scholarly journals Modeling Neural Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-37 ◽  
Author(s):  
Wim van Drongelen
Keyword(s):  
Critical Role ◽  
Network Models ◽  
Network Activity ◽  
Neural Function ◽  
Population Activity ◽  
Network Nodes ◽  
Neural Excitability ◽  
Network Function ◽  
Incomplete Datasets ◽  
Insight Into

This paper provides an overview of different types of models for studying activity of nerve cells and their networks with a special emphasis on neural oscillations. One part describes the neuronal models based on the Hodgkin and Huxley formalism first described in the 1950s. It is discussed how further simplifications of this formalism enable mathematical analysis of the process of neural excitability. The focus of the paper’s second component is on network activity. Understanding network function is one of the important frontiers remaining in neuroscience. At present, experimental techniques can only provide global recordings or samples of the activity of the huge networks that form the nervous system. Models in neuroscience can therefore play a critical role by providing a framework for integration of necessarily incomplete datasets, thereby providing insight into the mechanisms of neural function. Network models can either explicitly contain individual network nodes that model the neurons, or they can be based on representations of compound population activity. The latter approach was pioneered by Wilson and Cowan in the 1970s. Finally I provide an overview and discuss how network models are employed in the study of neuronal network pathology such as epilepsy.

scholarly journals Physiological and pathophysiological homeostasis of astroglial channel proteins by Nedd4-2

2019 ◽  
Author(s):  
Bekir Altas ◽  
Anes Ju ◽  
Hugo Cruces Solís ◽  
Samir Karaca ◽  
Jan Winchenbach ◽  
...  
Keyword(s):  
Ion Channel ◽  
Ubiquitin Ligase ◽  
Neuronal Network ◽  
Critical Role ◽  
E3 Ubiquitin Ligase ◽  
Network Activity ◽  
Missense Mutations ◽  
Network Function ◽  
Channel Proteins ◽  
Neuronal Network Activity

ABSTRACTNedd4-2 is an E3 ubiquitin ligase, missense mutation of which is related to familial epilepsy, indicating its critical role in regulating neuronal network activity. However, Nedd4-2 substrates involved in neuronal network function have yet to be identified. Using mouse lines lacking Nedd4-1 and Nedd4-2, we identified astrocytic channel proteins inwardly rectifying K+ channel 4.1 (Kir4.1) and Connexin43 as Nedd4-2 substrates. We found that the expression of Kir4.1 and Connexin43 is increased upon conditional deletion of Nedd4-2 in astrocytes, leading to an elevation of astrocytic membrane ion permeability and gap junction activity, with a consequent reduction of γ-oscillatory neuronal network activity. Interestingly, our biochemical data demonstrate that missense mutations found in familial epileptic patients produce gain-of-function of Nedd4-2 gene product. Our data reveal a process of coordinated astrocytic ion channel proteostasis that controls astrocyte function and astrocyte-dependent neuronal network activity, and elucidate a potential mechanism by which aberrant Nedd4-2 function leads to epilepsy.CONDENSED TITLEUbiquitination of Astrocytic Channels by Nedd4-2SUMMARYUbiquitination is a key regulatory machinery for protein expression. Our present work provides evidence that astrocytic ion channel proteostasis coordinated by an E3 ubiquitin ligase Nedd4-2 is of particular importance for the maintenance of neuronal network activity.

scholarly journals Combining theory, model and experiment to understand how theta rhythms are generated in the hippocampus

2017 ◽  
Author(s):  
Katie A. Ferguson ◽  
Alexandra P. Chatzikalymniou ◽  
Frances K. Skinner
Keyword(s):  
Network Models ◽  
Theory Model ◽  
Network Activity ◽  
Clear Understanding ◽  
Cell Network ◽  
Connection Probability ◽  
Computational Analyses ◽  
Insight Into

