Visible Platform Task Research Articles

Post-training cyclooxygenase-2 (COX-2) inhibition impairs memory consolidation.

Evidence indicates that prostanoids, such as prostaglandins, play a regulatory role in several forms of neural plasticity, including long-term potentiation, a cellular model for certain forms of learning and memory. In these experiments, the significance of the COX isoforms cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in post-training memory processes was assessed. Adult male Long-Evans rats underwent an eight-trial (30-sec intertrial interval) training session on a hippocampus-dependent (hidden platform) or dorsal striatal-dependent (visible platform) tasks in a water maze. After the completion of training, rats received an intraperitoneal injection of the nonselective COX inhibitor indomethacin, the COX-1-specific inhibitor piroxicam, the COX-2-specific inhibitor N-[2-cyclohexyloxy-4-nitrophenyl]-methanesulfonamide (NS-398), vehicle (45% 2-hydroxypropyl-beta-cyclodextrin in distilled water), or saline. On a two-trial retention test session 24 h later, latency to mount the escape platform was used as a measure of memory. In the hidden platform task, the retention test escape latencies of rats administered indomethacin (5 and 10 mg/kg) or NS-398 (2 and 5 mg/kg) were significantly higher than those of vehicle-treated rats, indicating an impairment in retention. Injections of indomethacin or NS-398 that were delayed 2 h post-training had no effect on retention. Post-training indomethacin or NS-398 had no influence on retention of the visible platform version of the water maze at any of the doses administered. Furthermore, selective inhibition of COX-1 via post-training piroxicam administration had no effect on retention of either task. These findings indicate that COX-2 is a required biochemical component mediating the consolidation of hippocampal-dependent memory.

Behavioral tests of hippocampal function: simple paradigms complex problems

Behavioral tests have become important tools for the analysis of functional effects of induced mutations in transgenic mice. However, depending on the type of mutation and several experimental parameters, false positive or negative findings may be obtained. Given the fact that molecular neurobiologists now make increasing use of behavioral paradigms in their research, it is imperative to revisit such problems. In this review three tests, T-maze spontaneous alternation task (T-CAT), Context dependent fear conditioning (CDFC), and Morris water maze (MWM) sensitive to hippocampal function, serve as illustrative examples for the potential problems. Spontaneous alternation tests are sometimes flawed because the handling procedure makes the test dependent on fear rather than exploratory behavior leading to altered alternation rates independent of hippocampal function. CDFC can provide misleading results because the context test, assumed to be a configural task dependent on the hippocampus, may have a significant elemental, i.e. cued, component. MWM may pose problems if its visible platform task is disproportionately easier for the subjects to solve than the hidden platform task, if the order of administration of visible and hidden platform tasks is not counterbalanced, or if inappropriate parameters are measured. Without attempting to be exhaustive, this review discusses such experimental problems and gives examples on how to avoid them.

Differential Interaction of Platelet-Activating Factor and NMDA Receptor Function in Hippocampal and Dorsal Striatal Memory Processes

The interaction between platelet activating factor (PAF) and NMDA receptor function in hippocampal and dorsal striatal memory processes was examined. In both a hidden and a visible platform water maze task, peripheral post-training injection of MK-801 (0.05 mg/kg) impaired memory. Post-training intrahippocampal infusions of PAF (1.0 μg/0.5 μl) enhanced memory in the hidden platform task, while intradorsal striatal infusion of PAF (1.0 μg/0.5 μl) enhanced memory in the visible platform task. The memory impairing effects of post-training injection of MK-801 was blocked by concurrent intrahippocampal infusion of PAF. In contrast, post-training injection of MK-801 blocked the memory enhancing effects of concurrent intradorsal striatal infusion of PAF. The results suggest that (1) the memory enhancing effects of intracerebral PAF infusion involve an interaction with NMDA receptor function, and (2) the nature of this interaction may represent a differential mechanism mediating the distinct roles of the hippocampus and dorsal striatum in cognitive memory and stimulus-response habit formation, respectively.

A single high dose of dizocilpine produces long-lasting impairment of the water maze performance in adult rats

The long-lasting effects of a single high dose treatment with the non-competitive N-methyl- d-aspartate (NMDA) antagonist dizocilpine (MK-801; 10 mg/kg, i.p.) on the water maze performance of rats were investigated. MK-801-treated rats learned to find the escape platform at a slower rate than control animals, and showed increased thigmotaxis during acquisition of the task. However, no differences were found between MK-801 and control groups on the probe trial, during repeated acquisition and on the visible platform task. These findings further support the idea that NMDA antagonists can be used in animal research to model persisting symptomatology of cognitive and psychotic disorders.

