Astrocyte and neuronal plasticity in the somatosensory system

Changing the whisker complement on a rodent's snout can lead to two forms of experience-dependent plasticity (EDP) in the neurons of the barrel cortex, where whiskers are somatotopically represented. One form, termed coding plasticity, concerns changes in synaptic transmission and connectivity between neurons. This is thought to underlie learning and memory processes and so adaptation to a changing environment. The second, called homeostatic plasticity, serves to maintain a restricted dynamic range of neuronal activity thus preventing its saturation or total downregulation. Current explanatory models of cortical EDP are almost exclusively neurocentric. However, in recent years, increasing evidence has emerged on the role of astrocytes in brain function, including plasticity. Indeed, astrocytes appear as necessary partners of neurons at the core of the mechanisms of coding and homeostatic plasticity recorded in neurons. In addition to neuronal plasticity, several different forms of astrocytic plasticity have recently been discovered. They extend from changes in receptor expression and dynamic changes in morphology to alteration in gliotransmitter release. It is however unclear how astrocytic plasticity contributes to the neuronal EDP. Here, we review the known and possible roles for astrocytes in the barrel cortex, including its plasticity.

Functional astrocyte-neuron lactate shuttle in a human stem cell derived neuronal network

The development of stem cell-derived neuronal networks will promote experimental system development for drug screening, toxicological testing and disease modelling, providing that they mirror closely the functional competencies of their in vivo counterparts. The NT2 cell line is one of the best documented embryocarcinoma cell lines, and can be differentiated into neurons and astrocytes. Great focus has also been placed on defining the electrophysiological properties of these cells, and more recently we have investigated the functional properties of their associated astrocytes. We now show for the first time in a human stem cell derived co-culture model that these cultures are also metabolically competent and demonstrate a functional astrocyte neuron lactate shuttle (ANLS). The ANLS hypothesis proposes that during neuronal activity, glutamate released into the synaptic cleft is taken up by astrocytes and triggers glucose uptake which is converted into lactate and released via monocarboxylate transporters for neuronal use. Using mixed cultures of NT2 derived neurons and astrocytes we have shown that these cells modulate their glucose uptake in response to glutamate, an effect that was blocked by cytochalasin B and ouabain. Additionally we demonstrate that in response to increased neuronal activity and under hypoglycaemic conditions, co-cultures modulate glycogen turnover and increase lactate production. Similar results were also shown following treatment with glutamate, potassium, Isoproterenol and dbcAMP. Together these results demonstrate for the first time a functional ANLS in a human stem cell derived co-culture.

The role of amyloid precursor protein in neuronal and non-neuronal cell lines

Models of Alzheimer’s disease (AD) have provided useful insights into the pathogenesis and mechanistic pathways that lead to its development. One emerging idea about AD is that it may be described as a hypometabolic disorder due to the reduction of glucose uptake in AD brains. Inappropriate processing of Amyloid Precursor Protein (APP) is considered central to the initiation and progression of the disease. Although the exact role of APP misprocessing is unclear, it may play a role in neuronal metabolism before the onset of neurodegeneration. To investigate the potential role of APP in neuronal metabolism, the SHSY5Y neuroblastoma cell line was used to generate cell lines that stably overexpress wild type APP695 or express Swedish mutated-APP observed in familial AD (FAD), both under the control of the neuronal promoter, Synapsin I. The effects of APP on glucose uptake, cellular stress and energy homeostasis were studied extensively. It was found that APP-overexpressing cells exhibited decreased glucose uptake with changes in basal oxygen consumption in comparison to control cell lines. Similar studies were also performed in fibroblasts taken from FAD patients compared with control fibroblasts. Previous studies found FAD-derived fibroblasts displayed altered metabolic profiles, calcium homeostasis and oxidative stress when compared to controls. As such, in this study fibroblasts were studied in terms of their ability to metabolise glucose and their mitochondrial function. Results show that FAD-derived fibroblasts demonstrate no differences in mitochondrial function, or response to oxidative stress compared to control fibroblasts. However, control fibroblasts treated with Aβ1-42 demonstrated changes in glucose uptake. This study highlights the importance of APP expression within non-neuronal cell lines, suggesting that whilst AD is considered a brain-associated disorder, peripheral effects in non-neuronal cell types should also be considered when studying the effects of Aβ on metabolism.

