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[Effect of lead on learn and memory and release of intracellular free Ca2+ from calcium pool in dissociated mouse hippocampal neurons].

OBJECTIVE: To study effect of lead on learn and memory and the release of intracellular free Ca2+ from calcium pool in dissociated mouse hippocampal neurons. METHODS: Using a water maze we measured the ability of spatial learning of mouses. Digesting with low concentration of trypsin and gently triturating mode were used to dissociate hippocampal neurons. Using inositol 1,4,5-triphosphate (IP3) sensitive calcium store antagonist-heparine and non-IP3 sensitive calcium store (ryanodine) antagonist-procaine to stimulate hippocampal neurons, and observed the effect of Pb2+ on [Ca2+]i of hippocampal neurons by Fura-2 double wavelength fluoremetry. RESULTS: In the Morris water maze task, results indicated that mouses having drink lead water displayed significant impairment in their performance, and this extent of impairment showed in lead concentration dependent manner. Compared with control group, in condition of none of extracellular free calcium, 25 micromol x L(-1) of Pb2+ induced markedly increase of intracellular free calcium of hippocampal neurons in mouse. Heparin (IP3 sensitive calcium store antagonist) of 30 microg x ml(-1) and procaine (non-IP3 sensitive calcium store atagonist) of 0.1 mg x ml(-1) blocked the increases of [Ca2+]i in mouse hippocampal neurons elicited by 25 micromol x L(-1) of Pb2+. CONCLUSION: Chronic exposure to lead (Pb2+) reduces the ability of spatial learing and memory of mice. High level of Pb2+ facilitated release of intracellular free calcium from IP3 sensitive and non-IP3 sensitive calcium store and induced the increases of intracellular free calcium in mouse hippocampal neurons.

Animals↗

Consolidation in human motor memory.

Learning a motor skill sets in motion neural processes that continue to evolve after practice has ended, a phenomenon known as consolidation. Here we present psychophysical evidence for this, and show that consolidation of a motor skill was disrupted when a second motor task was learned immediately after the first. There was no disruption if four hours elapsed between learning the two motor skills, with consolidation occurring gradually over this period. Previous studies in humans and other primates have found this time-dependent disruption of consolidation only in explicit memory tasks, which rely on brain structures in the medial temporal lobe. Our results indicate that motor memories, which do not depend on the medial temporal lobe, can be transformed by a similar process of consolidation. By extending the phenomenon of consolidation to motor memory, our results indicate that distinct neural systems share similar characteristics when encoding and storing new information.

Adult↗

Immunocytochemical mapping of an RDL-like GABA receptor subunit and of GABA in brain structures related to learning and memory in the cricket Acheta domesticus.

The distribution of putative RDL-like GABA receptors and of gamma-aminobutyric acid (GABA) in the brain of the adult house cricket Acheta domesticus was studied using specific antisera. Special attention was given to brain structures known to be related to learning and memory. The main immunostaining for the RDL-like GABA receptor was observed in mushroom bodies, in particular the upper part of mushroom body peduncle and the two arms of the posterior calyx. Weaker immunostaining was detected in the distal part of the peduncle and in the alpha and beta lobes. The dorso- and ventrolateral protocerebrum neuropils appeared rich in RDL-like GABA receptors. Staining was also detected in the glomeruli of the antennal lobe, as well as in the ellipsoid body of the central complex. Many neurons clustered in groups exhibit GABA-like immunoreactivity. Tracts that were strongly immunostained innervated both the calyces and the lobes of mushroom bodies. The glomeruli of the antennal lobe, the ellipsoid body, as well as neuropils of the dorso- and ventrolateral protocerebrum were also rich in GABA-like immunoreactivity. The data demonstrated a good correlation between the distribution of the GABA-like and of the RDL-like GABA receptor immunoreactivity. The prominent distribution of RDL-like GABA receptor subunits, in particular areas of mushroom bodies and antennal lobes, underlines the importance of inhibitory signals in information processing in these major integrative centers of the insect brain.

