scholarly journals Active dendrites regulate the impact of gliotransmission on rat hippocampal pyramidal neurons

2016 ◽  
Vol 113 (23) ◽  
pp. E3280-E3289 ◽  
Author(s):  
Sufyan Ashhad ◽  
Rishikesh Narayanan
Keyword(s):  
Computational Models ◽  
Pyramidal Neurons ◽  
Cell Formation ◽  
Spatial Dynamics ◽  
Signaling Mechanism ◽  
Pharmacological Agents ◽  
Hippocampal Pyramidal Neurons ◽  
Spatial Spread ◽  
Active Dendrites ◽  
The Impact

An important consequence of gliotransmission, a signaling mechanism that involves glial release of active transmitter molecules, is its manifestation as N-methyl-d-aspartate receptor (NMDAR)-dependent slow inward currents in neurons. However, the intraneuronal spatial dynamics of these events or the role of active dendrites in regulating their amplitude and spatial spread have remained unexplored. Here, we used somatic and/or dendritic recordings from rat hippocampal pyramidal neurons and demonstrate that a majority of NMDAR-dependent spontaneous slow excitatory potentials (SEP) originate at dendritic locations and are significantly attenuated through their propagation across the neuronal arbor. We substantiated the astrocytic origin of SEPs through paired neuron–astrocyte recordings, where we found that specific infusion of inositol trisphosphate (InsP3) into either distal or proximal astrocytes enhanced the amplitude and frequency of neuronal SEPs. Importantly, SEPs recorded after InsP3 infusion into distal astrocytes exhibited significantly slower kinetics compared with those recorded after proximal infusion. Furthermore, using neuron-specific infusion of pharmacological agents and morphologically realistic conductance-based computational models, we demonstrate that dendritically expressed hyperpolarization-activated cyclic-nucleotide–gated (HCN) and transient potassium channels play critical roles in regulating the strength, kinetics, and compartmentalization of neuronal SEPs. Finally, through the application of subtype-specific receptor blockers during paired neuron–astrocyte recordings, we provide evidence that GluN2B- and GluN2D-containing NMDARs predominantly mediate perisomatic and dendritic SEPs, respectively. Our results unveil an important role for active dendrites in regulating the impact of gliotransmission on neurons and suggest astrocytes as a source of dendritic plateau potentials that have been implicated in localized plasticity and place cell formation.

scholarly journals Modeling unitary fields and the single-neuron contribution to local field potentials in the hippocampus

2019 ◽  
Author(s):  
Maria Teleńczuk ◽  
Bartosz Teleńczuk ◽  
Alain Destexhe
Keyword(s):  
Local Field ◽  
Computational Models ◽  
Pyramidal Neurons ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Inhibitory Synapses ◽  
Simple Method ◽  
Hippocampal Pyramidal Neurons

AbstractSynaptic currents represent a major contribution to the local field potential (LFP) in brain tissue, but the respective contribution of excitatory and inhibitory synapses is not known. Here, we provide estimates of this contribution by using computational models of hippocampal pyramidal neurons, constrained by in vitro recordings. We focus on the unitary LFP (uLFP) generated by single neurons in the CA3 region of the hippocampus. We first reproduce experimental results for hippocampal basket cells, and in particular how inhibitory uLFP are distributed within hippocampal layers. Next, we calculate the uLFP generated by pyramidal neurons, using morphologically-reconstructed CA3 pyramidal cells. The model shows that the excitatory uLFP is of small amplitude, smaller than inhibitory uLFPs. Indeed, when the two are simulated together, inhibitory uLFPs mask excitatory uLFPs, which might create the illusion that the inhibitory field is generated by pyramidal cells. These results provide an explanation for the observation that excitatory and inhibitory uLFPs are of the same polarity, in vivo and in vitro. These results also show that somatic inhibitory currents are large contributors of the LFP, which is important information to interpret this signal. Finally, the results of our model might form the basis of a simple method to compute the LFP, which could be applied to point neurons for each cell type, thus providing a simple biologically-grounded method to calculate LFPs from neural networks.