Diverse antiepileptic drugs increase the ratio of background synaptic inhibition to excitation and decrease neuronal excitability in neurones of the rat entorhinal cortex in vitro

Although most anti-epileptic drugs are considered to have a primary molecular target, it is clear that their actions are unlikely to be limited to effects on a single aspect of inhibitory synaptic transmission, excitatory transmission or voltage-gated ion channels. Systemically administered drugs can obviously simultaneously access all possible targets, so we have attempted to determine the overall effect of diverse agents on the balance between GABAergic inhibition, glutamatergic excitation and cellular excitability in neurones of the rat entorhinal cortex in vitro. We used an approach developed for estimating global background synaptic excitation and inhibition from fluctuations in membrane potential obtained by intracellular recordings. We have previously validated this approach in entorhinal cortical neurones [. Greenhill and Jones (2007a) Neuroscience 147:884-892]. Using this approach, we found that, despite their differing pharmacology, the drugs tested (phenytoin, lamotrigine, valproate, gabapentin, felbamate, tiagabine) were unified in their ability to increase the ratio of background GABAergic inhibition to glutamatergic excitation. This could occur as a result of decreased excitation concurrent with increased inhibition (phenytoin, lamotrigine, valproate), a decrease in excitation alone (gabapentin, felbamate), or even with a differential increase in both (tiagabine). Additionally, we found that the effects on global synaptic conductances agreed well with whole cell patch recordings of spontaneous glutamate and GABA release (our previous studies and further data presented here). The consistency with which the synaptic inhibition:excitation ratio was increased by the antiepileptic drugs tested was matched by an ability of all drugs to concurrently reduce intrinsic neuronal excitability. Thus, it seems possible that specific molecular targets among antiepileptic drugs are less important than the ability to increase the inhibition:excitation ratio and reduce overall neuronal and network excitability. © 2010 IBRO.

Spatial patterns of neuronal cytoplasmic inclusions in the tauopathies: A comparative study of five disorders

The tauopathies are a major molecular group of neurodegenerative disorders characterised by the deposition of abnormal cellular aggregates of the microtubule associated protein (MAP) tau in the form of neuronal cytoplasmic inclusions (NCI). Recent research suggests that cell to cell propagation of pathogenic tau may be involved in the neurodegeneration of these disorders. If pathogenic tau spreads along anatomical pathways it may give rise to specific spatial patterns of the NCI in brain tissue. To test this hypothesis, the spatial patterns of NCI in cerebral cortical regions were compared in tissue sections taken from five major tauopathies: (1) argyrophilic grain disease (AGD), (2) Alzheimer's disease (AD), (3) corticobasal degeneration (CBD), (4) Pick's disease (PiD), and (5) progressive supranuclear palsy (PSP). In the cerebral cortex of these disorders, NCI were frequently aggregated into clusters and the clusters were regularly distributed parallel to the pia mater. In a significant proportion of regions, the mean size of the regularly distributed clusters of NCI was in the range 400 – 800 m, measured parallel to the pia mater, approximating to the dimension of cell columns associated with the cortico-cortical anatomical pathways. Hence, the data suggest that cortical NCI in the tauopathies exhibit a spatial pattern in the cortex which could result from the spread of pathogenic tau along anatomical pathways. Treatments designed to protect the cortex from tau propagation may therefore be applicable across several different disorders within this molecular group.