AbstractScientists have observed theta rhythms (3–12 Hz) in the hippocampus for decades, but we do not have a clear understanding of how they are generated. This is largely due to the complex, multi-scale and nonlinear nature of the brain. To obtain insight into mechanisms underlying the generation of theta rhythms, we develop cellular-based network models of the hippocampus based on a whole hippocampus in vitro preparation that spontaneously generates theta rhythms. Building on theoretical and computational analyses, we find that spike frequency adaptation and post-inhibitory rebound constitute a basis for theta generation in large, minimally connected CA1 pyramidal (PYR) cell network models with fast-firing parvalbumin-positive (PV+) inhibitory cells. The particular theta frequency is more controlled by PYR to PV+ cell interactions rather than PV+ to PYR cell ones. We identify two scenarios by which theta rhythms can emerge and they can be differentiated by the ratio of excitatory to inhibitory currents to PV+ cells, but not to PYR cells. Only one of the scenarios is consistent with data from the whole hippocampus preparation, which leads to the prediction that the connection probability from PV+ to PYR cells needs to be larger than from PYR to PV+ cells. Our models can serve as a platform on which to build and develop an understanding of in vivo theta generation, and of microcircuit dynamics in the hippocampus.SignificanceBrain rhythms have been linked to cognition and are disrupted in disease. This makes it essential to understand mechanisms underlying their generation. Theory and mathematical models help provide an understanding and generate hypotheses. Together with experiment they contribute a framework to dissect the cellular contributions to network activity. However, models are inherently biological approximations, and thus the specific experimental and theoretical context upon which they are built will shape their output. If the approximations and contexts are not taken into account, particularly when using previously constructed models, misinterpretations can arise. Here, we use both theory and microcircuit models derived from a specific experimental context to provide insight into cellular-based mechanisms involved in theta rhythm generation in the hippocampus.

scholarly journals Altered network properties in C9ORF72 repeat expansion cortical neurons are due to synaptic dysfunction

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Emma M. Perkins ◽  
Karen Burr ◽  
Poulomi Banerjee ◽  
Arpan R. Mehta ◽  
Owen Dando ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Vesicle ◽  
Cortical Neurons ◽  
Electrode Array ◽  
Repeat Expansion ◽  
Cortical Network ◽  
Synaptic Function ◽  
Network Activity ◽  
Cortical Function ◽  
Network Function

Abstract Background Physiological disturbances in cortical network excitability and plasticity are established and widespread in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients, including those harbouring the C9ORF72 repeat expansion (C9ORF72RE) mutation – the most common genetic impairment causal to ALS and FTD. Noting that perturbations in cortical function are evidenced pre-symptomatically, and that the cortex is associated with widespread pathology, cortical dysfunction is thought to be an early driver of neurodegenerative disease progression. However, our understanding of how altered network function manifests at the cellular and molecular level is not clear. Methods To address this we have generated cortical neurons from patient-derived iPSCs harbouring C9ORF72RE mutations, as well as from their isogenic expansion-corrected controls. We have established a model of network activity in these neurons using multi-electrode array electrophysiology. We have then mechanistically examined the physiological processes underpinning network dysfunction using a combination of patch-clamp electrophysiology, immunocytochemistry, pharmacology and transcriptomic profiling. Results We find that C9ORF72RE causes elevated network burst activity, associated with enhanced synaptic input, yet lower burst duration, attributable to impaired pre-synaptic vesicle dynamics. We also show that the C9ORF72RE is associated with impaired synaptic plasticity. Moreover, RNA-seq analysis revealed dysregulated molecular pathways impacting on synaptic function. All molecular, cellular and network deficits are rescued by CRISPR/Cas9 correction of C9ORF72RE. Our study provides a mechanistic view of the early dysregulated processes that underpin cortical network dysfunction in ALS-FTD. Conclusion These findings suggest synaptic pathophysiology is widespread in ALS-FTD and has an early and fundamental role in driving altered network function that is thought to contribute to neurodegenerative processes in these patients. The overall importance is the identification of previously unidentified defects in pre and postsynaptic compartments affecting synaptic plasticity, synaptic vesicle stores, and network propagation, which directly impact upon cortical function.

scholarly journals Multiscale low-dimensional motor cortical state dynamics predict naturalistic reach-and-grasp behavior

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hamidreza Abbaspourazad ◽  
Mahdi Choudhury ◽  
Yan T. Wong ◽  
Bijan Pesaran ◽  
Maryam M. Shanechi
Keyword(s):  
Neural Control ◽  
Multiple Scales ◽  
Network Activity ◽  
Neural Dynamics ◽  
Population Activity ◽  
Reach And Grasp ◽  
Spatiotemporal Scales ◽  
Motor Cortical ◽  
Low Dimensional ◽  
Low Dimensional Dynamics