scholarly journals Morphologically constrained modeling of spinous inhibition in the somato-sensory cortex

2020 ◽  
Author(s):  
Olivier Gemin ◽  
Pablo Serna ◽  
Nora Assendorp ◽  
Matteo Fossati ◽  
Philippe Rostaing ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Computational Models ◽  
Pyramidal Neurons ◽  
Inhibitory Synapses ◽  
Brain Circuits ◽  
Basal Dendrites ◽  
Dendritic Shaft ◽  
Intact Brain ◽  
Neuronal Types ◽  
The Impact

ABSTRACTPyramidal neurons are covered by thousands of dendritic spines receiving excitatory synaptic inputs. The ultrastructure of dendritic spines shapes signal compartmentalization but ultrastructural diversity is rarely taken into account in computational models of synaptic integration. Here, we developed a 3D correlative light-electron microscopy (3D-CLEM) approach allowing the analysis of specific populations of synapses in genetically defined neuronal types in intact brain circuits. We used it to reconstruct segments of basal dendrites of layer 2/3 pyramidal neurons of adult mouse somatosensory cortex and quantify spine ultrastructural diversity. We found that 10% of spines were dually-innervated and 38% of inhibitory synapses localized to spines. Using our morphometric data to constrain a model of synaptic signal compartmentalization, we assessed the impact of spinous versus dendritic shaft inhibition. Our results indicate that spinous inhibition is locally more efficient than shaft inhibition and that it can decouple voltage and calcium signaling, potentially impacting synaptic plasticity.

scholarly journals Unique properties of dually innervated dendritic spines in pyramidal neurons of the somatosensory cortex uncovered by 3D correlative light and electron microscopy

PLoS Biology ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. e3001375
Author(s):  
Olivier Gemin ◽  
Pablo Serna ◽  
Joseph Zamith ◽  
Nora Assendorp ◽  
Matteo Fossati ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Somatosensory Cortex ◽  
Dendritic Spines ◽  
Computational Models ◽  
Pyramidal Neurons ◽  
Light And Electron Microscopy ◽  
Inhibitory Synapses ◽  
Dendritic Shaft ◽  
Intact Brain ◽  
The Impact

Pyramidal neurons (PNs) are covered by thousands of dendritic spines receiving excitatory synaptic inputs. The ultrastructure of dendritic spines shapes signal compartmentalization, but ultrastructural diversity is rarely taken into account in computational models of synaptic integration. Here, we developed a 3D correlative light–electron microscopy (3D-CLEM) approach allowing the analysis of specific populations of synapses in genetically defined neuronal types in intact brain circuits. We used it to reconstruct segments of basal dendrites of layer 2/3 PNs of adult mouse somatosensory cortex and quantify spine ultrastructural diversity. We found that 10% of spines were dually innervated and 38% of inhibitory synapses localized to spines. Using our morphometric data to constrain a model of synaptic signal compartmentalization, we assessed the impact of spinous versus dendritic shaft inhibition. Our results indicate that spinous inhibition is locally more efficient than shaft inhibition and that it can decouple voltage and calcium signaling, potentially impacting synaptic plasticity.

scholarly journals Evaluation of the impact of compliance of precast discs of overlapping on the work of the frame of a multi-storey building

2019 ◽  
Vol 97 ◽  
pp. 04022
Author(s):  
Nikolay Trekin ◽  
Emil Kodysh ◽  
Alexander Bybka ◽  
Alexander Yamalov ◽  
Nikita Konkov
Keyword(s):  
Economic Performance ◽  
Computational Models ◽  
Precast Concrete ◽  
Building Frames ◽  
Frame Building ◽  
Numerical Studies ◽  
Frame Buildings ◽  
The Impact ◽  
Structural Solutions ◽  
Storey Building