An investigation into the effects of metabolic disturbance on monocyte inflammatory response and regulation

The presence of chronic inflammation is associated with increased nutrient availability during obesity or type 2 diabetes which contributes to the development of complications such as atherosclerosis, stroke and myocardial infarction. The link between increased nutrient availability and inflammatory response remains poorly understood. The functioning of monocytes, the primary instigators of the inflammatory response was assessed in response to obesity and increased glucose availability. Monocyte microRNA expression was assessed in obese individuals prior to and up to one year after bariatric surgery. A number of microRNAs were identified to be dysregulated in obesity, some of which have previously been linked to the regulation of monocyte inflammatory responses including the microRNAs 146a-5p and 424-5p. Weight loss in response to bariatric surgery lead to the reversal of microRNA changes towards control values. In vitro treatments of THP-1 monocytes with high concentrations of D-glucose resulted in decreased intracellular NAD+:NADH ratio, decreased SIRT1 deacetylase activity and increased P65 acetylation. However the increased osmotic concentration inhibited LPS induced inflammatory response and TNFα mRNA expression. In vitro treatment of primary human monocytes with increased concentrations of D-glucose resulted in increased secretion of a number of inflammatory cytokines and increased expression of TNFα mRNA. Treatment also resulted in decreased intracellular NAD+:NADH ratio and increased binding of acetylated P65 to the TNFα promoter region. In vitro treatments of primary monocytes also replicated the altered expression of the microRNAs 146a-5p and miR-424-5p, as seen in obese individuals. In conclusion a number of changes in monocyte function were observed in response to obesity and treatment with high concentrations of D-glucose. These may lead to the dysregulation of inflammatory responses contributing to the development of co-morbidities.

Human disturbance and forest diversity in the Tansa Valley, India

We assessed the diversity of woody plants at 15 forested sites in the Tansa Valley of Thane District, in Maharashtra, India. The fewest species (11) were seen at a degraded mangrove site near the river mouth, and the greatest number (150) in the rich semi-evergreen forest on Tungar Hill. For all sites there were 141 tree, 25 shrub and 15 liana species, a total of 181 species. Excluding the mangrove site, which had no species in common with the other 14 sites, we analyzed the species distributions in detail. 2 These sites ranged in area from 4 to 30 km each, had woody floras of 89 6 6 species, and varied in intensity of human impact. Despite a history of exploitation and substantial reduction in biomass from firewood collecting, set fires and illicit tree felling, considerable plant diversity remains in the area.We found a modest increase in species richness in transects away from two villages. We observed the exploitation of the forest by the principal users, primarily of the Warli Tribe. They exploited a wide variety of forest resources (92 species), for medicines, foods, construction materials, household goods, manure and other purposes. They collected 15 items for sale. By far the single most important item collected was firewood, which dramatically reduced forest biomass within 2 km of villages. The species distributions in these forest remnants are strongly nested, mostly due to varying degrees of disturbance at individual sites. The high species diversity on Tungar Hill is most likely a relict of the earlier character of forests throughout much of the valley. It merits the highest priorities for preservation, as a refuge for Western Ghat species at the northern limits of their distributions.

A comparative analysis of school satisfaction and dropout risk of middle school students attending programs for students with emotional handicaps, severe emotional disturbance and general education students attending center schools and satellite schools

This study evaluated school satisfaction as an indicator of dropout risk of students with Emotional Handicaps (EH) and students with Severe Emotional Disturbance (SED). The students attended two different kinds of middle schools in a largely urban school district in South Florida. One hundred eight students in grade 8 (ages 13-16) participated in this study. Participants were administered the National Dropout Prevention Assessment (NDPA). Forty participants with EH and SED attended a special center school. Thirty-one participants with EH and SED attended satellite programs in a regular middle school. Thirty-seven general education participants attended the same regular middle school. Overall school satisfaction scores were generated, as well as three primary factors (school, environment and personal) and 16 subscales (school atmosphere, future income, difficulty level of classwork, teacher relationships, peer relationships, intrinsic interest in classwork, school hours, classwork stress, general attitude towards school, family influence, perceived opportunity for career, future goals, travel distance, leisure time, self-appraisal of performance, and self-esteem).^ Comparison of students with EH and SED revealed that both groups of students were rated at "low risk" of becoming dropouts on the Environmental factor and the Difficulty of Schoolwork subscale. Students with EH were rated at "caution risk" risk on the Travel Distance subscale. Students with SED were rated at "high risk" on this subscale.^ There were no significant differences in school satisfaction and dropout risk between different program delivery models. There were also no significant differences for category of students (EH, SED) by school type (center school, satellite program). All students were rated at "low risk" of dropping out of school.^ There were significant differences between general education students and students with EH and SED attending satellite programs. Students with EH and SED were rated at "caution risk" for dropping out on the Travel Distance and the Leisure Time subscales. Discussion of results, implications for practice and recommendations for further research are included. ^

