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Impaired Learning (impaired + learning)
Selected AbstractsNeurogenesis may relate to some but not all types of hippocampal-dependent learningHIPPOCAMPUS, Issue 5 2002Tracey J. Shors Abstract The hippocampal formation generates new neurons throughout adulthood. Recent studies indicate that these cells possess the morphology and physiological properties of more established neurons. However, the function of adult generated neurons is still a matter of debate. We previously demonstrated that certain forms of associative learning can enhance the survival of new neurons and a reduction in neurogenesis coincides with impaired learning of the hippocampal-dependent task of trace eyeblink conditioning. Using the toxin methylazoxymethanol acetate (MAM) for proliferating cells, we tested whether reduction of neurogenesis affected learning and performance associated with different hippocampal dependent tasks: spatial navigation learning in a Morris water maze, fear responses to context and an explicit cue after training with a trace fear paradigm. We also examined exploratory behavior in an elevated plus maze. Rats were injected with MAM (7 mg/kg) or saline for 14 days, concurrent with BrdU, to label new neurons on days 10, 12, and 14. After treatment, groups of rats were tested in the various tasks. A significant reduction in new neurons in the adult hippocampus was associated with impaired performance in some tasks, but not with others. Specifically, treatment with the antimitotic agent reduced the amount of fear acquired after exposure to a trace fear conditioning paradigm but did not affect contextual fear conditioning or spatial navigation learning in the Morris water maze. Nor did MAM treatment affect exploration in the elevated plus maze. These results combined with previous ones suggest that neurogenesis may be associated with the formation of some but not all types of hippocampal-dependent memories. Hippocampus 2002;12:578,584. © 2002 Wiley-Liss, Inc. [source] Fustin flavonoid attenuates ,-amyloid (1,42)-induced learning impairmentJOURNAL OF NEUROSCIENCE RESEARCH, Issue 16 2009Chun-Hui Jin Abstract Natural flavonoids ameliorate amyloid-, peptide (A,)-induced neurotoxicity. We examined whether the fustin flavonoid affects A,-induced learning impairment in mice. Repeated treatment with fustin significantly attenuated A, (1,42)-induced conditioned fear and passive avoidance behaviors. This effect was comparable to that of EGb761, a standard extract of ginkgo. Fustin treatment significantly prevented decreases in acetylcholine (ACh) levels, choline acetyltransferase (ChAT) activity, and ChAT gene expression induced by A, (1,42). Fustin also consistently suppressed increases in acetyl cholinesterase (AChE) activity and AChE gene expression induced by A, (1,42). In addition, fustin significantly attenuated A, (1,42)-induced selective decreases in muscarinic M1 receptor gene expression and muscarinic M1 receptor binding activity (as determined by [3H]pirenzepine binding) by modulating extracellular signal-regulated kinase 1/2 (ERK 1/2) and cAMP response-element binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression. These effects of fustin were reversed by treatment with dicyclomine, a muscarinic M1 receptor antagonist, and SL327, a selective ERK inhibitor, but not by chelerythrine, a pan-protein kinase C (PKC) inhibitor. Taken together, our results suggest that fustin attenuates A, (1,42)-impaired learning, and that the ERK/CREB/BDNF pathway is important for the M1 receptor-mediated cognition-enhancing effects of fustin. © 2009 Wiley-Liss, Inc. [source] Defensive Copers Show a Deficit in Passive Avoidance Learning on Newman's Go/No-Go Task: Implications for Self-Deception and SocializationJOURNAL OF PERSONALITY, Issue 5 2004Matthew S. Shane High-anxious individuals, low-anxious individuals, and defensive copers completed a computerized go/no-go task, in which they learned when to press or not to press a button, in response to contingent positive and negative feedback. The duration that feedback remained onscreen was self-regulated. Defensive copers showed preferential reflection away from negative feedback, committed more passive-avoidance errors, and were characterized by impaired learning, overall. Further, the ratio