The article provides an analysis and justification of the need to take into account the compliance of discs of overlapping and coatings when calculating frames from precast concrete structures. Previously conducted full-scale experiments showed that the rigidity of the precast overlapping with full filling of the seams, in comparison with the monolithic overlapping, decreases by 3-15 times due to the ductility of the joints. The use of refined computational models of structural solutions for frames, which take into account the compliance of the conjugations of elements, makes it possible to trace possible redistribution of efforts. Such an approach when reconstructing, it is possible to optimally select and calculate the enforcement of structure, and on new designing, to increase reliability and / or improve the economic performance of frame buildings. According to the results of analytical studies, formulas were adopted for the parameters that allow one to take into account the overall compliance of overlapping disks and coatings in computational models of building frames. Numerical studies on the computational model of a frame building made it possible to evaluate the effect of accounting for compliance on the stress-strain state of a multi-storey frame.

scholarly journals Variation in human mobility and its impact on the risk of future COVID-19 outbreaks in Taiwan

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Meng-Chun Chang ◽  
Rebecca Kahn ◽  
Yu-An Li ◽  
Cheng-Sheng Lee ◽  
Caroline O. Buckee ◽  
...  
Keyword(s):  
Disease Surveillance ◽  
Initial Conditions ◽  
Human Mobility ◽  
Human Movement ◽  
Disease Spread ◽  
Spatial Spread ◽  
Movement Data ◽  
Intercity Travel ◽  
Travel Restrictions ◽  
The Impact

Abstract Background As COVID-19 continues to spread around the world, understanding how patterns of human mobility and connectivity affect outbreak dynamics, especially before outbreaks establish locally, is critical for informing response efforts. In Taiwan, most cases to date were imported or linked to imported cases. Methods In collaboration with Facebook Data for Good, we characterized changes in movement patterns in Taiwan since February 2020, and built metapopulation models that incorporate human movement data to identify the high risk areas of disease spread and assess the potential effects of local travel restrictions in Taiwan. Results We found that mobility changed with the number of local cases in Taiwan in the past few months. For each city, we identified the most highly connected areas that may serve as sources of importation during an outbreak. We showed that the risk of an outbreak in Taiwan is enhanced if initial infections occur around holidays. Intracity travel reductions have a higher impact on the risk of an outbreak than intercity travel reductions, while intercity travel reductions can narrow the scope of the outbreak and help target resources. The timing, duration, and level of travel reduction together determine the impact of travel reductions on the number of infections, and multiple combinations of these can result in similar impact. Conclusions To prepare for the potential spread within Taiwan, we utilized Facebook’s aggregated and anonymized movement and colocation data to identify cities with higher risk of infection and regional importation. We developed an interactive application that allows users to vary inputs and assumptions and shows the spatial spread of the disease and the impact of intercity and intracity travel reduction under different initial conditions. Our results can be used readily if local transmission occurs in Taiwan after relaxation of border control, providing important insights into future disease surveillance and policies for travel restrictions.

scholarly journals Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down’s syndrome mouse model

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jesús David Urbano-Gámez ◽  
Juan José Casañas ◽  
Itziar Benito ◽  
María Luz Montesinos
Keyword(s):  
Intellectual Disability ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Therapeutic Potential ◽  
Mammalian Target Of Rapamycin ◽  
Memory Deficits ◽  
Prenatal Treatment ◽  
Hippocampal Pyramidal Neurons ◽  
Metabotropic Glutamate ◽  
Mushroom Spines

AbstractDown syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we characterize the proteome of hippocampal synaptoneurosomes (SNs) from these mice, and found a predicted alteration of synaptic plasticity pathways, including long term depression (LTD). Accordingly, mGluR-LTD (metabotropic Glutamate Receptor-LTD) is enhanced in the hippocampus of Ts1Cje mice and this is correlated with an increased proportion of a particular category of mushroom spines in hippocampal pyramidal neurons. Remarkably, prenatal treatment of these mice with rapamycin has a positive pharmacological effect on both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability.

scholarly journals Does agricultural intensification cause tipping points in ecosystem services?