Special education teachers' perspectives on teaching middle school students with severe emotional disturbance

The voices of special education teachers who educate middle school students with severe emotional disturbance (SED) have been largely unheard in the educational forum and in the discussion about raising the academic achievement of middle school students with SED. These students continue to have high attrition rates and low levels of academic achievement. This study described and analyzed the perspectives of five special education teachers regarding appropriate instructional strategies for educating middle school students with SED. It also explored these teachers' opinions concerning difficulties they experienced in raising the academic achievement of students with SED and some of the solutions for overcoming these challenges. The professional literature emphasizes the importance of teacher knowledge (Altrichter, Posch, & Somekh, 1996; Clandinin & Connelly, 1996) and also offers suggestions for appropriate instructional strategies for educating students with SED (Bauer, Keefe, & Shea, 2002; Heward, 2000; Kauffman, 2001; Polloway, Patton, & Serna 2001). ^ A qualitative case study was employed to describe and analyze the five participants' perspectives on teaching middle school students with SED. The sources of data collection were interviews, observations and analysis of documents. Data presentation was from the perspective of the participants in dialogue with the interpretations of the researcher and against the backdrop of the professional literature and the researcher's critical theory philosophy. One of the major themes that emerged from the analysis was the teachers' insistence on the students' need for discipline tempered with teacher nurturing and playfulness. One concern was the need for teacher training in current appropriate, research-based instructional strategies for educating students with SED. ^ As a result of this study, one of the recommendations made was for more rigorous standards of re-certification and professional development of certified teachers who educate students with SED. ^

The role of disturbance and resource availability in structuring plant communities

Disturbances alter competitive hierarchies by reducing populations and altering resource regimes. The interaction between disturbance and resource availability may strongly influence the structure of plant communities, as observed in the recolonization of seagrass beds in outer Florida Bay that were denuded by sea-urchin overgrazing. There is no consensus concerning the interaction between disturbance and resource availability on competition intensity (CI). On the other hand, species diversity is dependent on both factors. Peaks in species diversity have been observed to occur when both resource availability and disturbance intensity are high, thus implying that CI is low. Based on this supposition of previous models, I presented the resource-disturbance hypothesis as a graphical model to make predictions of CI as a function of both disturbance intensity and the availability of a limiting resource. The predictions of this model were tested in two experiments within a seagrass community in south Florida, in which transplants of Halodule wrightii were placed into near-monocultures of Syringodium filiforme in a full-factorial array. In the first experiment, two measures of relative CI were calculated based on the changes in the short-shoot number (SS) and of rhizome length (RHL) on the transplants. Both light and disturbance were identified as important factors, though the interaction between light * disturbance was not significant. Relative CISS ranged between 0.2 and 1.0 for the high light and high disturbance treatments and the relative CIRHL < 0 for the same treatments, though results were not significantly different due to high variability and low sample size. These results, including a contour schematic using six data points from the different treatment combinations, preliminarily suggests that the resource-disturbance hypothesis may be used may be used as a next step in developing our understanding of the mechanisms involved in structuring plant communities. Furthermore, the focus of the model is on the outcome of CI, which may be a useful predictor of changes in species diversity. Further study is needed to confirm the results of this study and validate the usefulness of this model in other systems. ^

The interactive effects of predators, resources, and disturbance on freshwater snail populations from the Everglades