AbstractMotor function depends on neural dynamics spanning multiple spatiotemporal scales of population activity, from spiking of neurons to larger-scale local field potentials (LFP). How multiple scales of low-dimensional population dynamics are related in control of movements remains unknown. Multiscale neural dynamics are especially important to study in naturalistic reach-and-grasp movements, which are relatively under-explored. We learn novel multiscale dynamical models for spike-LFP network activity in monkeys performing naturalistic reach-and-grasps. We show low-dimensional dynamics of spiking and LFP activity exhibited several principal modes, each with a unique decay-frequency characteristic. One principal mode dominantly predicted movements. Despite distinct principal modes existing at the two scales, this predictive mode was multiscale and shared between scales, and was shared across sessions and monkeys, yet did not simply replicate behavioral modes. Further, this multiscale mode’s decay-frequency explained behavior. We propose that multiscale, low-dimensional motor cortical state dynamics reflect the neural control of naturalistic reach-and-grasp behaviors.

Why Does He Do It? What Explanations Resonate During Counseling for Women in Understanding Their Partner’s Abuse?

2021 ◽  
pp. 088626052198985
Author(s):  
Sally Marsden ◽  
Cathy Humphreys ◽  
Kelsey Hegarty
Keyword(s):  
Partner Violence ◽  
Research Question ◽  
Critical Role ◽  
Mental Health Research ◽  
Individual Characteristics ◽  
Clinical Group ◽  
Structured Interviews ◽  
Women’S Perceptions ◽  
Ipv Perpetration ◽  
Insight Into

Intimate partner violence (IPV) is a complex and multifaceted problem gaining increasing attention within mental health research and practice. IPV explanations focus on both individual and systemic levels; however, it is increasingly acknowledged that a single level explanation may not be sufficient. The practices of clinical disciplines may, however, still privilege an explanation at one level over another, which will influence how they work with clients. It is likely that one such clinical group, psychologists, may play a critical role in helping victim-survivors to understand and explain their experiences of IPV. However, we were unable to find any studies focusing on women’s perceptions of psychologists’ role in this. Additionally, we know little about women victim-survivors’ perceptions of why their partners use IPV. To address these gaps, the research question for this study was: What explanations resonate during counseling for women in understanding their partner’s abuse? To explore this question, 20 women who had seen psychologists after experiencing IPV participated in semi-structured interviews. The interviews were analyzed using reflexive thematic analysis and three themes constructed from the data. The first two themes, narcissist description was helpful and not all bad all the time, showed that the women found it powerful in their healing processes when psychologists offered the opportunity to discuss their partners individual characteristics as explanations for their use of IPV. The third theme, structural explanations, showed that some of the women also reflected on wider structural contexts. Implications for clinical practice include the potential healing effect when practitioners can move along a continuum of explanation levels, covering both the inner and outer worlds. Implications for research into IPV perpetration are that women hold expertise and insight into individual perpetrators and could make valuable contributions to this field.

Science and Theology for Everyone: How Climate Science is Shaping Christianity in the UK

2021 ◽  
Vol 62 (2) ◽  
pp. 147-157
Author(s):  
Caleb Gordon ◽  
Hannah Malcolm
Keyword(s):  
Critical Role ◽  
Climate Science ◽  
Significant Shift ◽  
Christian Life ◽  
Ethical Problems ◽  
Technical Leadership ◽  
Science And Theology ◽  
The Uk ◽  
Insight Into

This article analyses the growing participation of UK Christians in climate initiatives over the last five years. In many cases, climate science is cited as a necessary consideration for the fulfilment of already-existing Christian commitments. This represents a significant shift in the ways UK Christians understand the role of dialogue between theology and the sciences; previous science and theology dialogue has usually been treated as an area of expert concern, primarily offering insight into apologetics or specific ethical problems. By contrast, the dialogue between climate science and theology has seen the emergence of non-technical leadership amid the expectation that climate science plays a critical role in re-examining the meaning of Christian life, both for individuals and as communities.

