Water Maze Spatial Memory Task Research Articles

Forgetting and receptor removal

Neuroscience The trafficking of AMPA receptors to and from the surface of postsynaptic membranes regulates synaptic strength and underlies learning and memory. Awasthi et al. found that the integral membrane protein synaptotagmin-3 (Syt3) is predominantly found on postsynaptic endocytic zones of neurons, where it promotes AMPA receptor internalization (see the Perspective by Mandelberg and Tsien). In Syt3 overexpressing or knockdown neurons, synaptic transmission and short-term plasticity were unchanged. However, in neurons from Syt3 knockout mice, synaptic long-term depression was abolished and decaying long-term potentiation endured. In Syt3 knockout mice, spatial learning was unaltered; however, these animals showed signs of impaired forgetting and relearning during the water maze spatial memory task. Science , this issue p. [eaav1483][1]; see also p. [31][2] [1]: /lookup/doi/10.1126/science.aav1483 [2]: /lookup/doi/10.1126/science.aaw1675

Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting.

Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that synaptotagmin-3 (Syt3) localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA receptor internalization, long-term depression (LTD), and decay of long-term potentiation (LTP) of synaptic strength required calcium-sensing by Syt3 and were abolished through Syt3 knockout. In spatial memory tasks, mice in which Syt3 was knocked out learned normally but exhibited a lack of forgetting. Disrupting Syt3:GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting, and these effects were occluded in the Syt3 knockout background. Our findings provide evidence for a molecular mechanism in which Syt3 internalizes AMPA receptors to depress synaptic strength and promote forgetting.

Preventive and therapeutic effects of environmental enrichment in Wistar rats submitted to neonatal hypoxia-ischemia

Environmental enrichment (EE) at early stages of neurodevelopment attenuates HI-induced behavioral, histological and cellular damage. However, the effects of EE exposure during gestational or early postnatal period and the possible influence of sexual dimorphism on EE protection are not fully understood. Present study evaluated the effects of pre-natal and postnatal EE, as well as their combination, in male and female rats submitted to neonatal HI at postnatal day (PND) 3. Wistar rats were housed in EE or in standard condition (SC) during all pregnancy. At PND1, the litters were randomly allocated to the same prenatal environment during lactation (SC + SC or EE + EE) or housed in a new environment until weaning (SC + EE or EE + SC). Behavioral tasks were performed from PND 60-75. Then, animals were euthanized for biochemical and histological analysis. Prenatal and early postnatal EE alone improved performance of HI males in the Water Maze spatial memory task, while HI females were most benefited from early postnatal stimulation. Moreover, EE attenuated HI-induced lower anxiety-like behavior in rats of both sexes and decreased hyperlocomotion in HI females. Hippocampus tissue preservation and higher VEGF and TrkB levels were observed in all HI groups exposed to EE. Interestingly, HI males exposed to prenatal or postnatal EE alone exhibited higher GFAP levels and additional tissue preservation. Therefore, both prenatal and early postnatal environmental enrichment cause attenuation of HI-induced impairments, revealing their preventive and therapeutic actions, possibly due to VEGF and astrocyte activity; some of these effects are sex-specific.

Brain Interleukin-1 Facilitates Learning of a Water Maze Spatial Memory Task in Young Mice

The proinflammatory cytokine interleukin-1 (IL-1) is produced by many types of cells, including immune cells in the periphery and glia and neurons in the brain. The type I IL-1 receptor (IL-1r1) is primarily responsible for transmitting the inflammatory effects of IL-1 and mediates several biological functions by binding to either IL-1α or IL-1β. IL-1β activation is associated with hippocampus-dependent memory tasks. Although IL-1β impairs spatial memory under certain pathophysiological conditions, IL-1β may be required for the normal physiological regulation of hippocampal plasticity and memory. In addition, brain IL-1β levels are thought to change in the hippocampus in an age-dependent manner. These findings suggest that IL-1β may have a beneficial, temporary effect on learning and memory in young mice, but the matter remains unclear. Therefore, we hypothesized that hippocampal IL-1β has a beneficial effect on spatial learning and memory in young mice via IL-1r1, which is diminished in adults. We investigated the performance of young (3-month-old) and adult (6-month-old) wild-type mice, IL-1β knockout mice (IL-1βko) and IL-1r1 knockout mice (IL-1r1ko) in learning a spatial memory task with a fixed platform in a water maze (WM) and measured the levels of IL-1β and IL-1α in the hippocampus and cortex of adult and young mice by using homogeneous time-resolved fluorescence (HTRF). Learning was significantly impaired in the training trials of the WM spatial memory task in young IL-1βko and IL-1r1ko mice but not in adult IL-1βko and IL-1r1ko mice. Moreover, young IL-1r1ko mice but not IL-1βko mice showed an impairment in long-term memory extinction, suggesting that IL-1α might facilitate memory extinction. In this study, the cytokine assay using HTRF did not indicate a higher expression of hippocampal IL-1 in young mice but cortical IL-1β and IL-1α were significantly increased in adult mice. We need to investigate the role of cortical IL-1 and the local IL-1 expression in the hippocampal neurons in the future.