The origins of population dynamics depend on interplay between abiotic and biotic factors; the relative importance of each changing across space and time. Predation is a central feature of ecological communities that removes individuals (consumption) and alters prey traits (non-consumptive). Resource quality mitigates non-consumptive predator effects by stimulating growth and reproduction. Disturbance resets predator-prey interactions by removing both. I integrate experiments, time-series analysis, and performance trials to examine the relative importance of these on the population dynamics of a snail species by studying a variety of their traits. A review of ninety-three published articles revealed that snail abundance was much less in the Everglades and similar ecosystems compared to all other freshwater ecosystems considered. Separating consumptive from non-consumptive (cues) predator effects at different phosphorous levels with an experiment determined that phosphorous stimulated, but predator cues inhibited snail growth (34% vs. 23%), activity (38% vs. 53%), and reproductive effort (99% vs. 90%) compared to controls. Cues induced taller shells and smaller openings and moved to refugia where they reduced periphyton by 8%. Consumptive predator effects were minor in comparison. In a reciprocal transplant cage experiment along a predator cue and phosphorous gradient created by a canal, snails grew 10% faster and produced 37% more eggs far from the canal (fewer cues) when fed phosphorous-enriched periphyton from near the canal. Time-series analysis at four sites and predator performance trials reveal that phosphorous-enriched regions support larger snail populations, seasonal drying removes snails at all sites, crayfish negatively affect populations in enriched regions, and molluscivorous fish consume snails in the wet season. Combining these studies reveals interplay between resources, predators, and seasonality that limit snail populations in the Everglades and lead to their low abundance compared to other freshwater ecosystems. Resource quality is emerging as the critical factor because improving resources profoundly improved growth and reproduction; seasonal drying and predation become important at times and places. This work contributes to the general understanding in ecology of the relative importance of different factors that structure populations and provides evidence that bolsters monitoring efforts to assess the Comprehensive Everglades Restoration Plan that show phosphorous enrichment is a major driver of ecosystem change.

Hurricane disturbance and recovery of energy balance, CO2 fluxes and canopy structure in a mangrove forest of the Florida Everglades

Eddy covariance (EC) estimates of carbon dioxide (CO2) fluxes and energy balance are examined to investigate the functional responses of a mature mangrove forest to a disturbance generated by Hurricane Wilma on October 24, 2005 in the Florida Everglades. At the EC site, high winds from the hurricane caused nearly 100% defoliation in the upper canopy and widespread tree mortality. Soil temperatures down to -50 cm increased, and air temperature lapse rates within the forest canopy switched from statically stable to statically unstable conditions following the disturbance. Unstable conditions allowed more efficient transport of water vapor and CO2 from the surface up to the upper canopy layer. Significant increases in latent heat fluxes (LE) and nighttime net ecosystem exchange (NEE) were also observed and sensible heat fluxes (H) as a proportion of net radiation decreased significantly in response to the disturbance. Many of these impacts persisted through much of the study period through 2009. However, local albedo and MODIS (Moderate Resolution Imaging Spectro-radiometer) data (the Enhanced Vegetation Index) indicated a substantial proportion of active leaf area recovered before the EC measurements began 1 year after the storm. Observed changes in the vertical distribution and the degree of clumping in newly emerged leaves may have affected the energy balance. Direct comparisons of daytime NEE values from before the storm and after our measurements resumed did not show substantial or consistent differences that could be attributed to the disturbance. Regression analyses on seasonal time scales were required to differentiate the storm's impact on monthly average daytime NEE from the changes caused by interannual variability in other environmental drivers. The effects of the storm were apparent on annual time scales, and CO2 uptake remained approximately 250 g C m-2 yr-1 lower in 2009 compared to the average annual values measured in 2004-2005. Dry season CO2 uptake was relatively more affected by the disturbance than wet season values. Complex leaf regeneration dynamics on damaged trees during ecosystem recovery are hypothesized to lead to the variable dry versus wet season impacts on daytime NEE. In contrast, nighttime CO2 release (i.e., nighttime respiration) was consistently and significantly greater, possibly as a result of the enhanced decomposition of litter and coarse woody debris generated by the storm, and this effect was most apparent in the wet seasons compared to the dry seasons. The largest pre- and post-storm differences in NEE coincided roughly with the delayed peak in cumulative mortality of stems in 2007-2008. Across the hurricane-impacted region, cumulative tree mortality rates were also closely correlated with declines in peat surface elevation. Mangrove forest-atmosphere interactions are interpreted with respect to the damage and recovery of stand dynamics and soil accretion processes following the hurricane.

