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PubMed1996

No evidence for involvement of angiotensin II in spatial learning in water maze in rats.

There is increasing evidence suggesting angiotensin II (AII) may inhibit memory formation in a range of conditioned avoidance and habituation learning tasks in rodents. We were interested to determine if AII might also play an inhibitory role in spatial learning. Angiotensin-converting enzyme (ACE) inhibitors, which block the formation of AII from AI, improve acquisition and/or retention of basal performance inhibited by the muscarinic receptor antagonist, scopolamine, in conditioned avoidance and habituation tasks. In hooded Wistar rats, over 5 days of training in a water maze neither the ACE inhibitor, ceranapril 5 and 50 micrograms/kg/day, nor the ACE inhibitor, ramipril 2 and 10 mg/kg/day, altered the increase in path length produced by administration of scopolamine 0.75 mg/kg/day. In probe trails (without platform), on the last day of training, ceranapril 50 micrograms/kg produced a 35% further deterioration in performance in the scopolamine-treated rats (P < 0.02). Administration of the substrate, renin, that leads to AII formation, did not alter water maze performance over 5 days of training. The angiotensin receptor antagonist, losartan, has been shown to improve basal and scopolamine-impaired performance in a habituation task and reverse the inhibition in long-term potentiation produced by diazepam. However, neither losartan 10 and 30 mg/kg/day nor ramipril 2 and 10 mg/kg/day reversed diazepam-impaired (3 mg/kg/day) acquisition of the spatial memory task over 5 days of training. These studies suggest AII does not inhibit spatial learning in rats in the constant platform position water maze task nor does it mediate the inhibitory effects of scopolamine or diazepam in this task.

Angiotensin II↗

PubMed1997

Evidence for recovery of spatial learning following entorhinal cortex lesions in mice.

The influence of entorhinal cortex lesions on behaviour and concommitant changes in synaptophysin immunoreactivity (IR) in the denervated dentate gyrus was assessed. Male, C57/B6 mice received either bilateral (BI), unilateral (UNI), or no lesion (SHAM) to the entorhinal cortex. At various stages post-lesion the animals were evaluated in tests to examine neurological and cognitive (spatial and cued learning, Morris water maze) function. UNI lesioned animals from 6-36 days post-lesion showed no neurological nor marked cued learning deficit, yet a profound spatial learning deficit. However by 70 days post-lesion, spatial learning ability was clearly evident. In contrast, BI lesioned animals showed severe spatial learning deficits throughout the test period (6-70 days), cued learning was also impaired. In parallel groups of UNI lesioned mice, 6-36 days post-lesion there was a marked reduction (-40%) in synaptophysin IR in the dentate gyrus molecular layer. However by 70 days post-lesion a clear increase in this measure was noted. Changes in the expression of the growth associated protein, GAP43, were also noted over this period. Taken together, the present results suggest some recovery of spatial learning following unilateral entorhinal cortex lesions in mice. This behavioural recovery of a hippocampally dependant task may be associated with a recovery of function related to the synaptic remodelling and elevation of synapse number in the denervated hippocampus, as evidenced by changes in synaptophysin and GAP43 IR.

Animals↗

PubMed1997

Testing hypotheses of spatial learning: the role of NMDA receptors and NMDA-mediated long-term potentiation.

The role of NMDA receptors and NMDA-mediated hippocampal long-term potentiation (LTP) in spatial learning was studied in rats using the competitive, systemically administered NMDA receptor antagonists CGS19755 ((+/-)-cis-4-phosphonomethyl-2-piperidine carboxylic acid) and NPC17742 (2R,4R,5S-2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid). CGS19755 caused sensorimotor disturbances and disrupted acquisition of the water maze in naive rats. The sensorimotor disturbances were greatly reduced and maze learning was normal in spite of the blockade of dentate gyrus LTP by CGS19755 in rats that had first been familiarized with the general task requirements by non-spatial pretraining. In a second experiment, antagonism of NMDA receptors caused small, but reliable, impairments in Y-maze and visible platform visual discrimination tasks. The results indicate that NMDA receptors are not crucial for water maze acquisition using a spatial learning strategy, and that NMDA antagonists cause visual and other sensorimotor disturbances in naive rats that could help account for their poor performance in this task.

Amino Acids↗

PubMed2005

A comparison of egocentric and allocentric age-dependent spatial learning in the beagle dog.