Synaptic reorganization in the hippocampal formation of alcohol-fed rats may compensate for functional deficits related to neuronal loss

We have examined the behavioral and neuroanatomical effects of long-term alcohol intake in rats ingesting a 20% solution of ethanol for 30 weeks. Previous studies have shown that this treatment provokes neuronal degeneration in the hippocampal formation, which occurs in parallel with remodeling processes. Spatial reference and working memory of alcohol-fed rats were evaluated during last 4 weeks of treatment by comparison of their performance with age-matched controls on the Morris water maze. Alcohol consumption did not affect the performance of rats in the reference memory task as indicated by the measures derived from the acquisition trials and from the probe-trial, which were highly similar for alcohol-fed and control animals. Also, performance in the working memory task was not significantly altered in alcohol-treated animals. No treatment-related changes in swim speed or impairments of sensorimotor abilities, tested in the visible platform task, were detected. Stereological methods were applied to evaluate the damage inflicted by alcohol intake in the structure of the hippocampal formation. In the alcohol-treated animals, there was a noticeable cell loss in the granular layer of the dentate gyrus (10%), and in CA3 (18%) and CA1 (19%) hippocampal subdivisions. In spite of the neuronal loss, the total number of synapses between mossy fibers and CA3 pyramids was unaffected by alcohol treatment suggesting that new synaptic contacts were formed between the surviving neurons. We show that, regardless the marked hippocampal cell loss in rats exposed to chronic alcohol intake, the reorganization that takes place at the synaptic level may alleviate the expected functional deficits.

Impaired water-maze performance in mice lacking transcription factor CCAAT/enhancer-binding protein ?

To gain a clue to whether the transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) is implicated in mouse behavior, the water maze performance of C/EBPβ(-/-) mice was compared with the performance of their wild type (WT) controls. The escape latencies of C/EBPβ(-/-) mice increased along with the number of trials within all training sessions in the hidden-platform tasks. Even in the visible-platform tasks, their escape latencies did not decrease along with the number of trials. The unusual performance in C/EBPβ(-/-) mice during later trials may allow us to presume that they suffer certain emotional vulnerability to stress from the water-maze training, although the involvement of other factors such as motor or immune system should be also considered.

A Necessity for MAP Kinase Activation in Mammalian Spatial Learning

Although the biochemical mechanisms underlying learning and memory have not yet been fully elucidated, mounting evidence suggests that activation of protein kinases and phosphorylation of their downstream effectors plays a major role. Recent findings in our laboratory have shown a requirement for the mitogen-activated protein kinase (MAPK) cascade in hippocampal synaptic plasticity. Therefore, we used an inhibitor of MAPK activation, SL327, to test the role of the MAPK cascade in hippocampus-dependent learning in mice. SL327, which crosses the blood-brain barrier, was administered intraperitoneally at several concentrations to animals prior to cue and contextual fear conditioning. Administration of SL327 completely blocked contextual fear conditioning and significantly attenuated cue learning when measured 24 hr after training. To determine whether MAPK activation is required for spatial learning, we administered SL327 to mice prior to training in the Morris water maze. Animals treated with SL327 exhibited significant attenuation of water maze learning; they took significantly longer to find a hidden platform compared with vehicle-treated controls and also failed to use a selective search strategy during subsequent probe trials in which the platform was removed. These impairments cannot be attributed to nonspecific effects of the drug during the training phase; no deficit was seen in the visible platform task, and injection of SL327 following training produced no effect on the performance of these mice in the hidden platform task. These findings indicate that the MAPK cascade is required for spatial and contextual learning in mice.

Rat strain differences in response to galanin on the Morris water task

Galanin acts as an inhibitory modulator of cholinergic transmission in the septohippocampal pathway of the rat. Centrally administered galanin induces performance deficits on rodent learning and memory tasks, including delayed non-matching to position, T-maze delayed alternation, passive avoidance, starbust radial maze acquisition, and the Morris water task. The present study investigates differences in responsiveness to intraventricularly administered galanin across three strains of laboratory rat on acquisition of spatial learning in the Morris water task. Sprague–Dawley rats showed normal performance during training, but lack of selective quadrant search on the probe trial in response to galanin treatment. Long–Evans rats showed no effects of galanin on performance during training or probe trial. Wistar rats showed longer latencies to reach the hidden platform during training, and lack of selective quadrant search on the probe trial in response to galanin. Performance on the visible platform task and on locomotor activity in the open field was normal in rats treated with galanin. These results are consistent with an interpretation of strain differences in sensitivity to the inhibitory actions of galanin on learning and memory.

Dissociation of multiple memory systems by posttraining intracerebral injections of glutamate

The role of glutamatergic transmission in the memory functions of the hippocampus and the caudate-putamen was examined using posttraining intracerebral injections of glutamate. Rats received an eight-trial (30-sec intertriai interval) training session on a hidden or visible platform task in a water maze. In the hidden platform task, a submerged escape platform was located in the same quadrant of the maze on all trials. In the visible platform task, a visible escape platform was located in a different quadrant of the maze on each trial. Following Trial 8 in either task, rats received a posttraining intrahippocampal or intracaudate injection of glutamate or saline. On a two-trial retention test session 24 h later, latency to mount the escape platform was used as a measure of memory. In the hidden platform task, the retention test escape latencies of rats receiving intrahippocampal injection of glutamate (2 µg) were significantly lower than those of vehicle-treated rats, indicating an enhancement of memory. Intracaudate injection (2, 5, or 10 µg) of glutamate had no effect on memory in the hidden platform task. In contrast, intracaudate injection of glutamate (5 µg) enhanced memory in the visible platform task, whereas intrahippocampal injection (1, 2, or 5 µg) had no effect. In both tasks and brain structures, intracerebral injections of glutamate had no effect on memory when delayed 2 h posttraining, indicating a time-dependent effect of glutamate on memory storage processes. The findings indicate a double dissociation of the roles of the hippocampus and the caudate-putamen in memory and suggest that glutamate modulates the distinct forms of memory mediated by these two brain structures.