An assessment of natural and human disturbance effects on Mexican ecosystems: current trends and research gaps

Mexico harbors more than 10% of the planet’s endemic species. However, the integrity and biodiversity of many ecosystems is experiencing rapid transformation under the influence of a wide array of human and natural disturbances. In order to disentangle the effects of human and natural disturbance regimes at different spatial and temporal scales, we selected six terrestrial (temperate montane forests, montane cloud forests, tropical rain forests, tropical semi-deciduous forests, tropical dry forests, and deserts) and four aquatic (coral reefs, mangrove forests, kelp forests and saline lakes) ecosystems. We used semiquantitative statistical methods to assess (1) the most important agents of disturbance affecting the ecosystems, (2) the vulnerability of each ecosystem to anthropogenic and natural disturbance, and (3) the differences in ecosystem disturbance regimes and their resilience. Our analysis indicates a significant variation in ecological responses, recovery capacity, and resilience among ecosystems. The constant and widespread presence of human impacts on both terrestrial and aquatic ecosystems is reflected either in reduced area coverage for most systems, or reduced productivity and biodiversity, particularly in the case of fragile ecosystems (e.g., rain forests, coral reefs). In all cases, the interaction between historical human impacts and episodic high intensity natural disturbance (e.g., hurricanes, fires) has triggered a reduction in species diversity and induced significant changes in habitat distribution or species dominance. The lack of monitoring programs assessing before/after effects of major disturbances in Mexico is one of the major limitations to quantifying the commonalities and differences of disturbance effects on ecosystem properties.

Disturbance and the rising tide: the challenge of biodiversity management on low-island ecosystems

Sea-level rise presents an imminent threat to freshwater-dependent ecosystems on small oceanic islands, which often harbor rare and endemic taxa. Conservation of these assemblages is complicated by feedbacks between sea level and recurring pulse disturbances (eg hurricanes, fire). Once sea level reaches a critical level, the transition from a landscape characterized by mesophytic upland forests and freshwater wetlands to one dominated by mangroves can occur suddenly, following a single storm-surge event. We document such a trajectory, unfolding today in the Florida Keys. With sea level projected to rise substantially during the next century, ex-situ actions may be needed to conserve individual species of special concern. However, within existing public conservation units, managers have a responsibility to conserve extant biodiversity. We propose a strategy that combines the identification and intensive management of the most defensible core sites within a broader reserve system, in which refugia for biota facing local extirpation may be sought.

Assessing the net effect of anthropogenic disturbance on aquatic communities in wetlands: community structure relative to distance from canals

Anthropogenic alterations of natural hydrology are common in wetlands and often increase water permanence, converting ephemeral habitats into permanent ones. Since aquatic organisms segregate strongly along hydroperiod gradients, added water permanence caused by canals can dramatically change the structure of aquatic communities. We examined the impact of canals on the abundance and structure of wetland communities in South Florida, USA. We sampled fishes and macroinvertebrates from marsh transects originating at canals in the central and southern Everglades. Density of all aquatic organisms sampled increased in the immediate proximity of canals, but was accompanied by few compositional changes based on analysis of relative abundance. Large fish (>8 cm), small fish (<8 >cm) and macroinvertebrates (>5 mm) increased in density within 5 m of canals. This pattern was most pronounced in the dry season, suggesting that canals may serve as dry-down refugia. Increases in aquatic animal density closely matched gradients of phosphorus enrichment that decreased with distance from canals. Thus, the most apparent impact of canals on adjacent marsh communities was as conduits for nutrients that stimulated local productivity; any impact of their role as sources of increased sources of predators was not apparent. The effect of predation close to canals was overcompensated by increased secondary productivity and/or immigration toward areas adjacent to canals in the dry season. Alternatively, the consumptive effect of predatory fishes using canals as dry-season refuges is very small or spread over the expanse of marshes with open access to canals.