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A room with a view and a polarizing cue: individual differences in the stimulus control of place navigation and passive latent learning in the water maze.

We investigated individual differences in the stimulus control of navigational behavior in the water maze by comparing measures of place learning in one environment to measures of latent learning (via passive placement on the goal platform) in a novel environment. In the first experiment, 12 rats were trained to find a slightly submerged hidden platform at a fixed location in room A for 10 days (4 trials/day). Fast and slow place learners were identified by their mean escape latency and cumulative distance to the goal during acquisition. The same animals were then given a 2-min passive placement on the submerged platform in room B. Latent learning was assessed by the animal's escape latency on a single swim trial immediately following the placement in room B. The results showed that the good latent learners in room B were not necessarily the fast place learners in room A. This weak correlation may be related to the fact that some rats swam near the area in room B that corresponded to the former goal location in room A relative to a common polarizing cue (i.e., the door/entrance to both rooms). When the view of the door was blocked in a second experiment a significant positive correlation between place acquisition and the latent learning test was obtained, although escape performance following passive placement was not improved. These findings suggest that while place navigation and latent learning via passive placement may involve some common cognitive-spatial function, other associative (S-S and/or S-R) processes that occur during place navigation/active movement may be required for animals to exhibit truly accurate navigational behavior characteristic of asymptotic escape performance in the water maze. Additional implications for neurobiological studies using a procedural pretraining design are discussed.

Animals↗

The effect of nitric oxide synthase inhibition on cognitive ability and strategies employed for place learning in the water maze: sex differences.

Male and female rats use different cognitive strategies in the solution of place-learning problems in the water maze despite similar abilities. The female-type strategy has been negatively correlated with cortical nitric oxide (NO) metabolites. The present study aimed to examine the effect of NO synthase (NOS) inhibition (N(omega)-nitro-L-arginine, L-NA) on cognitive ability and strategy in the water maze, and to evaluate possible sex differences. In a 2 (male versus female) x2 (L-NA versus saline) factorial design, rats were trained to find the platform (visible or hidden), always in the same position, for 12 days. L-NA impaired acquisition, during the earlier phases and more prominently in females. This impairment was quite dramatic and unique to females during the first day that the platform was hidden following 3 days of visible-platform conditions. After acquisition, the visible platform's position was shifted, thereby presenting the rats with a choice (searching for the hidden platform in the previous location, i.e. adopting a conceptual cognitive style, or escaping to the visible platform in a new position, i.e. adopting a perceptual style). On the first of the four shift trials (where the newly positioned platform was proximal to the rat's starting position), female rats showed the previously found tendency to adopt a perceptual style escape directly in clear contrast to saline-treated males. The L-NA-treated males tended to manifest female-like perceptual style, suggesting that inhibition of NO synthesis in males weakened the tendency to choose a conceptual style in this shifted-platform task. The role of NO in both cognitive and non-cognitive psychological functions is discussed.

Animals↗

Prefrontal cortical mediation of rats' place learning in a modified water maze.

The acquisition of a place learning task in a water maze modified from the "standard" set-up by restriction of distal cues and addition of "proximal" cues (ping-pong balls in fixed positions on the surface of the water) was tested in three groups of rats: (I) animals subjected to bilateral ablation of the anteromedial prefrontal cortex, (II) rats in which the parietal "association" cortex had been removed bilaterally, and (III) a sham operated control group. The task acquisition of the prefrontally ablated group was significantly impaired, whereas the animals in which the parietal cortex had been removed acquired the task as quickly as the control group. Upon reaching criterion level performance all animals were tested on "challenge" sessions on which the cues were manipulated. Such "challenges" demonstrated that the animals of all three groups discriminated between the distal cues and utilized such a discrimination for navigational purposes.

Animals↗

An examination of the relations between hippocampal long-term potentiation, kindling, afterdischarge, and place learning in the water maze.

