizing-shifted IPSP reversal potentials and reduced IPSP-evoked membrane conductance. In addition, detailed isochronal analyses revealed that amplitudes of both early and late IPSP phases were reduced in a subset of the CA1 PCs after WM training was completed. These reduced IPSPs were significantly correlated with decreased IPSP conductance and with depolarizing-shifted IPSP reversal potentials. Input-output relations and initial rising slopes of the EPSP phase did not indicate learning-related facilitation as compared with the swim and naïve controls. Another subset of WM-trained CA1 PCs had enhanced amplitudes of action potentials but no learning-specific synaptic changes. There were no WM training-specific modifications of other intrinsic membrane properties. These data suggest that long-term disinhibition in a subset of CA1 PCs may facilitate cell discharges that represent and record the spatial location of a hidden platform in a Morris WM.

Action Potentials↗
PubMed1995

A comparison of the effects of medial prefrontal, cingulate cortex, and cingulum bundle lesions on tests of spatial memory: evidence of a double dissociation between frontal and cingulum bundle contributions.

Rats were trained on an automated delayed nonmatching-to-position (DNMP) task. They then received cytotoxic lesions in either the medial prefrontal cortex (n = 13) or the cingulate and retrosplenial cortices (n = 8), or radiofrequency lesions in either the fornix (n = 6) or the cingulum bundle (n = 8). Twelve animals served as surgical controls. Only the fornical and medial prefrontal lesions disrupted DNMP performance, both groups showing a loss of accuracy and an increase in bias. The rats were then trained on a lever discrimination and reversal task, the medial prefrontal and fornical groups showing evidence of an increase in bias when compared with the cingulate cortex group. Finally, the rats were trained on a forced alternation task in a T-maze. Marked deficits were observed in the fornix and cingulum bundle groups, but the medial prefrontal and cingulate groups were unimpaired. The double dissociation between the effects of the prefrontal and cingulum bundle lesions highlights the very different nature of the two spatial tasks (DNMP and T-maze alternation), even though both involved a nonmatching rule. These findings may reflect the involvement of divergent outputs from the fornix-anterior thalamic pathway. One possibility is that anterior thalamic projections to the medial prefrontal cortex are concerned with processing egocentric information, while anterior thalamic projections to temporal regions via the cingulum bundle are concerned with allocentric information. The results also indicate that the effects of conventional lesions in the cingulate cortex and medial prefrontal cortex may be compromised by additional damage to the cingulum bundle.

Animals↗
PubMed1994

Memory for spatial layouts in relation to age and schema typicality.

The hypothesis that prior experience, specifically a knowledge-based schema for typical house layouts, can compensate for age declines in spatial memory was evaluated in 4 experiments. Old and young adults explored and subsequently recalled house layouts presented 1 room at a time on a computer screen. The findings failed to support the compensation hypothesis in that schema-relevant layouts facilitated recall equivalently for the 2 age groups. Violation of a typical house schema had a more negative effect on recall of the older group. Individual differences in spatial visualization ability explained much of the age difference in performance but not the effects of schema manipulations. It was concluded that there is age invariance in the facilitatory effects of relevant prior knowledge on spatial memory but an age-related decrease in the ability to inhibit irrelevant prior knowledge.

Adult↗
PubMed1992

Spatial memory in aged rats: population heterogeneity and effect of levocarnitine acetyl.

The existence in a population of aging rats of classes that display a different performance in the Morris water-maze test was investigated by cluster analysis procedure. These classes identified at 18 months of age showed a different response to levocarnitine acetyl and had a different behavioral profile when tested at 25 months of age. These findings demonstrate the need for an alternative interpretation of variability in animal populations as measured by the standard statistical analyses. The data analysis strategy we propose here will allow for the use of variability as a useful source of information.

Acetylcarnitine↗
PubMed1997

Symmetry and asymmetry of human spatial memory.

Six experiments investigated the limiting conditions on and the causes of asymmetries in estimates of euclidean distance. Participants estimated distances between locations on recently learned maps or between buildings on their college campus. Estimates between landmarks and neighboring nonlandmarks were often asymmetric, but estimates between other pairs of locations were typically symmetric. These and other results were inconsistent with the predictions of models that attribute asymmetries to stimulus or to retrieval bias. A contextual scaling model of asymmetry is proposed. According to this model, asymmetries in proximity judgments are caused by general principles of human memory and judgment: (a) Stimuli differ in the contexts they establish in working memory and (b) magnitude estimates are scaled by the context in which they are made.

Attention↗
PubMed1996

Bacterial alkaloids mitigate seizure-induced hippocampal damage and spatial memory deficits.