Animals↗

Effect of reversible inactivation of the supramammillary nucleus on spatial learning and memory in rats.

Memory includes processes such as acquisition, consolidation and retrieval. Reference memory (RM) and working memory (WM) are two kinds of memory that can be assessed in rodents using spatial tasks, especially using the Morris water maze. The Morris water maze is particularly sensitive to hippocampal lesions. The supramammillary nucleus (SuM) has strong links with the hippocampus and septum. The role of the SuM on spatial learning is controversial. In the present study, involvement of SuM in the different steps of spatial RM and WM was investigated in the Morris water maze using reversible inactivation of SuM with lidocaine. Lidocaine (0.5 microl, 4%) was injected into the SuM through a guide cannula implanted above the SuM. The rats were trained on RM and WM versions of the Morris water maze. SuM was inactivated before training or immediately after training or before the probe trial of retrieval tests. Reversible inactivation of the SuM impaired consolidation of RM, and of consolidation and retrieval of WM. Therefore, it seems that activity of SuM neurons plays a role in spatial RM and WM learning and memory in the rat.

Anesthetics, Local↗

[Synaptic plasticity in learning and memory].

Pavlovian conditioning has been considered as one of the principal experimental approaches to understanding such complex brain functions as learning and memory. Use-dependent alterations in synaptic efficacy are believed to form the basis for these functions. The algorithm of synapse modification proposed by D. Hebb as early as 1949 is the coincident activation of pre- and postsynaptic neurons. The present review considers the evolution of experimental protocols which were used to reveal the manifestations of Hebb-type plasticity in the synaptic inputs to neocortical and hippocampal neurons. Special attention is focused on long-term modifications of synaptic efficacy in the hippocampus as a possible neuronal mechanism of learning and the role of disinhibition in their development. The effects of various neuromodulators on hippocampal long-term potentiation are considered. It is suggested that along with their involvement in disinhibition processes these substances may control the Hebb-type plasticity through intracellular second messenger systems.

Animals↗

Age-related changes in visual acuity, learning and memory in C57BL/6J and DBA/2J mice.

The DBA/2J mouse is a model of age-related pigmentary glaucoma in humans. Visual detection, pattern discrimination and visual acuity were evaluated in DBA/2J, C57BL/6J, B6.mpc1d (a C57 congenic strain) and D2.mpc1b (a D2 congenic strain) mice at 6, 12, 18 and 24 months of age. Mice were also tested in the Morris Water Maze and olfactory discrimination learning task. At 6 months, DBA/2J and D2.mpc1b mice outperformed C57BL/6J and B6.mpc1d mice in the visual detection task and there were no strain differences in performance on the water maze. At 12, 18 and 24 months, C57BL/6J and B6.mpc1d mice outperformed DBA/2J and D2.mpc1b mice in the vision tasks and in the water maze. Strains did not differ in the olfactory learning task. Therefore, loss of visual function occurs between 6 and 12 months of age in DBA/2J mice. Strain differences in visual task performance accounted for a significant proportion of the variance in measures of learning and memory in the water maze at 12, 18 and 24 months of age.

Aging↗

Circumscribed cognitive dysfunction in middle-aged adults with type 2 diabetes.