Two approaches were used to study the relations between the acquisition of place learning in the Morris water maze and long-term potentiation (LTP), kindling, and afterdischarge (AD). In the first, the possibility of behavioral LTP in the dentate gyrus field potential evoked by stimulation of the perforant path was evaluated in rats that showed robust place learning in the water maze. There was no effect of place learning on the field potential, and field potential measures did not correlate with place learning acquisition measures. In the second approach, the effect of bilateral saturation of LTP on subsequent place learning in the water maze task, begun within 5 minutes of the last LTP session, was evaluated. The effect of kindled seizures evoked bilaterally from the perforant path, or of a single unilateral AD, on acquisition of the water maze task (begun within 10 minutes) were also evaluated. Bilateral LTP saturation did not affect place learning, and the bilateral LTP group learned as readily as controls. In contrast, the kindled and AD groups were severely impaired in their performance of the place learning task. A second day of training in the water maze without any further electrical stimulation indicated that these groups had acquired considerable information on the first day of maze training and were not distinguishable from controls on the second day of training. This indicated that the deficit in these groups on the first day of training was temporary and likely resulted from a temporary perturbation of normal brain function due to the seizures. The results indicate that bilateral saturation of LTP in the dentate gyrus does not affect place learning in the water maze. They also indicate that recent hippocampal seizures, but not kindling, disrupt place learning in this task.

Animals↗

Partial reinforcement across trials impairs escape performance but spares place learning in the water maze.

We studied the effects of partial reinforcement on escape performance and place learning in the water maze. Rats given 50% reinforcement across trials (i.e. the escape platform was present only on odd trials) were compared to controls given 100% reinforcement (platform present on all trials). Control groups either received 8 or 4 trials per day, which was equal to either the total number of trials (100%-8) or reinforced escapes (100%-4) of the 50% group. Analysis of escape performance (latency) revealed that the 50% group was impaired relative to the 100%-8 group, but not the 100%-4 group, during the first 5 days of acquisition. The 50% group was impaired relative to both control groups on days 6-10 of overtraining. However, analyses of within-trial behavior (target annulus preference and thigmotaxis) on nonreinforced trials suggest that the 50% group did learn the location of the hidden platform (place information), in addition to a wall-based thigmotactic response. By dividing the 60s nonreinforced trials into three 20-s time bins, we were able to detect a significant preference for the target annulus early in the trial (bin 1 of trial 40 and bins 1-2 of trial 80). Further, there was a significant increase in time spent in the periphery of the pool, near the wall, in the last time bin of trial 40. Because the platform was in the middle zone, this behavior competed with a place response. We conclude that across-trial partial reinforcement procedures may promote response competition and mask evidence of place learning in addition to weakening escape performance late in training.

Animals↗

Time-place learning in the eight-arm radial maze.

Rats (n = 4) searched for food on an eight-arm radial maze. Daily 56-min sessions were divided into eight 7-min time zones, during each of which a different location provided food; locations were randomized across subjects before training. The rats obtained multiple pellets within each time zone by leaving and returning to the correct location. Evidence that the rats had knowledge about the temporal and spatial features of the task includes the following. The rats anticipated locations before they became active and anticipated the end of the currently active locations. The rats discriminated currently active locations from earlier and forthcoming active locations in the absence of food transition cues. After the rats had left the previously active location, they visited the next correct location more often than would be expected by chance in the absence of food transition cues. The rats used handling or opening doors as a cue to visit the first location and timed successive 7-min intervals to get to subsequent locations.

Animals↗

Reciprocal overshadowing between intra-maze and extra-maze cues.

In three experiments, rats learned a maze discrimination where the location of food was defined either by reference to extra-maze cues alone, or by both extra- and intra-maze cues. Experiment 1 confirmed earlier results in showing that the presence of intra-maze cues failed to overshadow learning about extra-maze cues, in spite of the former's apparently greater salience. Experiment 2, however, suggested that this result was an artefactual consequence of differences between groups in the proportion of reinforced and unreinforced trials during the course of discriminative training. In Experiment 3, the discrimination was taught by a series of reinforced and unreinforced placement trials, and a significant overshadowing effect was observed. Intra-maze and extra-maze cues seem to compete for association with reinforcement in exactly the same way as any other cues.

Animals↗

Clock mutant mice with Jcl/ICR background shows an impaired learning ability in water maze, but not in passive avoidance, at the beginning of dark phase.

We observed the learning ability in Clock mutant mice with Jcl/ICR background (Clockj), a mice model of evening-type individuals, in the early part of dark phase. In order to estimate the learning ability, Morris water maze (WM) and passive avoidance (PA) test were performed. Release of acetylcholine, 5 hydroxytryptophan (5-HT) and dopamine (DA) in hippocampus was measured by in vivo microdialysis method. Clockj showed the impaired learning ability in the WM, but not in PA test. Hippocampal acetylcholine release was significantly attenuated in the Clockj in comparison to the wild-type mice. Neither 5-HT nor DA in the hippocampus was affected by the Clock mutation. Clock, an essential gene controlling circadian rhythm, may have an important role on the spatial learning and hippocampal cholinergic function, at least, at the beginning of the dark phase.