Paclitaxel Promotes Cell Apoptosis in Uterine Leiomyomas

Pharmacology ◽  
2017 ◽  
Vol 100 (5-6) ◽  
pp. 246-252 ◽  
Author(s):  
Haiping Liu ◽  
Jianye Wang ◽  
Lianbing Sheng ◽  
Yan Zhang ◽  
Ning Tang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Critical Role ◽  
Estradiol Benzoate ◽  
Uterine Leiomyomas ◽  
Health Concern ◽  
Major Health ◽  
Gynecological Tumors ◽  
Dose Limiting Toxicity ◽  
Insight Into ◽  
Apoptosis Level

Uterine leiomyomas are common clinical gynecological tumors, which are a major health concern for many women. In the current study, we aimed to investigate the effect of paclitaxel (PTX) on uterine leiomyomas. A mouse model of uterine leiomyomas was established by estradiol benzoate, followed by treatment with increasing doses of PTX. PTX showed no dose-limiting toxicity that affected the survival of mice, and was able to restore the apoptosis level of uterus tissues of the model mice to normal levels. In this study, we discovered that PTX played a critical role in promoting apoptosis in the mouse model of uterine leiomyomas, which provides a new insight into the therapy of uterine leiomyomas.

Platelets in tissue repair: control of apoptosis and interactions with regenerative cells

Blood ◽  
2013 ◽  
Vol 122 (15) ◽  
pp. 2550-2554 ◽  
Author(s):  
Meinrad Gawaz ◽  
Sebastian Vogel
Keyword(s):  
Cell Survival ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Healing Process ◽  
Critical Role ◽  
Cellular Migration ◽  
Tissue Repair And Regeneration ◽  
Primary Hemostasis ◽  
Regenerative Cells ◽  
Insight Into

Abstract Besides mediating primary hemostasis and thrombosis, platelets play a critical role in tissue repair and regeneration. They regulate fundamental mechanisms involved in the healing process including cellular migration, proliferation, and angiogenesis. Control of apoptosis/cell survival and interaction with progenitor cells, which are clinically relevant but poorly understood aspects of platelets in tissue repair, will be highlighted in this review. Gaining deeper insight into the less well-characterized molecular mechanisms is necessary to develop new therapeutic platelet-based options.

scholarly journals Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs

2018 ◽  
Author(s):  
David M. Kern ◽  
SeCheol Oh ◽  
Richard K. Hite ◽  
Stephen G. Brohawn
Keyword(s):  
Lipid Bilayers ◽  
Critical Role ◽  
Anion Channel ◽  
Lipid Binding ◽  
Channel Structure ◽  
Anion Channels ◽  
Cryo Electron Microscopy ◽  
Lipid Nanodiscs ◽  
Insight Into

AbstractHypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These channels are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A in homo- or hetero-hexameric assemblies. Here we present single-particle cryo-electron microscopy structures of LRRC8A in complex with the inhibitor DCPIB reconstituted in lipid nanodiscs. DCPIB plugs the channel like a cork in a bottle - binding in the extracellular selectivity filter and sterically occluding ion conduction. Constricted and expanded structures reveal coupled dilation of cytoplasmic LRRs and the channel pore, suggesting a mechanism for channel gating by internal stimuli. Conformational and symmetry differences between LRRC8A structures determined in detergent micelles and lipid bilayers related to reorganization of intersubunit lipid binding sites demonstrate a critical role for the membrane in determining channel structure. These results provide insight into LRRC8 gating and inhibition and the role of lipids in the structure of an ionic-strength sensing ion channel.

The Influence of Evolution upon the Functional Development of the Lateral Wall of the Nose

1987 ◽  
Vol 1 (1) ◽  
pp. 51-57
Author(s):  
Thomas C. Smersh
Keyword(s):  
Critical Role ◽  
Lateral Wall ◽  
Climatic Changes ◽  
Human Anatomy ◽  
Evolutionary Development ◽  
Anatomy And Physiology ◽  
Functional Development ◽  
Human Anatomy And Physiology ◽  
Nasal Disease ◽  
Insight Into

The nose has played a surprisingly critical role repeatedly in adaptation and survival of the vertebrate family line, in olfaction to detect food and predators, in respiration in adaptation to terrestrial existence, and in preservation of homeostasis in severe climatic changes as in the great ice ages that destroyed the giant reptiles. Most importantly to us, the study of evolutionary development will provide insight into human anatomy and physiology and is an aid in the management of medical and surgical treatment of nasal disease.

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