OBJECTIVE: To examine the extent to which type 2 diabetes is associated with poorer performance on measures of learning, memory, psychomotor speed, and problem-solving in middle-aged adults. RESEARCH DESIGN AND METHODS: This cross-sectional study evaluated 50 adults (age range 34-65 years, mean 50.8) with type 2 diabetes and 50 demographically similar community control subjects without diabetes. Each subject received a thorough physical examination and a detailed neuropsychological assessment. Factor analysis was used to assign specific tests to 1 of 4 cognitive domains (learning, memory for stories, problem-solving, and psychomotor speed). Hierarchical regression analysis was used to identify demographic and biomedical variables associated with cognitive dysfunction. RESULTS: Learning, memory, and problem-solving skills were unaffected by type 2 diabetes. In contrast, psychomotor slowing was predicted by a diagnosis of diabetes (r2 change = 0.075, P < 0.002) with additional variance in psychomotor efficiency explained independently by HbA1 (r2 = 0.064, P < 0.003) and vibratory threshold (r2 = 0.112, P < 0.0001). The magnitude of psychomotor slowing on specific tests ranged from 12% (Digit Vigilance) to 23% (Grooved Pegboard). CONCLUSIONS: Middle-aged adults with type 2 diabetes manifest psychomotor slowing that is associated with poorer metabolic control, whereas learning, memory, and problem-solving skills appear to be largely intact. The development of psychomotor slowing may be a manifestation of a "central neuropathy" induced by chronic hyperglycemia.

Adult↗

Learning and memory after adrenalectomy-induced hippocampal dentate granule cell degeneration in the rat.

Adrenalectomy (ADX) of normal adult rats causes selective hippocampal dentate granule cell degeneration that is prevented by corticosterone. The ability to destroy this one hippocampal cell type noninvasively made it possible to address the role of the dentate granule cells in learning and memory. Four months after ADX, 31 of 45 rats failed to show obvious granule cell loss and displayed behavior in the Morris water maze that was similar to 16 sham-operated control rats and 16 ADX rats maintained on corticosterone throughout the study. Conversely, 14 of the 45 ADX rats experienced a loss of granule cells that varied from minimal to extensive. Although there were no obvious differences between groups in motoric and motivational characteristics or search strategies, ADX rats with moderate to extensive granule cell loss acquired place learning slightly slower than controls or ADX rats with minimal or no obvious cell loss. Furthermore, the ADX rats with moderate to extensive cell loss were temporarily impaired following alteration of either intramaze or extramaze cues compared to controls. In contrast, the rats with granule cell loss remembered an old place and learned a new place as quickly as controls. These results suggest that a normal complement of dentate granule cell may not be necessary for the acquisition or retention of spatial information in the Morris water maze.

Adrenalectomy↗

Hand-preference training in the mouse reveals key elements of its learning and memory process and resolves the phenotypic complexity in the behaviour.

Handedness in the mouse comprises 2 different behaviours. Some strains have a conditional behaviour, in that the mice learn a direction of hand preference in response to reaching for food, whereas other strains have an innate or constitutive behaviour, and prior experience has no measurable effect on their hand preference. However, hybrids from different strains have revealed both recessive and dominant forms of constitutive hand preference. We proposed that kinetic parameters of the learning process would resolve this genetic heterogeneity as well as the phenotypic complexity in the behaviour. We conducted and report here a detailed kinetic analysis of hand-preference training in the C57BL/6J strain. It revealed elements of the fundamental process of learning and long-term memory that underlies the behaviour by documenting consolidation of memory, blocking of this consolidation by an inhibitor of protein synthesis, retention of memory, and speed of learning in response to training reaches. Furthermore, speed of learning is clearly described by 2 parameters that we call "capacity" (or maximum amount of learned preference) and "ability" (or number of training reaches to achieve half the capacity). These 2 kinetic parameters can vary independently among genetically different strains that learn a preference, and we used them to demonstrate that the respective recessive and dominant forms of constitutive hand-preference may be the consequence of a true null or loss of function and a gain of function, possibly a memory regulator, in the learning process. The quantitative measures provide a sensitive and selective method to establish the fundamental learning process underlying mouse hand preference and to demonstrate empirically how genes and contextual environment shape its phenotypic complexity.

Animals↗

Effects of scopolamine on learning and memory in monkeys.