5-Hydroxytryptophan↗

Spatial learning and memory, maze running strategies and cholinergic mechanisms in two inbred strains of mice.

The acquisition process of the radial maze task was studied in two inbred strains of mice, C57BL/6 and DBA/2. A quantitative and qualitative evaluation of performance was performed and the pretest level of activity was measured. The results showed a significant correlation between activity and performance since the highly active C57BL/6 mice exhibited better performance of the radial maze task than the less active DBA/2 mice. Moreover, for correct trials, strain-dependent maze-running strategies were observed: while both strains displayed about the same percentage of clockwise and spatial strategies, it was observed that among the spatial strategies C57BL/6 used a larger number of different correct solutions. Subsequently, the effect of scopolamine administration on working memory processes was assessed in sequential and discrete trials. A different reactivity of each strain to anti-cholinergic treatment was found in discrete trials since only DBA/2 mice were impaired. The effect of scopolamine is discussed in relation to the different models of information processing involved in learning and memorizing the experimental rule.

Animals↗

Contact with maternal parent and siblings affects hunting behavior, learning, and central nervous system development in spiderlings of Hogna carolinensis (Araeneae: Lycosidae).

The purpose of this study was to determine the effects of early experience (rearing conditions) on the central nervous system (CNS) and behavior of spiderlings of Hogna carolinensis (Lycosidae). We were interested in whether or not spiderlings that were allowed to remain in contact with their maternal parent and siblings (enriched condition, EC) would exhibit differences in CNS development or subsequent behavior when compared with those reared in isolation (improverished condition, IC). Spiderlings emerged from their egg sacs and climbed onto the dorsal surface of their mother's abdomen where they remained until their yolk supply was depleted (5 days). They dispersed on day 6 after emergence. We compared the ability of 16-day-old EC and IC spiderlings to capture prey in a linear runway and to learn a complex maze (spatial learning). We also compared certain aspects of CNS development (brain weight, total number of brain cells, volume of central body and protocerebral neuropil) in EC and IC spiderlings. Results indicated that EC subjects are more efficient at capturing moving prey (crickets) and exhibited improved performance (significantly fewer blind alley errors) in the maze. The volume of the protocerebral neuropil in 6-day-old EC animals increased 30% over a 5-day period after emergence as compared to IC animals of the same age. The volume of the central body of EC animals increased 34.8% over the same time period. On day 6 after emergence, the weight of the protocerebrum was significantly greater in EC versus IC subjects. There were no significant effects of rearing condition (EC vs IC) or age (1- and 6-day-old spiderlings) on the total number of nerve cells in the protocerebrum, suggesting that the difference in protocerebral weight was due primarily to differences in supporting glial tissues and neuropil matrix. In conclusion, the data suggest that early contact with the maternal parent and siblings is of vital importance to CNS development in lycosid spiderlings and can influence the capacity for spatial learning as well as the ability to capture prey.

Animals↗

Spermidine potentiates dizocilpine-induced impairment of learning performance by rats in a 14-unit T-maze.

The NMDA receptor, a ligand-gated ion channel complex, has been reported to be involved in memory processes. Learning is impaired following administration of dizocilpine, a non-competitive antagonist of the NMDA receptor. Polyamines, such as spermine and spermidine, interact with the NMDA receptor to enhance binding of dizocilpine, which blocks the ion channel. The present study assessed action of polyamines as modulators of learning via NMDA receptor activation. Dizocilpine (0.05 mg/kg) was given i.p. before maze learning, at a dose that produced a slight, nonsignificant impairment of maze learning. Pretreatment with 80 mg/kg but not 15 or 40 mg/kg spermidine (i.p.) before dizocilpine impaired maze learning compared to saline controls. Administration of 80 mg/kg spermidine without dizocilpine did not impair maze learning. The results are consistent with the view that systemic injection of a polyamine can modulate learning processes involving the NMDA receptor.

Analysis of Variance↗

Impaired spatial learning in aged rats is associated with loss of p75-positive neurons in the basal forebrain.

