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Preserved spatial memory in old rats survives 10 months without training.

Aged rats with extensive prior training on the radial maze retain the capacity for accurate spatial working memory (WM) for at least 3 months without practice. To investigate the temporal limits of this influence of prior experience we compared the reacquisition of spatial WM by a group of experienced 21.5-month-old rats to the original acquisition by naive 3-month-old rats. The aged rats had received 225 radial maze tests between 3 and 11 months of age. Despite 10 months without practice the old rats rapidly reacquired critical performance. Their reacquisition was markedly superior to original learning by the young rats, even when delays as long as 5 h were imposed between the rats' fourth and fifth choices during the daily tests in the eight-arm maze. Additional tests showed that neither young nor old rats employed a response strategy to maintain accurate spatial WM performance. Experience clearly confers long-lived protection against the otherwise deleterious effects of aging on spatial WM, but the mechanism by which this influence arises is unknown.

Aging↗

Massed but not spaced training impairs spatial memory.

The Morris water maze and the object displacement task are two popular tools used to investigate spatial learning and memory. Research has focused mainly on the acquisition of spatial tasks while little attention has been given to the retention phase. We examined the effects of different training procedures on retention of the water maze and also reactivity to spatial change in the object displacement task 7 days post-acquisition. We found that massed-trained animals were impaired on retention of the water maze compared to those animals that had received spaced-training. We also found that the massed-trained animals habituated readily to their environment in the object displacement task while the spaced-trained group did not. Furthermore the massed-trained group did not react to spatial change 7 days post-habituation compared to the increased reactivity displayed by the spaced-trained group. Results are discussed in terms of poor encoding of the environment leading to poor retention.

Analysis of Variance↗

Loss of NGF receptor immunoreactivity in basal forebrain neurons of aged rats: correlation with spatial memory impairment.

Nerve growth factor (NGF) has recently been implicated as a trophic agent in the survival and maintenance of basal forebrain cholinergic neurons. To test the hypothesis that NGF may play a role in the age-related decline of cerebral cholinergic function and loss of cognitive ability, we investigated the possible correlation between the loss of basal forebrain neurons that stain for NGF receptor, and impairment of spatial reference memory performance in aged rats. Our results suggest that NGF receptor-positive basal forebrain neurons undergo marked cell atrophy and loss of neuropil staining in aged rats exhibiting impaired spatial learning and memory performance. Conversely, numerous, densely immunoreactive perikarya and a profuse neuritic plexus within the basal forebrain nuclei was consistently observed in behaviorally intact rats. Overall, the mean number of NGF receptor-positive basal forebrain neurons both in the nucleus of the diagonal band and nucleus basalis correlated with retention of the spatial task (r = 0.84 and r = 0.67, respectively; P less than 0.01). Our results support the view that progressive failure of retrograde trophic support due to the age-related loss of NGF receptors may promote degenerative changes in basal forebrain cholinergic neurons, and contribute to deterioration of cognitive ability in senescence.

Aging↗

Effects of enriched postoperative housing conditions on spatial memory deficits in rats with selective lesions of either the hippocampus, subiculum or entorhinal cortex.

Long-Evans male, adult rats received selective and bilateral lesions of either the hippocampus, subiculum or lateral entorhinal cortex, and were then housed for 30 days in either enriched or standard conditions. Rats were then tested in the eight-arm radial maze to assess spatial working memory and the strategies that were employed (i.e. pattern of arms visited). Lesions of the hippocampus induced both a working-memory impairment and a loss in the use of allocentric strategies to perform the task. Rats with lesions of the subiculum were also impaired but less than hippocampectomized rats and showed a similar pattern of arm visits as control rats. In contrast with other lesioned rats, rats with lateral entorhinal cortex lesions performed the task like control rats. Postoperative enriched housing conditions (EHC) globally enhanced performance of rats, but did not affect the strategies selected by the rats to solve the task. The beneficial effect of EHC was particularly obvious in rats with lesions of the subiculum. In enriched rats with such lesions, performance was not significantly different from that of control rats housed in standard conditions. The present results indicate that 1) the structures within the hippocampal formation are not similarly involved in spatial learning and memory processes and in the management of navigational demands of the radial maze, and 2) enriched conditions may enhance the spared spatial abilities of some lesioned rats thus promoting functional recovery.

