Doubts on the efficacy of outliers correction methods

While the utilisation of different methods of outliers correction has been shown to counteract the inferential error produced by the presence of contaminating data not belonging to the studied population; the effects produced by their utilisation when samples do not contain contaminating outliers are less clear. Here a simulation approach shows that the most popular methods of outliers correction (2 Sigma, 3 Sigma, MAD, IQR, Grubbs and winsorizing) worsen the inferential evaluation of the studied population in this condition, in particular producing an inflation of Type I error and increasing the error committed in estimating the population mean and STD. We show that those methods that have the highest efficacy in counteract the inflation of Type I and Type II errors in the presence of contaminating outliers also produce the stronger increase of false positive results in their absence, suggesting that the systematic utilisation of methods for outliers correction risk to produce more harmful than beneficial effect on statistical inference. We finally propose that the safest way to deal with the presence of outliers for statistical comparisons is the utilisation of non-parametric test

Short-Term Environmental Enrichment Enhances Adult Neurogenesis, Vascular Network and Dendritic Complexity in the Hippocampus of Type 1 Diabetic Mice

Background: Several brain disturbances have been described in association to type 1 diabetes in humans. In animal models, hippocampal pathological changes were reported together with cognitive deficits. The exposure to a variety of environmental stimuli during a certain period of time is able to prevent brain alterations and to improve learning and memory in conditions like stress, aging and neurodegenerative processes. Methodology/Principal Findings: We explored the modulation of hippocampal alterations in streptozotocin-induced type 1 diabetic mice by environmental enrichment. In diabetic mice housed in standard conditions we found a reduction of adult neurogenesis in the dentate gyrus, decreased dendritic complexity in CA1 neurons and a smaller vascular fractional area in the dentate gyrus, compared with control animals in the same housing condition. A short exposure-10 days- to an enriched environment was able to enhance proliferation, survival and dendritic arborization of newborn neurons, to recover dendritic tree length and spine density of pyramidal CA1 neurons and to increase the vascular network of the dentate gyrus in diabetic animals. Conclusions/Significance: The environmental complexity seems to constitute a strong stimulator competent to rescue th

Cholinergic modulation of synaptic transmission and plasticity

The physiological and cognitive states of the brain are influenced by variations in the activity of the cholinergic systems. For example, changes in the levels of ACh have been associated with arousal/sleep cycle, sustained and focal attention. Moreover interfering with cholinergic transmission affects learning and cellular plasticity. Despite cholinergic system exerts its action by modifying the extracellular cortical concentration of acetylcholine (ACh) few investigations have until now tested if and how variation in ACh concentrations could influence neuronal synaptic efficacy and plasticity in acute brain preparation. In order to investigate this aspect we have used a quantitative experimental approach (variations in the levels of cholinergic activity) rather than a simply qualitative (absence or presence of cholinergic activity) on rodent visual cortex slices. We found that the extracellular ACh concentration affected in opposite way cortical synaptic efficacy, producing either an enhancement or an inhibition of evoked field potentials (FPs) respectively with low or high concentrations of exogenously applied ACh. The versus of ACh modulatory action was dependent on the activity of AChE and relayed on specific subtypes of muscarinic acetylcholine receptors (mAChRs), thus linking the action of ACh to the activation of particular receptor subtypes. The demonstration of a synaptic-pathway specificity of ACh modulatory action, suggests that cholinergic release could control, in a dynamic way, the flow of cortical information. Moreover, we showed that ACh concentration in cortical tissue contributes to modulate long term changes of synaptic efficacy, such as LTP or LTD induced by specific patterns of afferent neuronal activity. We found that: 1) in the absence of muscarinic receptors activation LTP is not inducible as shown in slices treated with atropine, 2)cholinergic action on cortical L TP depends on the activation of the even (M2, M,i) mAChRs. In addition, the sign of long term change, whether L TP or LTD, appears to be depend on the endogenous level of ACh; indeed, we reported that burst stimulation of afferent neurons, in rats with reduced cortical cholinergic innervation, induces an LTD instead of LTP. These results suggest that the degree of activation of cholinergic system could control cortical the direction of synaptic plasticity in visual cortex

Doubts on the efficacy of outliers correction methods

While the utilisation of different methods of outliers correction has been shown to counteract the inferential error produced by the presence of contaminating data not belonging to the studied population; the effects produced by their utilisation when samples do not contain contaminating outliers are less clear. Here a simulation approach shows that the most popular methods of outliers correction (2 Sigma, 3 Sigma, MAD, IQR, Grubbs and winsorizing) worsen the inferential evaluation of the studied population in this condition, in particular producing an inflation of Type I error and increasing the error committed in estimating the population mean and STD. We show that those methods that have the highest efficacy in counteract the inflation of Type I and Type II errors in the presence of contaminating outliers also produce the stronger increase of false positive results in their absence, suggesting that the systematic utilisation of methods for outliers correction risk to produce more harmful than beneficial effect on statistical inference. We finally propose that the safest way to deal with the presence of outliers for statistical comparisons is the utilisation of non-parametric tests

Developmental modulation of synaptic transmission by acetylcholine in the primary visual cortex

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Activity-dependent dendritic secretion of brain-derived neurotrophic factor modulates synaptic plasticity

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Activity-dependent dendritic secretion of brain-derived neurotrophic factor modulates synaptic plasticity

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