We investigated age-related changes in the number and size of neurons positive for the p75 neurotrophin receptor in the cholinergic basal forebrain of female Dark Agouti rats. Since the integrity of these neurons is known to be closely associated with performance in tests of spatial learning ability, we also investigated the incidence of age-related spatial learning impairments, using the Barnes maze. Spatial learning impairments occurred with increasing frequency with age. No rats showed impairment at six months, but 50% were impaired at 14 months and 71% at 26 months. There was no correlation between age and decreased number of p75-positive neurons in the rostral basal forebrain, which consists of the medial septum and vertical limb of the diagonal band of Broca. In the caudal basal forebrain, which consists of the horizontal limb and the nucleus of Meynert, there was a 13% reduction in the number of p75-positive neurons at 17 months compared to six months, and a 30% reduction at 26 months. There was a strong correlation between the presence of spatial learning impairment and a reduction in the number of p75-positive neurons. This correlation was most evident in the rostral basal forebrain, but was also present in the caudal basal forebrain. In the rostral basal forebrain, all learning impaired rats had fewer p75-positive neurons than the average number in unimpaired rats. A close correspondence between the presence of p75 and choline acetyltransferase was evident in basal forebrain neurons of learning-impaired and unimpaired rats. Gross pathological changes to the morphology of p75-positive neurons were relatively frequent in learning-impaired rats. These changes consisted of hypertrophy, appearance of vacuoles, and marginalisation of the cytoplasm. The results indicate the susceptibility of p75-positive neurons to degenerative changes with aging, and show that the loss of these neurons in the basal forebrain was strongly correlated with impairment in spatial learning.

Age Factors↗

An autoradiographic analysis of rat brain nicotinic receptor plasticity following dietary choline modification.

Choline is known to be involved with numerous physiological functions of the nervous system and also acts as a direct acting agonist of alpha7 nicotinic acetylcholine receptors (nAChRs). The purpose of this study was to conduct a brain region-specific evaluation of changes in nAChR subtype expression following dietary choline modification. In addition, we assessed changes in body weight, food/water intake, as well as changes in spatial learning (Morris Water Maze) in response to dietary choline modification. Male Sprague-Dawley rats were exposed to standard, choline supplemented or choline deficient diets for periods of 14 or 28 days. Choline supplemented animals gained significantly less weight over the course of the experiment, in spite of the fact that there were minimal differences in food consumption between the dietary regimens. Spatial memory did not differ between animals maintained on a standard rat diet, and the choline supplemented food. Brains of the animals kept on the diets for 14 and 28 days were used for quantitative autoradiographic analysis of nicotinic receptor subtypes using 125I-Bungarotoxin (alpha7) and 125I-Epibatidine (non-alpha7). There were no significant differences in nicotinic receptor binding or physiologic parameters measured between animals fed standard and choline deficient diets. However 2 weeks of dietary choline supplementation caused significant up-regulation of alpha7 receptors without significant effect on the density of non-alpha7 nAChRs. Increases in BTX binding predominantly occurred in cortical and hippocampal brain regions and ranged between 14 and 30% depending on the brain region. The results of our study suggest that choline acts as a selective agonist at alpha7 nicotinic cholinergic receptors in the rat central nervous system.

Animals↗

Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1-40) in rat.

Huperzine A, a promising therapeutic agent for Alzheimer's disease, was examined for its potential to antagonize the deleterious neurochemical, structural, and cognitive effects of infusing beta-amyloid protein-(1-40) into the cerebral ventricles of rats. Daily intraperitoneal administration of huperzine A for 12 consecutive days produced significant reversals of the beta-amyloid-induced deficit in learning a water maze task. This treatment also reduced the loss of choline acetyltransferase activity in cerebral cortex, and the neuronal degeneration induced by beta-amyloid protein-(1-40). In addition, huperzine A partly reversed the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax and P53 proteins and reduced the apoptosis that normally followed beta-amyloid injection. The present findings confirm that huperzine A can alleviate the cognitive dysfunction induced by intracerebroventricular infusion of beta-amyloid protein-(1-40) in rats. The beneficial effects are not confined to the cholinergic system, but also include favorable changes in the expression of apoptosis-related proteins and in the extent of apoptosis in widespread regions of the brain.

Alkaloids↗

Ethanol- and diazepam-induced cytochrome oxidase activity in mammillary bodies.

This study aims to analyze the effect of the administration of diazepam and alcohol on cytochrome c oxidase activity (COX) in the mammillary bodies (MB) with a quantitative densitometry method. The histochemical reaction of the COX is used as a reflection of energy consumption. Our results show an increase in the COX activity after treatment with diazepam in the different nuclei of MB: medial medial nucleus (MMNm), lateral medial nucleus (MMN1), and lateral nucleus (LMN) of the MB, the MMNm and LMN being significantly more active compared to the MMN1. Furthermore, the consequences of administering these drugs become manifest in spatial learning (water T maze). The performance in a spatial discrimination task did not prove to be impaired.

Animals↗