Spatial discriminations can be performed using either egocentric information based on body position or allocentric information based on the position of landmarks in the environment. Beagle dogs ranging from 2 to 16 years of age were tested for their ability to learn a novel egocentric spatial discrimination task that used two identical blocks paired in three possible spatial positions (i.e. left, center and right). Dogs were rewarded for responding to an object furthest to either their left or right side. Therefore, when the center location was used, it was correct on half of the trials and incorrect on the other half. Upon successful acquisition of the task, the reward contingencies were reversed, and the dogs were rewarded for responding to the opposite side. A subset of dogs was also tested on an allocentric spatial discrimination task, landmark discrimination. Egocentric spatial reversal learning and allocentric discrimination learning both showed a significant age-dependent decline, while initial egocentric learning appeared to be age-insensitive. Intra-subject correlation analyses revealed a significant relationship between egocentric reversal learning and allocentric learning. However, the correlation only accounted for a small proportion of the variance, suggesting that although there might be some common mechanism underlying acquisition of the two tasks, additional unique neural substrates were involved depending on whether allocentric or egocentric spatial information processing was required.

Aging↗

PubMed2002

Multigenerational exposure to dietary nonylphenol has no severe effects on spatial learning in female rats.

Nonylphenol is a common intermediate in the production of many consumer compounds and reportedly acts as an estrogen mimic. Because estrogen affects the spatial learning and memory in rats, the effects of nonylphenol exposure on the performance of female rats in the Morris water maze were investigated. Here, Sprague-Dawley rats (F0) consumed soy-free diets containing 0, 25, 200 or 750 ppm nonylphenol (0, 2, 16 or 60 mg/kg per day) beginning on postnatal day (PND) 42 and continuing for two generations (F1 and F2) with breeding occurring within treatments. Females to be behaviorally tested (n = 7-8 per treatment per generation) were ovariectomized at adulthood and assessed for spatial learning and memory between PND 125-150 (young adult age). Each rat was tested for four consecutive days (three trials per day) in the Morris water maze with the platform in a fixed location. One week later, each subject was primed with estrogen and progesterone and assessed on a single day (three trials). The F1 rats continued on the same diets until PND 380-395 (middle aged) when they were re-tested as above (four consecutive days followed 1 week later with hormonal priming and a single test day). Latency to find the platform, path length and swim speed were averaged over the three trials per day and analyzed using repeated measures analyses of variance. There were no consistent effects of dietary nonylphenol exposure and no interactions of nonylphenol exposure on any measure of performance in either generation at the young age nor at the middle age in the F1 generation. When tested at the young adult age, however, hormone priming resulted in latencies and path lengths that were significantly shorter than in those exhibited during the unprimed test days, and there was no such effect when tested at middle age. Middle aged rats exhibited better performance than the same animals tested at a young age, likely as a result of familiarity and practice with the test paradigm. These data suggest that multigenerational dietary nonylphenol exposure does not cause gross alterations in Morris water maze performance in young adult or middle aged ovariectomized female rats.

Animals↗

PubMed1990

Microinjection of dynorphin into the hippocampus impairs spatial learning in rats.

The effect of hippocampal dynorphin administration on learning and memory was examined in spatial and nonspatial tasks. Bilateral infusion of dynorphin A(1-8) (DYN; 10 or 20 micrograms in one microliters) into the dorsal hippocampus resulted in a dose-related impairment of spatial working memory in a radial maze win-stay task. Subsequent experiments found that acquisition of a reference memory task in the water maze was impaired by DYN injections (20 micrograms/microliters) in the dorsal hippocampus, but not in the ventral hippocampus, and that this impairment could be blocked by naloxone. In a nonspatial task, posttraining DYN injections in the dorsal hippocampus had no effect on retention of step-through passive avoidance. These results suggest that dynorphin specifically interferes with spatial learning and memory, and that this effect is mediated by opioid receptors in the dorsal hippocampus.

Animals↗

PubMed1992

Spatial learning impairment in a murine model of AIDS.