The effects of scopolamine were evaluated in monkeys responding under operant procedures designed to evaluate drug effects on learning and memory. In one procedure, responding was maintained by food presentation under a multiple schedule. One component of the multiple schedule was a repeated-acquisition task in which the discriminative stimuli for left- and right-key responses changed each session (learning). In the other component, the discriminative stimuli for responses were the same each session (performance). In both components of the multiple schedule, scopolamine produced dose-related decreases in responding; there was little evidence of differential rate-decreasing effects between components. Percent errors in learning were increased in a dose-related manner, whereas percent errors in performance were generally unaffected except at high doses, which also produced substantial decreases in response rate. These results suggest that acquisition is more sensitive to the disruptive effects of scopolamine than is performance. The second procedure utilized repeated acquisition and delayed performance as a technique to study the effects of scopolamine on memory. In this procedure, each session was divided into three phases: acquisition, delay and performance. After a 24-h delay, scopolamine had little or no effect on retention, accuracy or rate of responding. In contrast, after a 60-min delay, scopolamine decreased retention in a dose-related manner. These data suggest that scopolamine produces a greater disruptive effect on short (60-min) versus long (24-h) delays.

Animals↗

Thymectomy-induced deterioration of learning and memory in mice.

Male ddY mice were thymectomized 4 weeks after birth. Learning behaviors, tested in passive and active avoidance performances and in a spatial memory task, were significantly impaired in thymectomized mice at 10 months after thymectomy, in addition to the reduced immune response. Contents of hypothalamic norepinephrine and hypothalamic choline acetyltransferase activity were significantly increased in thymectomized mice. These results suggested that thymectomy at young adult life in mice not only impaired the immune response, but also deteriorated the learning and memory ability.

Animals↗

Lipopolysaccharide-induced microglial activation induces learning and memory deficits without neuronal cell death in rats.

We used lipopolysaccharide (LPS) to activate microglia that play an important role in the brain immune system. LPS injected into the rat hippocampus CA1 region activated microglial cells resulting in an increased production of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha in the hippocampus during the initial stage of treatment. Immunostaining for IL-1beta was increased at 6 hr after LPS injection. IL-1beta-immunopositive cells were co-localized with immunostaining for CD11b. Subacute treatment with LPS by the same route for 5 days caused long-term activation of microglia and induced learning and memory deficits in animals when examined with a step-through passive avoidance test, but histochemical analysis showed that neuronal cell death was not observed under these experimental conditions. The increased expression of the heme oxygenase-1 (HO-1) gene, an oxidative stress maker, was observed. However, the genetic expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, decreased during the course of LPS treatment. We found decreases in [3H]MK801 binding in the hippocampus CA1 region by LPS-treatment for 5 days. The data shows that glutamatergic transmission was attenuated in the LPS-treated rats. These results suggest that long-term activation of microglia induced by LPS results in a decrease of glutamatergic transmission that leads to learning and memory deficits without neuronal cell death. The physiologic significance of these findings is discussed.

Animals↗

GABA-ergic drugs: effects on conditioning, memory and learning.

In order to study the role of GABA in behaviour, various GABA-mimetic and GABA-blocking drugs were tested for their effects on a conditioned avoidance response (CAR). Sodium valproate slowed the acquisition of CAR and failed to affect the latency of a well-learned CAR, but interestingly, showed a marked anti-conflict effect similar to that of benzodiazepine-derivatives. The similarity of effects of drugs such as benzodiazepines and sodium valproate, which are postulated to potentiate GABA-ergic transmission, suggests that GABA plays a role in conditioning, memory and learning.

Aminooxyacetic Acid↗

The role of the endogenous opioid system in the effects of acupuncture on mood, behavior, learning, and memory.

Ancient and contemporary papers report that acupuncture and its variations have a considerable effect on psychological state and behavior. Evidence from experimental and clinical studies suggests that acupuncture and its variations exert a strong influence on endogenous opioids in the brain, and that the endogenous opioid system is involved in various mental functions. The author suggests that the endogenous opioid system can play the key role in the mediation of the effects of acupuncture and its variations on mood, behavior, learning, and memory. Clinical implications of this suggestion are discussed.

Acupuncture Therapy↗