Studies of human patients with temporal lobe epilepsy and animal models of epilepsy have established relationships between seizures, excitotoxic hippocampal damage, and memory impairment. We report that bacterial alkaloids, recently shown to mimic actions of neurotrophic factors in cell culture, attenuate seizure-induced damage to hippocampal neurons and memory impairment in adult rats when administered subcutaneously. Intrahippocampal administration of convulsant doses of kainic acid (KA) to adult rats resulted in degeneration of neurons in CA3, CA1, and hilus. Rats administered KA exhibited (24 h later) deficits in performance on both goal latency and probe trial tasks in Morris water maze (MWM) tests of visuospatial memory. Seizure-induced damage to hippocampal neurons was significantly reduced, to varying extents, in rats administered the bacterial alkaloids K252a, K252b, or staurosporine (daily injections of 4 micrograms/kg body weight) prior to KA administration. The KA-induced deficits in MWM goal latency performance were abrogated in rats administered K252a or K252b, and K252a and staurosporine completely prevented seizure-induced impairment on the MWM probe trial. The alkaloids did not suppress electroencephalographic seizure activity, suggesting a dissociation between synchronization of activity and synaptically mediated excitotoxic injury to hippocampal neurons. Each alkaloid caused an increase in levels of protein tyrosine phosphorylation as determined by Western blot analysis of hippocampal tissue. Our data indicate that these bacterial alkaloids have potent antiexcitotoxic activities which may have clinical utility in epilepsy and other disorders that involve excitotoxic damage.

Alkaloids↗
PubMed2000

HIV- and FIV-derived gp120 alter spatial memory, LTP, and sleep in rats.

Human immunodeficiency virus (HIV)-associated dementia (HAD) has been detected in 20-30% of patients suffering AIDS. The envelope glycoprotein 120 (gp120) derived from HIV seems to play a critical role in the pathophysiology of this dementia. Likewise, the feline immunodeficiency virus (FIV)-derived gp120 causes neurological and electrophysiological abnormalitites in cats. We have studied the effects of gp120 derived from HIV or FIV on learning and memory processing, hippocampal long-term potentiation (LTP), hippocampal neuronal cAMP production, the sleep-waking cycle, and locomotor activity and equilibrium in rats. Results showed that while both HIV- and FIV-gp120 impaired the rat's performance in the Barnes maze task, only HIVgp120 impaired the induction and maintenance of LTP. However, both glycoproteins induced a significant decrease in the posttetanic potentiation. HIVgp120 also caused a significant reduction in cAMP production in the hippocampus. Regarding the sleep-waking cycle, HIV- and FIV-gp120 increased the waking state and slow-wave sleep 1 (SWS1), while decreasing both SWS2 and REM sleep. Locomotor activity and equilibrium were significantly altered by these glycoproteins. These results suggest that HIVgp120 causes neurophysiological abnormalities and therefore may facilitate HAD development in AIDS patients.

AIDS Dementia Complex↗
PubMed1986

Landmark learning and visuo-spatial memories in gerbils.

The aim of this study is to understand what a rodent (Meriones unguiculatus) learns about the geometrical relations between a goal and nearby visual landmarks and how it uses this information to reach a goal. Gerbils were trained to find sunflower seeds on the floor of a light-tight, black painted room illuminated by a single light bulb hung from the ceiling. The position of the seed on the floor was specified by an array of one or more landmarks. Once training was complete, we recorded where the gerbils searched when landmarks were present but the seed was absent. In such tests, gerbils were confronted either with the array of landmarks to which they were accustomed or with a transformation of this array. Animals searched in the appropriate spot when trained to find seeds placed in a constant direction and at a constant distance from a single cylindrical landmark. Since gerbils look in one spot and not in a circle centred on the landmark, the direction between landmark and goal must be supplied by cues external to the landmark array. Distance, on the other hand, must be measured with respect to the landmark. Tests in which the size of the landmark was altered from that used in training suggest that distance is not learned solely in terms of the apparent size of the landmark as seen from the goal. Gerbils can still reach a goal defined by an array of landmarks when the room light is extinguished during their approach. This ability implies that they have already planned a trajectory to the goal before the room is darkened. In order to compute such a trajectory, their internal representation of landmarks and goal needs to contain information about the distances and bearings between landmarks and goal. For planning trajectories, each landmark of an array can be used separately from the others. Gerbils trained to a goal specified by an array of several landmarks were tested with one or more of the landmarks removed or with the array expanded. They then searched as though they had computed an independent trajectory for each landmark. For instance, gerbils trained with an array of two landmarks were tested with the distance between two landmarks doubled. The animals then searched for seeds in two positions, which were at the correct distance and in the right direction from each landmark.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Early post-natal administration of 5,7-dihydroxytryptamine destroys 5-HT neurons but does not affect spatial memory.

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) may play an important role in learning and memory. It has also been suggested that 5-HT abnormalities may mediate some aspects of the cognitive disorders associated with Korsakoff syndrome and Alzheimer's Disease. The effect of intracisternally applied 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) on learning and memory in rodents was evaluated. Three-day-old rat pups were treated with pargyline (40 mg/kg, i.p.) followed by 5,7-DHT (50 micrograms/pup) and returned to the dam for a month. At 75 days of age, rats were tested on a learning set problem in the Morris water maze for 5 days followed by 30 days of testing in a 12-arm radial maze with 8 of the 12 arms baited. In the Morris water maze, the latency to locate the hidden platform did not differ significantly for 5,7-DHT treated and control rats (F less than 1.0). Similarly, 5,7-DHT treated rats performed comparably to controls on the 12-arm radial maze (F less than 1.0). At 106 days of age the assay of tryptophan hydroxylase activity in the dorsal raphe nuclei and hippocampus showed marked reduction (86%, 78%, respectively) in 5,7-DHT treated animals compared to vehicle injected controls. Immunocytochemical analysis was consistent with the biochemical results. In 5,7-DHT treated animals there was severe loss of neurons that bind 5-HT antibody in the dorsal and medial raphe nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