Mice infected with an immunosuppressive murine leukemia virus (MuLV) mixture, LP-BM5, displayed profound and selective deficits in spatial learning in a modified Morris water maze. These deficits appeared before the appearance of gross neurological impairment or histopathological changes in the central nervous system. Thus, LP-BM5-infected mice displayed deficits in several aspects of trained performance compared to controls. Furthermore, a failure to exhibit any evidence of task acquisition in this maze was observed almost twice as frequently (P less than 0.0005) in infected mice as in uninfected controls. Moreover, in the absence of gross visual, motoric, or motivational impairment, LP-BM5 MuLV-infected animals exhibited neither the target directed search pattern nor the spatial preference characteristic of controls. The spatial learning and memory deficit described here is the first report of cognitive impairment accompanying viral-induced immunosuppression in a nonprimate species.

Animals↗

PubMed2006

Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood.

Neurogenesis is known to take place in the adult brain. This work identifies T lymphocytes and microglia as being important to the maintenance of hippocampal neurogenesis and spatial learning abilities in adulthood. Hippocampal neurogenesis induced by an enriched environment was associated with the recruitment of T cells and the activation of microglia. In immune-deficient mice, hippocampal neurogenesis was markedly impaired and could not be enhanced by environmental enrichment, but was restored and boosted by T cells recognizing a specific CNS antigen. CNS-specific T cells were also found to be required for spatial learning and memory and for the expression of brain-derived neurotrophic factor in the dentate gyrus, implying that a common immune-associated mechanism underlies different aspects of hippocampal plasticity and cell renewal in the adult brain.

Animals↗

PubMedDate not supplied

Spatial learning in transgenic mice expressing human presenilin 1 (PS1) transgenes.

Dominant mutations in the Presenilin 1 gene are linked to an aggressive, early-onset form of familial Alzheimer's Disease (FAD). Spatial memory of transgenic (Tg) mice expressing either mutant (lines Tg(M146L)1, Tg(M146L)76, Tg(L286V)198) or wild type (line Tg(PS1wt)195) human PS1 transgenes was investigated in the Morris water maze (WM) test at 6 and 9 months of age. The results showed that the mutated Tg mice had increased swim speed when compared to non-Tg littermates or Tg PS1 wild type mice. The swim speed difference did not, however, significantly affect the spatial learning in the WM test and all groups showed comparable search paths during training and similar spatial bias during probe trials. When re-tested at 9 months, all mice showed significantly improved learning acquisition of spatial information. The lack of progressive spatial learning impairment in mice expressing the mutated human PS1 transgene in the WM does not preclude impairments in other cognitive tasks but suggests that full phenotypic expression of mutant PS1 alleles may require co-expression of human versions of other AD-associated genes.

Alzheimer Disease↗

PubMed2004

Retrosplenial cortex lesions of area Rgb (but not of area Rga) impair spatial learning and memory in the rat.

The retrosplenial cortex, which is situated in a critical position in the flow of information between the hippocampal formation and the neocortex, contributes to spatial memory, but no studies have examined the distinct contribution of each area of the retrosplenial cortex to this behavior. This study tests the hypothesis that the two areas of the retrosplenial granular cortex play distinct roles in spatial learning and memory. Adult, male Sprague-Dawley rats with small, bilateral lesions (ibotenic acid) of the retrosplenial granular cortex were tested for 2 weeks in a repeated acquisition water maze task. Compared to controls, rats with complete lesions of the retrosplenial granular b cortex (Rgb) were slightly, but significantly impaired, whereas rats with lesions of the retrosplenial granular a cortex (Rga) displayed no impairment. Further, the Rgb-lesioned (but not the Rga-lesioned) group was impaired in the probe trials at the end of the first week of training. All animals were tested in the same paradigm for a second week to determine if the learning and memory impairment in the Rgb-lesioned rats simply reflected "delayed learning." All animals improved their maze performance during the second week of testing, but the Rgb-lesioned group still had no preference for the correct quadrant in the probe trial. Together, these data indicate that Rgb plays a small, independent role in spatial learning and memory. Further, although selective lesions of Rga or Rgb do not cause a large deficit in learning, concomitant destruction of both areas causes a much greater impairment in learning than would be predicted from their independent contributions. The data highlight the unique and complex contribution of each area of the retrosplenial cortex to behavior.

Animals↗

PubMed2000

Low doses of 8-OH-DPAT prevent the impairment of spatial learning caused by intrahippocampal scopolamine through 5-HT(1A) receptors in the dorsal raphe.