Post-training hippocampal NMDA receptor blockade suppresses “forgetting” in the Morris water maze spatial memory task

Post-training hippocampal NMDA receptor blockade suppresses “forgetting” in the Morris water maze spatial memory task

Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats

Although it is well established that chronic stress impairs spatial learning and memory, few studies have investigated possible ways to prevent its deleterious effects. Here, we investigated the effects of Crocus sativus L., commonly known as saffron, and its active constituent crocin on learning and memory loss and the induction of oxidative stress in the hippocampus by chronic stress. Rats were injected with saffron extract, crocin or vehicle over a period of 21 days while being exposed to chronic restraint stress (6 h/day). After this, they were trained and tested on a water-maze spatial memory task. They performed four trials per day for 5 consecutive days, and this was followed by a probe trial two days later. At the end of the behavioral testing, several parameters of oxidative stress in the hippocampus were measured. Treatment with saffron extract or crocin blocked the ability of chronic stress to impair spatial learning and memory retention. Relative to controls that received vehicle, stressed animals that received saffron extract or crocin had significantly higher levels of lipid peroxidation products, significantly higher activities of antioxidant enzymes including glutathione peroxidase, glutathione reductase and superoxide dismutase and significantly lower total antioxidant reactivity capacity. Finally, crocin significantly decreased plasma levels of corticosterone, as measured after the end of stress. These observations indicate that saffron and its active constituent crocin can prevent the impairment of learning and memory as well as the oxidative stress damage to the hippocampus induced by chronic stress. Thus, using these substances may be useful in pharmacological alleviation of cognitive deficits.

Lateral ventricle injection of the protein synthesis inhibitor anisomycin impairs long-term memory in a spatial memory task

Although protein synthesis inhibition has been shown to affect long-term memory in a wide variety of animal species, cases have been reported in which protein synthesis inhibition failed to affect memory consolidation [S. Wittstock, R. Menzel, Color learning and memory in honey bees are not affected by protein synthesis inhibition, Behav. Neural Biol., 62 (1994) 224–229.]. Most findings argue that the critical time for protein synthesis is during or immediately after training. However, other reports show a second time window, hours after training, where protein synthesis inhibition can cause amnesia [F.M. Freeman, S.P.R. Rose, A.B. Scholey, Two time windows of anisomycin-induced amnesia for passive avoidance training in the day-old chick, Neurobiol. Learn. Mem., 63 (1995) 291–295.][G. Grecksch, H. Matthies, Two sensitive periods for the amnesic effect of anisomycin, Pharmacol. Biochem. Behav., 12 (1980) 663–665.]. In this study, we addressed two questions: (1) Is protein synthesis essential for spatial memory? and (2) At what injection time window(s) will protein synthesis inhibition cause spatial memory amnesia? We report that bilateral intraventricular microinjection of anisomycin (Ani) impairs consolidation of long-term memory, in the hippocampal-dependent Morris water maze spatial memory task. Memory was impaired in a dose-dependent manner without affecting short-term memory. Spatial memory was affected only if Ani was injected 20 min before performing the task and not in any other time window before or after the behavioral test. The inhibition did not affect pre-existing memories or the capability to memorize once the effect of the inhibition diminished.

Chlordiazepoxide improves the performance of septal lesioned but not hippocampal lesioned animals in a Morris maze

The effects of hippocampal and lateral septum lesions were compared in rats tested in a water maze spatial memory task, and the effect of chlordiazepoxide (CDP) was examined. There was a significant interaction for lesion and CDP in the septal lesioned subjects, with the lesioned animals performing worse than control animals, and CDP improving the performance of lesioned animals. CDP had no effect on impaired performance in hippocampal lesioned animals.

Chlordiazepoxide improves the performance of septal lesioned but not hippocampal lesioned animals in a Morris maze.

The effects of hippocampal and lateral septum lesions were compared in rats tested in a water maze spatial memory task, and the effect of chlordiazepoxide (CDP) was examined. There was a significant interaction for lesion and CDP in the septal lesioned subjects, with the lesioned animals performing worse than control animals, and CDP improving the performance of lesioned animals. CDP had no effect on impaired performance in hippocampal lesioned animals.

Linopirdine (DuP 996) improves performance in several tests of learning and memory by modulation of cholinergic neurotransmission

The actions of linopirdine (DuP 996; 3,3- bis[4-pyrindinylmethyl]-1-phenylindolin-2-one) were evaluated in rats and mice in several cognitive behavioral tests, and for its effects on hippocampal acetylcholine (ACh) overflow in rats. Using mice treated with the muscarinic receptor antagonist, scopolamine, we studied the effects of linopiridine on retention of a passive avoidance task. Linopirdine (0.1 and 1 mg/kg) ameliorated the scopolamine-induced deficit, but at doses ranging from 0.01–1 mg/kg, it did not affect passive avoidance retention in normal (untreated) mice. In a scopolamine-induced hyperactivity test, linopirdine (1 mg/kg) decreased the motoric stimulation associated with the cholinergic hypofunction, without affecting locomotor activity on its own. Using rats, we studied the effects of linopirdine on performance in the Morris water maze spatial memory task. Young rats treated with atropine (30 mg/kg), a muscarinic receptor antagonist, took significantly longer to locate the submerged platform across 12 trials. Linopirdine (0.01 and 0.1, but not 1 mg/kg) ameliorated the atropine deficit. In addition, linopirdine (0.1 mg/kg) ameliorated the deficit in cognition-impaired aged rats (23–24 mo), but did not affect unimpaired aged rats. In terms of neurochemical action, linopirdine (1, 10, and 100 μM) produced a concentration-dependent increase in L +-evoked ACh overflow from superfused rat hippocampal slices. Also, linopirdine (10 μM) similarly increased ACh release in young control rats and cognition-impaired and nonimpaired aged rats. Our results confirm and extend findings from other studies that demonstrate the cognition-enhancing action of linopirdine in rodent models. Furthermore, these results suggest that the ACh-releasing action of linopirdine may be beneficial only when cholinergic and/or cognitive function is compromised.