Neuronal Firing Sensitivity to Morphologic and Active Membrane Parameters

Both the excitability of a neuron's membrane, driven by active ion channels, and dendritic morphology contribute to neuronal firing dynamics, but the relative importance and interactions between these features remain poorly understood. Recent modeling studies have shown that different combinations of active conductances can evoke similar firing patterns, but have neglected how morphology might contribute to homeostasis. Parameterizing the morphology of a cylindrical dendrite, we introduce a novel application of mathematical sensitivity analysis that quantifies how dendritic length, diameter, and surface area influence neuronal firing, and compares these effects directly against those of active parameters. The method was applied to a model of neurons from goldfish Area II. These neurons exhibit, and likely contribute to, persistent activity in eye velocity storage, a simple model of working memory. We introduce sensitivity landscapes, defined by local sensitivity analyses of firing rate and gain to each parameter, performed globally across the parameter space. Principal directions over which sensitivity to all parameters varied most revealed intrinsic currents that most controlled model output. We found domains where different groups of parameters had the highest sensitivities, suggesting that interactions within each group shaped firing behaviors within each specific domain. Application of our method, and its characterization of which models were sensitive to general morphologic features, will lead to advances in understanding how realistic morphology participates in functional homeostasis. Significantly, we can predict which active conductances, and how many of them, will compensate for a given age- or development-related structural change, or will offset a morphologic perturbation resulting from trauma or neurodegenerative disorder, to restore normal function. Our method can be adapted to analyze any computational model. Thus, sensitivity landscapes, and the quantitative predictions they provide, can give new insight into mechanisms of homeostasis in any biological system

Air pollution dispersion from biomass stoves to neighboring homes in Mirpur, Dhaka, Bangladesh.

BACKGROUND: Indoor air pollution, including fine particulate matter (PM2.5) and carbon monoxide (CO), is a major risk factor for pneumonia and other respiratory diseases. Biomass-burning cookstoves are major contributors to PM2.5 and CO concentrations. However, high concentrations of PM2.5 (> 1000 μg/m3) have been observed in homes in Dhaka, Bangladesh that do not burn biomass. We described dispersion of PM2.5 and CO from biomass burning into nearby homes in a low-income urban area of Dhaka, Bangladesh. METHODS: We recruited 10 clusters of homes, each with one biomass-burning (index) home, and 3-4 neighboring homes that used cleaner fuels with no other major sources of PM2.5 or CO. We administered a questionnaire and recorded physical features of all homes. Over 24 h, we recorded PM2.5 and CO concentrations inside each home, near each stove, and outside one neighbor home per cluster. During 8 of these 24 h, we conducted observations for pollutant-generating activities such as cooking. For each monitor, we calculated geometric mean PM2.5 concentrations at 5-6 am (baseline), during biomass burning times, during non-cooking times, and over 24 h. We used linear regressions to describe associations between monitor location and PM2.5 and CO concentrations. RESULTS: We recruited a total of 44 homes across the 10 clusters. Geometric mean PM2.5 and CO concentrations for all monitors were lowest at baseline and highest during biomass burning. During biomass burning, linear regression showed a decreasing trend of geometric mean PM2.5 and CO concentrations from the biomass stove (326.3 μg/m3, 12.3 ppm), to index home (322.7 μg/m3, 11.2 ppm), neighbor homes sharing a wall with the index home (278.4 μg/m3, 3.6 ppm), outdoors (154.2 μg/m3, 0.7 ppm), then neighbor homes that do not share a wall with the index home (83.1 μg/m3,0.2 ppm) (p = 0.03 for PM2.5, p = 0.006 for CO). CONCLUSION: Biomass burning in one home can be a source of indoor air pollution for several homes. The impact of biomass burning on PM2.5 or CO is greatest in homes that share a wall with the biomass-burning home. Eliminating biomass burning in one home may improve air quality for several households in a community

Implementing the Five-A Model of technical refinement: Key roles of the sport psychologist

There is increasing evidence for the significant contribution provided by sport psychologists within applied coaching environments. However, this rarely considers their skills/knowledge being applied when refining athletes’ already learned and well-established motor skills. Therefore, this paper focuses on how a sport psychologist might assist a coach and athlete to implement long-term permanent and pressure proof refinements. It highlights key contributions at each stage of the Five-A Model—designed to deliver these important outcomes—providing both psychomotor and psychosocial input to the support delivery. By employing these recommendations, sport psychologists can make multiple positive contributions to completion of this challenging task

Bhlhe40 is an essential repressor of IL-10 during Mycobacterium tuberculosis infection

The cytokine IL-10 antagonizes pathways that contro

Dendritic vulnerability in neurodegenerative disease: insights from analyses of cortical pyramidal neurons in transgenic mouse models

Abstract In neurodegenerative disorders, such as Alzheimer's disease, neuronal dendrites and dendritic spines undergo significant pathological changes. Because of the determinant role of these highly dynamic structures in signaling by individual neurons and ultimately in the functionality of neuronal networks that mediate cognitive functions, a detailed understanding of these changes is of paramount importance. Mutant murine models, such as the Tg2576 APP mutant mouse and the rTg4510 tau mutant mouse have been developed to provide insight into pathogenesis involving the abnormal production and aggregation of amyloid and tau proteins, because of the key role that these proteins play in neurodegenerative disease. This review showcases the multidimensional approach taken by our collaborative group to increase understanding of pathological mechanisms in neurodegenerative disease using these mouse models. This approach includes analyses of empirical 3D morphological and electrophysiological data acquired from frontal cortical pyramidal neurons using confocal laser scanning microscopy and whole-cell patchclamp recording techniques, combined with computational modeling methodologies. These collaborative studies are designed to shed insight on the repercussions of dystrophic changes in neocortical neurons, define the cellular phenotype of differential neuronal vulnerability in relevant models of neurodegenerative disease, and provide a basis upon which to develop meaningful therapeutic strategies aimed at preventing, reversing, or compensating for neurodegenerative changes in dementia