Journal Article↗

Anatomical specificity and time-dependence of chlordiazepoxide-induced spatial memory impairments.

Injection of the benzodiazepine (BDZ) chlordiazepoxide (CDP) into the medial septum (MS) produced a dose-dependent retrograde working memory deficit in a delayed non-match-to-sample radial-arm maze task. CDP (30 nmol; 10 micrograms) decreased the number of correct choices and increased the number of errors without altering latency to make arm choices. The effects of CDP were site specific; injection into regions proximate to the MS, including the lateral septum, the anterior cingulate, and the nucleus basalis magnocellularis, did not affect any index of performance. The second experiment demonstrated that CDP impaired working memory only when rats were injected either 0 or 60 min, but not 15, 30, or 45 min, following training. The MS appears (a) to contribute to both early (encoding/ maintenance) and late (retrieval/utilization) phases of working memory and (b) to be a critical site of action for BDZ-induced deficits in spatial working memory.

Animals↗

N-methyl-D-aspartate receptor antagonist MK-801 and spatial memory representation: working memory is impaired in an unfamiliar environment but not in a familiar environment.

Female Sprague-Dawley rats were injected with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 or saline 30 min before daily testing in spatial working memory (WM) and reference memory (RM) procedures in an 8-arm radial maze. MK-801 impaired RM and WM acquisition but not performance when rats were trained to criterion before drug administration. Neither a 2-hr nor a 4-hr delay between the first and last 2 correct WM choices impaired long-term WM. MK-801 impaired WM performance in trained rats only when rats were tested in a new environment. Thus, 2 mechanisms may be required for relational memory: an NMDA-dependent mechanism for acquiring long-term spatial representations and an NMDA-insensitive mechanism for operating on these stored representations.

Animals↗

A larger hippocampus is associated with longer-lasting spatial memory.

Volumetric studies in a range of animals (London taxi-drivers, polygynous male voles, nest-parasitic female cowbirds, and a number of food-storing birds) have shown that the size of the hippocampus, a brain region essential to learning and memory, is correlated with tasks involving an extra demand for spatial learning and memory. In this paper, we report the quantitative advantage that food storers gain from such an enlargement. Coal tits (Parus ater) a food-storing species, performed better than great tits (Parus major), a nonstoring species, on a task that assessed memory persistence but not on a task that assessed memory resolution or on one that tested memory capacity. These results show that the advantage to the food-storing species associated with an enlarged hippocampus is one of memory persistence.

Animals↗

Both here and there: simultaneous expression of autonomous spatial memories in rats.

Foraging rats learned to avoid footshock that was present in a part of a circular arena that was either stable or rotating slowly in a lighted room. The rotation dissociated spatial information in the separate reference frames of the room and arena. After learning to avoid the shocked region in either condition, in the absence of shock, memory for this place was expressed by simultaneous avoidance of an area defined in the reference frame of the room as well as of an area defined in the reference frame of the rotating arena. Spatial memories in these distinct reference frames were acquired, retrieved, and extinguished autonomously.

Animals↗

Spatial memory in alcohol-dependent subjects: using a push-button maze to test the principle of equiavailability.

The principle of equiavailability states that once the locations in a spatial array are learned, then all locations in the array are simultaneously available in memory (Levine, Jankovic, & Palij, 1982). To test the application of this principle, 21 nonamnesic, alcohol-dependent, male subjects and 20 demographic and ability-matched male control subjects were required to learn a series of push-button maze paths and to perform shortcut or retrace movements on the paths. The results for the control subjects conformed to the principle of equiavailability. In contrast, the alcohol-dependent subjects did not show equiavailability. This pattern of results is interpreted as evidence of a spatial memory deficit in the alcohol-dependent subjects.