1. We studied the effects of low doses of 8-OH-DPAT, a 5-HT(1A) receptor agonist, on the impairment of spatial learning caused by scopolamine injected into the CA1 region of the dorsal hippocampus of rats performing a two-platform spatial discrimination task. 2. Bilateral injections of 4 microg (in 1 microl) of scopolamine into the CA1 region of the dorsal hippocampus 10 min before each training session impaired choice accuracy with no effect on choice latency and errors of omission. 3. Administered subcutaneously 20 min before each training session, 8-OH-DPAT 10 and 30 (but not 3) microg kg(-1) did not modify choice accuracy but prevented the impairment by intrahippocampal scopolamine. 4. Injection of 1.0 microg (in 0.5 microl) of WAY 100635, a 5-HT(1A) receptor antagonist, into the dorsal raphe 5 min before scopolamine had no effect on choice accuracy and latency or errors of omission and did not modify the effect of scopolamine, but completely antagonized the effect of 10 and 30 microg kg(-1) 8-OH-DPAT on scopolamine-induced impairment of choice accuracy. 5. The results confirm previous findings that stimulation of presynaptic 5-HT(1A) receptors in the dorsal raphe attenuates the deficit of spatial learning caused by blockade of cholinergic excitatory input on hippocampal pyramidal cells. 6. Drugs that stimulate presynaptic 5-HT(1A) receptors such as 5-HT(1A) receptor partial agonists may be useful in the symptomatic treatment of human memory disturbances associated with loss of cholinergic innervation to the hippocampus.

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

PubMedDate not supplied

[Features of the c-Fos gene expression along the hippocampal rostro-caudal axis in common voles after rapid spatial learning].

The levels of the Fos protein expression in neurons was used as an index of transcription activation in the hippocampus of common voles (Microtus arvalis Pall.) after their rapid spatial learning. Fos-positive cells were stained and calculated in 20 brain sections along hippocampal rostro-caudal axis. Voles (learning group) were trained in a modified 8-arm radial maze to find the entry to the home cage through a target arm (6 trials per session, 2-hour session). The animals were pretrained to enter the home cage through an arm isolated from the maze. Animals of active control group continued entering the home cage through the isolated arm, and animals of the passive control group were taken for the Fos immunohistochemistry from the home cage. Both in the learning group and active control group, a significant increase in c-Fos expression was shown in all the examined areas (CA1, CA3 and the dentate gyrus) as compared to the passive control. A significant increase in the number of c-Fos positive neurons was observed in the caudal hippocampus of the learning animals as compared to the active control, however, no differences were found in the rostral part. The maximum effects were observed in the dentate gyrus and the CA3 field. The results suggest a functional rostro-caudal inhomogeneity of the vole's hippocampus in the spatial learning task.

Animals↗

PubMed2003

Impairments in spatial learning and memory: ethanol, allopregnanolone, and the hippocampus.

Acute ethanol administration impairs performance in many cognitive tasks that are dependent on hippocampal function. For example, acute ethanol administration produces dose-dependent impairments in spatial learning. Ethanol also decreases the spatial specificity of hippocampal place cells. Such findings raise the possibility that ethanol affects learning and memory by altering, either directly or indirectly, neuronal activity in the hippocampus and related structures. Acute ethanol administration induces a dose- and time-dependent increase in brain concentration of the neuroactive steroid allopregnanolone. Allopregnanolone is a potent GABAA receptor agonist and produces effects similar to the effects produced by ethanol. Blockade of de novo biosynthesis of allopregnanolone alters many of ethanol's effects including ethanol-induced suppression of spontaneous activity in medial septum/diagonal band of Broca neurons and hippocampal pyramidal neurons. These findings suggest that ethanol-induced increases in allopregnanolone levels might play a central role in the effects of acute ethanol on cognitive processing and hippocampal function. The impact of ethanol on spatial cognitive processing and hippocampal function will be reviewed. In addition, the possibility that ethanol-induced changes in neuroactive steroid levels contribute to the impact of ethanol on spatial learning and hippocampal function will be explored.

Animals↗

PubMed1987

Blockade of spatial learning by the M1 muscarinic antagonist pirenzepine.