Neonatal binge ethanol exposure using intubation: timing and dose effects on place learning.

Neonatal rats were given ethanol using an acute intubation procedure that resulted in daily binge-like exposure with minimal effects on somatic growth. Acquisition of place learning in the Morris water maze was evaluated on postnatal days (PD) 26-31. In Experiment 1, a total of 5.25 g/kg/day of ethanol was administered in two daily intubations on PD 4-6, PD 7-9, or PD 4-9, producing mean peak BACs of 265 mg/dL. Place learning acquisition deficits in a 114-cm-diameter tank were found for the PD 4-9 and PD 7-9 groups, but not the PD 4-6 group. In Experiment 2, either 4.5 or 5.25 g/kg/day of ethanol was administered on PD 7-9 and place learning was tested in a 171-cm-diameter tank. Significant acquisition deficits resulted from the higher dose, and probe trial search patterns for both ethanol groups were significantly less localized than controls. In Experiment 3, no significant effects of either PD 7-9 dose were found on a visible platform task. These findings reveal selective place learning deficits in this intubation model of neonatal binge exposure, and confirm a temporal window of vulnerability to spatial learning deficits during the second neonatal week.

Memory and the effect of cold shock in the water maze in S100β transgenic mice

S100β, a calcium binding astrocytic brain protein, influences hippocampal long-term potentiation (LTP) and depression (LTD), synaptic processes suggested to play role in spatial (contextual) learning and memory. In the present study we trained S100β transgenic and wild-type control mice in a nonspatial version of the Morris water maze, the visible platform task, and analyzed retention of memory over periods of 18 h, several days, and weeks. The results show that acquisition and retention were not altered in the S100β transgenic mice compared to control. However, a single alteration of an environmental stimulus, water temperature, significantly worsened the performance of transgenic mice. This impairment lasted for two consecutive trials separated by a 2-week intertrial interval, suggesting a temporary disturbance associated with memory processes. We discuss the possibility that these results are compatible with normal cortical but abnormal hippocampal functioning in the S100β transgenic mice.

Effect of aging on the spatial learning deficit produced by diazepam in rats

1. 1. After pretraining in an undrugged state, young (6 months) and aged (18–24 months) rats were trained on a spatial learning-set task after receiving one of four doses of diazepam (1, 2, 3 or 5 mg/kg) or the drug vehicle. The effects of 5 mg/kg of diazepam were also assessed on the spatial learning-set task one full hour after injection (delay condition) as well as on the visible platform task. 2. 2. During pretraining (undrugged), aged rats demonstrated a transient impairment on the visible platform task but subsequently did not differ significantly from young rats on the submerged platform task. On the spatial learning-set task, aged rats performed as well as young rats under control conditions and diazepam produced a comparable dose-dependent impairment of spatial learning. However, when the 1 hr delay was interposed between diazepam administration and maze testing, only aged rats exhibited a spatial learning impairment. Diazepam did not impair performance on the visible platform task in either young or aged rats. 3. 3. These results indicate that although the amnesic effect of diazepam is not initially greater in aged rats, it persists for longer periods.

Baclofen, a selective GABA B receptor agonist, dose-dependently impairs spatial learning in rats

The present investigation assessed the effects of the selective GABA B receptor agonist baclofen (1, 3, and 6 mg/kg) on spatial learning in the Morris water maze, an aversively motivated spatial learning task. Potential anxiolytic and sedative effects of baclofen were also assessed in an open field. Baclofen dose-dependently reduced locomotion in the open field but had little effect on thigmotaxia (anxiety). In the water maze, baclofen dose-dependently impaired spatial learning and reduced swim speed. During the probe trial given after training, only rats treated with the highest dose of baclofen (6 mg/kg) failed to show a bias for the correct quadrant. Following four additional retraining trials, a second drug-reversal probe trial was given and it was found that rats switched from saline to the highest dose of baclofen (6 mg/kg) showed a bias for the correct quadrant, as did rats switched from the two lowest doses of baclofen (1 and 3 mg/kg) to saline. Rats switched from the highest dose of baclofen (6 mg/kg) to saline failed to show a quadrant bias. Performance on a visible platform task was not impaired by baclofen at any dose. Together these results suggest that baclofen resembles GABA A agonists/positive modulators in that it impairs spatial learning, but not performance of a previously acquired escape response, but differs in that it does not reduce thigmotaxia (anxiety). Potential mechanisms by which baclofen impairs mnemonic processes are discussed.