Adult↗

Facilitative effects of an adenosine A1/A2 receptor blockade on spatial memory performance of rats: selective enhancement of reference memory retention during the light period.

The present experiment was designed to examine the role of adenosine in spatial working and reference memory in rats using an 8-arm radial maze task which requires the integrity of the hippocampal formation. We investigated the effects of the unselective adenosine A1/A2 receptor antagonist theophylline on acquisition and retention of spatial working and reference memory. As there is evidence that brain extracellular adenosine levels vary significantly during the light-dark cycle, we tested the effects of theophylline both during the light and the dark period. Acquisition of the task was investigated for 10 consecutive days after rats received daily injections of vehicle or theophylline (15 mg/kg, intraperitoneally). Retention was tested in two nondrug sessions 7 and 14 days after completion of acquisition. The results demonstrate that in saline-treated control rats acquisition and retention of reference memory and, to a lesser extent, working memory was superior in the dark period. The results further revealed that daily administration of theophylline interacted with days to selectively enhance reference memory acquisition in the light, but not in the dark, period. In addition, reference memory retention was significantly enhanced in those rats who learned the task under theophylline treatment during the light period. Overall, the results show that in saline-treated control rats the effectiveness of acquisition and retention of spatial information in a radial maze strongly depends on the time of day. The higher levels of maze performance in the dark period might be related to a better functioning of involved brain systems in the active period of the rat. Furthermore, theophylline-induced blockade of adenosine A1/A2 receptors in the light, but not in the dark, period selectively enhanced reference memory acquisition and retention. Variations of brain extracellular adenosine levels during the light-dark cycle might account for the restriction of reference memory enhancing effects of theophylline to the light period.

Animals↗

Consequences of Pentylenetetrazole Kindling on Spatial Memory and Emotional Responding in the Rat.

We investigated the consequences of pentylenetetrazole (PTZ) kindling on cognitive capacities of rats in a Morris water maze assessing spatial reference memory and in the spontaneous alternation test used as an index of working memory. The emotional consequences of PTZ kindling were also evaluated in an elevated plus maze test. Results indicated that PTZ kindled rats were not different from controls in mastering the water maze. However, PTZ kindled rats did not persist in searching the platform when evaluated at the end of learning. This suggests an altered place memory, although alternative explanations, like reduced anxiety, may be involved. Indeed, such anxiolytic activity was observed in a separate group of kindled rats evaluated in the plus maze test. No significant effect of PTZ kindling was noted in the spontaneous alternation test. These results question the generalization of previous results obtained in learning tests using electric shocks and illustrate the complexity of the PTZ model for the study of the behavioral consequences of kindling.

Journal Article↗

Effects of neonatal gonadal steroids on adult CA3 pyramidal neuron dendritic morphology and spatial memory in rats.

The hippocampus is implicated in spatial cognition, which is sexually dimorphic and developmentally sensitive to gonadal steroids. Previously we have shown a sex difference in CA3 pyramidal cell layer volume and neuronal soma size that was reversible with neonatal castration in males or prenatal treatment of females with either testosterone propionate (TP) or a nonaromatizable androgen, dihydrotestosterone propionate, but not estradiol benzoate, all of which correlated with adult water maze navigation. The present study further investigates developmental androgen sensitivity of CA3 pyramidal neurons by measuring dendritic morphology and its relation to adult spatial ability. Female rats were injected with TP on postnatal day (P) 3 and P5 or ovariectomized (OVX) on P2, and male rats were castrated on P2, with or without testosterone replacement (Cas+T). Sham surgery controls were also included. Animals were tested on a water maze in adulthood, sacrificed, and CA3 pyramidal neurons were Golgi-stained and reconstructed in three dimensions using a computer-interfaced morphometry system. High-androgen groups (control males, Cas+T, TP females) performed better in spatial navigation and exhibited CA3 neurons with longer dendrites, a larger number of dendritic branches, and volumes of influence compared to low-androgen groups (control females, castrated males, OVX). Collectively, these findings indicate that the critical time period for organizational effects of androgens on the CA3 pyramidal neurons includes both prenatal and postnatal life, during which time androgens regulate developmental events such as somal growth and neuronal differentiation, all of which significantly contribute to establishing the sex difference in adult spatial navigation.