Two experiments were conducted to determine the effects of the M1 muscarinic receptor antagonist pirenzepine on place navigation in a water maze. In the first experiment rats were required to learn the location of a hidden platform following intracerebroventricular injections of equimolar doses of pirenzepine or scopolamine methylbromide. Both drugs dose-dependently impaired spatial learning according to both escape latency data and transfer test analysis. Pirenzepine was approximately 3 times less potent than scopolamine, a potency ratio which suggests M1 receptor mediation of the impairment. In the second experiment pirenzepine (1 approximately 92.3 micrograms/rat ICV) was injected prior to training on a simultaneous place discrimination task in the water maze. Impairments of choice accuracy were found with a dose of 20 micrograms/rat in the absence of any marked increases in either errors of omission or choice latency. These data suggest that M1 receptor blockade impairs processes which are involved in spatial learning.

Animals↗

PubMed1992

Effects of haloperidol on the acquisition of a spatial learning task.

The effects of systemic injections of the dopaminergic antagonist haloperidol on the acquisition of the Morris water maze with either a visible or an invisible platform (nonspatial vs. spatial learning) were investigated. An open field test was used for selecting a dosage (< or = 0.1 mg/kg), that (hardly) affected locomotor behaviour. Differential effects were found. At 0.1 mg/kg, haloperidol reduced locomotion in the open field, impaired acquisition in the Morris maze with a visible platform, and blocked escape onto an invisible one. Even though 0.07 mg/kg haloperidol reduced locomotion, both 0.04 and 0.07 mg/kg only impaired Morris maze performance in the spatial version. A large effect was found in the first trial of every day's training block. These results indicate that haloperidol at low doses can lead to a moderate but significant impairment of spatial learning. It is suggested that the effects found are related to the function of the striatal areas in cue- and noncue-directed behaviour.

Animals↗

PubMed1993

Hippocampal choline acetyltransferase activity correlates with spatial learning in aged rats.

Age-related cognitive deficits in both humans and experimental animals appear to relate to dysfunction of basal forebrain cholinergic neuron systems. The present study assessed spatial learning performance in a water maze task as a function of choline acetyltransferase and high-affinity choline uptake specific activity (the two phenotypic markers for cholinergic neurons) in frontal cortex, hippocampus and striatum of aged male Fischer-344 rats. We observed that increased hippocampal choline acetyltransferase activity was related to better performance on the water maze task, and that, of the individual measures, hippocampal choline acetyltransferase activity was the best predictor of behavioral performance in the spatial learning task.

Aging↗

PubMed2006

Alterations in spatial learning and memory after forced exercise.

Exercise has been shown to influence learning and memory. Most studies were performed with a voluntary running paradigm (e.g. running wheel) in mice. However, such effects of exercise on learning and memory are less well demonstrated using a forced running paradigm (e.g. treadmill). The present study was designed to examine the effects of 12 weeks of forced treadmill running on learning and memory performance in rats. We have previously shown that forced running resulted in qualitative and quantitative changes in the cholinergic neurons of the horizontal diagonal band of Broca (HDB) in the septum. This study was conducted in order to determine whether or not these changes occur simultaneously with enhanced learning and memory. The one-day version of the Morris water maze (MWM) test [Frick, K.M., Stillner, E.T., Berger-Sweeney, J., 2000. Mice are not little rats: species differences in a one-day water maze task. NeuroReport 11, 3461-3465] was used to test spatial learning and memory after the exercise period. Our data showed that runners displayed better spatial learning and memory when compared to nonrunners. This was evidently shown by a reduction in the time required for spatial acquisition (p<0.05) and superior probe trial performance (p<0.05). A shorter distance swam by the runners also suggested improved learning over the nonrunners (p<0.05). In an attempt to revalidate our earlier quantitative results, we used design-based stereology (DBS) to estimate the number of cholinergic neuronal profile population in the medial septum and diagonal band (MSDB). We confirmed that forced running increased the cholinergic neuronal profile subpopulation in the HDB (Coefficient of Error<0.2). Taken together, these results indicate that forced exercise could influence learning and memory with a concomitant increase in the number of cholinergic neurons in the HDB.

Acetylcholinesterase↗

PubMed1996

Cellular correlates to spatial learning in the rat hippocampus.

Learning through exploration gives increased synaptic field potentials in the perforant path/dentate synapses, largely due to an activity-dependent brain temperature increase. After temperature compensation, spatial learning was associated with small, but significant, STP-like changes of the field potential lasting 20-30 min. A group of spatially trained adult rats showed faster spatial learning and about 10% higher basal dendritic spine density (LY-filled) compared to two control groups. With unchanged dendritic length and branching pattern, the results suggest the formation of new synapses.

Animals↗