of reflection on negative feedback to reflection on positive feedback directly mediated both passive-avoidance errors and overall learning. Defensive coping strategies, therefore, appear to interfere with passive avoidance learning, thereby fostering perseverative, dysfunctional action patterns by reducing knowledge gained from previous mistakes. Implications for the learning of effective socialization strategies, and for psychopathy,which is commonly characterized by similar passive-avoidance deficits,are subsequently considered. [source] Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memoryPEDIATRIC DIABETES, Issue 6 2008John I Malone Background/Objective:, We previously reported that chronic hyperglycemia, but not hypoglycemia, was associated with the reduction of neuronal size in the rat brain. We hypothesized that hyperglycemia-induced changes in neuronal structure would have negative consequences, such as impaired learning and memory. We therefore assessed the effects of hyperglycemia and hypoglycemia on neuronal dendritic structure and cognitive functioning in young rats. Design/Methods:, Experimental manipulations were conducted on male Wistar rats for 8 wk, beginning at 4 wk of age. At the completion of the treatments, all rats were trained in the radial-arm water maze, a spatial (hippocampus-dependent) learning and memory task. Three groups of rats were tested: an untreated control group, a streptozotocin-induced diabetic (STZ-D) group, and an intermittent hypoglycemic group. Following behavioral training, the brains of all animals were examined with histologic and biochemical measurements. Results:, Peripheral hyperglycemia was associated with significant increases in brain sorbitol (7.5 ± 1.6 vs. 5.84 ± 1.0 ,M/mg) and inositol (9.6 ± 1.4 vs. 7.1 ± 1.1 ,M/mg) and reduced taurine (0.65 ± 0.1 vs. 1.3 ± 0.1 mg/mg). Histologic evaluation revealed neurons with reduced dendritic branching and spine density in STZ-D rats but not in control or hypoglycemic animals. In addition, the STZ-D group exhibited impaired performance on the water maze memory test. Conclusions:, Hyperglycemia, but not hypoglycemia, was associated with adverse effects on the brain polyol pathway activity, neuronal structural changes, and impaired long-term spatial memory. This finding suggests that the hyperglycemic component of diabetes mellitus has a greater adverse effect on brain functioning than does intermittent hypoglycemia. [source] Cognitive deficits in Tsc1+/,mice in the absence of cerebral lesions and seizuresANNALS OF NEUROLOGY, Issue 6 2007Susanna M. I. Goorden MSc Objective Tuberous sclerosis complex (TSC) is characterized by brain lesions, epilepsy, increased incidence of mental retardation and autism. The causal link between lesion load and epilepsy on cognitive disabilities has been debated, and these factors explain only part of the intelligence quotient variability. A Tsc2 rat model of the disease provided evidence that the TSC genes are directly involved in neuronal function. However, these lesion- and epilepsy-free animals did not show learning deficits, leaving open the possibility that the presence of brain lesions or epilepsy is a prerequisite for the cognitive deficits to fully develop. Here, we reinvestigated the relation among cerebral lesions, epilepsy, and cognitive function using Tsc1+/,mice. Methods We used immunocytochemistry and high-resolution magnetic resonance imaging to study the presence of neuronal pathology in Tsc1+/,mice. We used the Morris water maze, fear conditioning, social interaction, and nest building test to study the presence of cognitive and social deficits. Results We observed no spontaneous seizures or cerebral lesions in the brains of Tsc1+/,mice. In addition, giant dysmorphic cells were absent, and spine number and dendritic branching appeared to be normal. Nevertheless, Tsc1+/,mice showed impaired learning in the hippocampus-sensitive versions of the learning tasks and impaired social behavior. Interpretation Tsc1+/,mice show social and cognitive deficits in the absence of apparent cerebral pathology and spontaneous seizures. These findings support a model in which haploinsufficiency for the TSC genes leads to aberrations in neuronal functioning resulting in impaired learning and social behavior. Ann Neurol 2007 [source] | |||||||||||||