Animals↗

Spatial memory and N-methyl-D-aspartate receptor antagonists APV and MK-801: memory impairments depend on familiarity with the environment, drug dose, and training duration.

Rats given N-methyl-D-aspartate (NMDA) antagonists were tested in the radial maze in spatial working memory (WM) and reference memory (RM) tasks. Female rats given (+)-10,11-dihydro-5-methyl-5H-dibenzo [a,d] cycloheptene-5,10 imine (MK-801; 0.0625 mg/kg ip) before daily testing in an 8-arm WM task were impaired even after 70 days. Control rats learned quickly, were assigned to a group given MK-801 or saline, and were trained to avoid 4 of the 8 arms. MK-801 impaired this reversal learning but did not affect WM performance. Male rats were trained on an 8-arm WM task for 19 days and then given intracranial aminophosphonovaleric acid (APV; 33 mM), which impaired both WM and motor behavior. Male rats were trained for 65 days to enter 4 of 8 arms and then given intracranial APV (20 or 30 mM). WM and RM were normal in the familiar environment but were both impaired in an unfamiliar environment. Results suggest that the mnemonic effects of NMDA antagonists depend on environmental familiarity, dose, and training duration.

2-Amino-5-phosphonovalerate↗

Behavioral parameters of the spatial memory correlate with the potentiation of the population spike, but not with the population excitatory postsynaptic potential, of the CA1 region in rat hippocampal slices.

Rats were tested for spatial performance in a water maze with further in vitro investigation of short-term and long-term potentiation (STP and LTP) in the CA1 region of the hippocampus. Recordings of the population spike in stratum pyramidale and population excitatory postsynaptic potential (EPSP) in stratum radiatum were made with extracellular electrodes after stimulation of the radiatum and oriens inputs in the region. It was found that for both inputs, STP and LTP of the population spike amplitude correlated with behavioral parameters of memory: latency of reaching the hidden platform (escape latency) and percent of time which the animal spent inside the quadrant with the platform. Potentiation of the initial slope of EPSP, in contrast, did not correlate with these parameters. These data support the hypothesis that hippocampal LTP may underlie spatial performance and show that potentiation of the output characteristic of the hippocampus (population spike), but not of the EPSP, is a physiological correlate for spatial memory.

Action Potentials↗

The retrieval of visuo-spatial memories by honeybees.

In order to explore how honeybees manage to retrieve the right landmark-memory in the right place, we trained bees along a short foraging route which consisted of two identical huts 33 m apart. Bees entered each hut to collect a drop of sucrose on the floor. The location of the drop was defined by the same arrangement of four blue and yellow cylindrical landmarks. However, in one hut the drop was between two yellow cylinders and in two other it was to the east of the blue cylinders. On tests with the sucrose missing, bees tended to search in the appropriate area in each hut (Fig. 1), thus showing that they used cues other than the sight of the local landmarks to select the appropriate memory. In a second experiment, the position of the sucrose was specified by yellow cylinders in one hut and by blue triangles in the other. When the arrays were swapped between huts, bees searched in the position specified by the array they encountered (Fig. 2). Thus, memories can be triggered by visual features of local landmarks. Bees were also trained outside to collect food from two platforms 40 m apart. The location of sucrose on one platform was defined by yellow cylinders, and on the other it was defined by blue triangles. When these arrays were exchanged between platforms, bees searched on each platform as though the landmarks had not been swapped. It seems that the more distant surroundings, which fill most of the visual field, may be more potent than the local landmarks in deciding which memory should be retrieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