2021 ◽  
Author(s):  
Stephen C. L. Watson ◽  
Adrian C. Newton ◽  
Lucy E. Ridding ◽  
Paul M. Evans ◽  
Steven Brand ◽  
...  
Keyword(s):  
Ecosystem Services ◽  
Agricultural Intensification ◽  
Spatial Dynamics ◽  
Policy Option ◽  
List Type ◽  
Tipping Points ◽  
Software Models ◽  
Non Linear ◽  
Study Interval ◽  
The Impact

Abstract Context Agricultural intensification is being widely pursued as a policy option to improve food security and human development. Yet, there is a need to understand the impact of agricultural intensification on the provision of multiple ecosystem services, and to evaluate the possible occurrence of tipping points. Objectives To quantify and assess the long-term spatial dynamics of ecosystem service (ES) provision in a landscape undergoing agricultural intensification at four time points 1930, 1950, 1980 and 2015. Determine if thresholds or tipping points in ES provision may have occurred and if there are any detectable impacts on economic development and employment. Methods We used the InVEST suite of software models together with a time series of historical land cover maps and an Input–Output model to evaluate these dynamics over an 85-year period in the county of Dorset, southern England. Results Results indicated that trends in ES were often non-linear, highlighting the potential for abrupt changes in ES provision to occur in response to slight changes in underlying drivers. Despite the fluctuations in provision of different ES, overall economic activity increased almost linearly during the study interval, in line with the increase in agricultural productivity. Conclusions Such non-linear thresholds in ES will need to be avoided in the future by approaches aiming to deliver sustainable agricultural intensification. A number of positive feedback mechanisms are identified that suggest these thresholds could be considered as tipping points. However, further research into these feedbacks is required to fully determine the occurrence of tipping points in agricultural systems.

scholarly journals Evaluation of a Coupled Model to Predict the Impact of Adaptive Behaviour in the Thermal Sensation of Occupants of Naturally Ventilated Buildings in Warm-Humid Regions

2020 ◽  
Vol 13 (1) ◽  
pp. 255
Author(s):  
Luciano C. de Faria ◽  
Marcelo A. Romero ◽  
Lúcia F. S. Pirró
Keyword(s):  
Computational Models ◽  
Thermal Sensation ◽  
Coupled Model ◽  
Adaptive Behaviour ◽  
Humid Climate ◽  
Clothing Insulation ◽  
Tropical Regions ◽  
Naturally Ventilated Buildings ◽  
Adaptive Behaviours ◽  
The Impact

Improving indoor environment quality and making urban centres in tropical regions more sustainable has become a challenge for which computational models for the prediction of thermal sensation for naturally ventilated buildings (NVBs) have major role to play. This work performed analysis on thermal sensation for non-residential NVBs located in Brazilian tropical warm-humid climate and tested the effectiveness of suggested adaptive behaviours to mitigate warm thermal sensation. The research method utilized transient computational fluid dynamics models coupled with a dynamic model for human thermophysiology to predict thermal sensation. The calculated results were validated with comparison with benchmark values from questionnaires and from field measurements. The calculated results for dynamic thermal sensation (DTS) seven-point scale showed higher agreement with the thermal sensation vote than with the predicted mean vote. The test for the suggested adaptive behaviours considered reducing clothing insulation values from 0.18 to 0.32 clo (reducing DTS from 0.1 to 0.9), increasing the air speed in 0.9 m/s (reducing DTS from 0.1 to 0.9), and applying both suggestions together (reducing DTS from 0.1 to 1.3) for five scenarios with operative temperatures spanning 34.5–24.0 °C. Results quantified the tested adaptive behaviours’ efficiency showing applicability to improve thermal sensation from slightly-warm to neutral.

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