scholarly journals HippoUnit: A software tool for the automated testing and systematic comparison of detailed models of hippocampal neurons based on electrophysiological data

2021 ◽  
Vol 17 (1) ◽  
pp. e1008114
Author(s):  
Sára Sáray ◽  
Christian A. Rössert ◽  
Shailesh Appukuttan ◽  
Rosanna Migliore ◽  
Paola Vitale ◽  
...  
Keyword(s):  
Experimental Data ◽  
Pyramidal Cell ◽  
Hippocampal Neurons ◽  
Model Building ◽  
Software Tool ◽  
Signal Propagation ◽  
Cell Types ◽  
Test Suite ◽  
Neuronal Modeling ◽  
Electrophysiological Data

Anatomically and biophysically detailed data-driven neuronal models have become widely used tools for understanding and predicting the behavior and function of neurons. Due to the increasing availability of experimental data from anatomical and electrophysiological measurements as well as the growing number of computational and software tools that enable accurate neuronal modeling, there are now a large number of different models of many cell types available in the literature. These models were usually built to capture a few important or interesting properties of the given neuron type, and it is often unknown how they would behave outside their original context. In addition, there is currently no simple way of quantitatively comparing different models regarding how closely they match specific experimental observations. This limits the evaluation, re-use and further development of the existing models. Further, the development of new models could also be significantly facilitated by the ability to rapidly test the behavior of model candidates against the relevant collection of experimental data. We address these problems for the representative case of the CA1 pyramidal cell of the rat hippocampus by developing an open-source Python test suite, which makes it possible to automatically and systematically test multiple properties of models by making quantitative comparisons between the models and electrophysiological data. The tests cover various aspects of somatic behavior, and signal propagation and integration in apical dendrites. To demonstrate the utility of our approach, we applied our tests to compare the behavior of several different rat hippocampal CA1 pyramidal cell models from the ModelDB database against electrophysiological data available in the literature, and evaluated how well these models match experimental observations in different domains. We also show how we employed the test suite to aid the development of models within the European Human Brain Project (HBP), and describe the integration of the tests into the validation framework developed in the HBP, with the aim of facilitating more reproducible and transparent model building in the neuroscience community.

scholarly journals HippoUnit: A software tool for the automated testing and systematic comparison of detailed models of hippocampal neurons based on electrophysiological data

2020 ◽  
Author(s):  
Sára Sáray ◽  
Christian A. Rössert ◽  
Shailesh Appukuttan ◽  
Rosanna Migliore ◽  
Paola Vitale ◽  
...  
Keyword(s):  
Experimental Data ◽  
Human Brain ◽  
Pyramidal Cell ◽  
Hippocampal Neurons ◽  
Model Building ◽  
Rat Hippocampus ◽  
Test Suite ◽  
Electrophysiological Data ◽  
Human Brain Project ◽  
Real Neuron

AbstractAnatomically and biophysically detailed data-driven neuronal models have become widely used tools for understanding and predicting the behavior and function of neurons. Due to the increasing availability of experimental data from anatomical and electrophysiological measurements as well as the growing number of computational and software tools that enable accurate neuronal modeling, there are now a large number of different models of many cell types available in the literature. These models were usually built to capture a few important or interesting properties of the given neuron type, and it is often unknown how they would behave outside their original context. In addition, there is currently no simple way of quantitatively comparing different models regarding how closely they match specific experimental observations. This limits the evaluation, re-use and further development of the existing models. Further, the development of new models could also be significantly facilitated by the ability to rapidly test the behavior of model candidates against the relevant collection of experimental data. We address these problems for the representative case of the CA1 pyramidal cell of the rat hippocampus by developing an open-source Python test suite, which makes it possible to automatically and systematically test multiple properties of models by making quantitative comparisons between the models and electrophysiological data. The tests cover various aspects of somatic behavior, and signal propagation and integration in apical dendrites. To demonstrate the utility of our approach, we applied our tests to compare the behavior of several different hippocampal CA1 pyramidal cell models from the ModelDB database against electrophysiological data available in the literature, and concluded that each of these models provides a good match to experimental results in some domains but not in others. We also show how we employed the test suite to aid the development of models within the European Human Brain Project (HBP), and describe the integration of the tests into the validation framework developed in the HBP, with the aim of facilitating more reproducible and transparent model building in the neuroscience community.Author summaryAnatomically and biophysically detailed neuronal models are useful tools in neuroscience because they allow the prediction of the behavior and the function of the studied cell type under circumstances that are hard to investigate experimentally. However, most detailed biophysical models have been built to capture a few selected properties of the real neuron, and it is often unknown how they would behave under different circumstances, or whether they can be used to successfully answer different scientific questions. To help the modeling community develop better neural models, and make the process of model building more reproducible and transparent, we developed a test suite that enables the comparison of the behavior of models of neurons in the rat hippocampus and their evaluation against experimental data. Applying our tests to several models available in the literature, we show that each model is able to capture some of the important properties of the real neuron but fails to match experimental data in other domains. We also use the test suite in the model development workflow of the European Human Brain Project to aid the construction of better models of hippocampal neurons and networks.

Single-unit analysis of different hippocampal cell types during classical conditioning of rabbit nictitating membrane response

1983 ◽  
Vol 50 (5) ◽  
pp. 1197-1219 ◽  
Author(s):  
T. W. Berger ◽  
P. C. Rinaldi ◽  
D. J. Weisz ◽  
R. F. Thompson
Keyword(s):  
Classical Conditioning ◽  
Pyramidal Cell ◽  
Action Potentials ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Firing Frequency ◽  
Spontaneous Firing ◽  
Nictitating Membrane ◽  
Nictitating Membrane Response ◽  
Firing Characteristics

Extracellular single-unit recordings from neurons in the CA1 and CA3 regions of the dorsal hippocampus were monitored during classical conditioning of the rabbit nictitating membrane response. Neurons were classified as different cell types using response to fornix stimulation (i.e., antidromic or orthodromic activation) and spontaneous firing characteristics as criteria. Results showed that hippocampal pyramidal neurons exhibit learning-related neural plasticity that develops gradually over the course of classical conditioning. The learning-dependent pyramidal cell response is characterized by an increase in frequency of firing within conditioning trials and a within-trial pattern of discharge that correlates strongly with amplitude-time course of the behavioral response. In contrast, pyramidal cell activity recorded from control animals given unpaired presentations of the conditioned and unconditioned stimulus (CS and UCS) does not show enhanced discharge rates with repeated stimulation. Previous studies of hippocampal cellular electrophysiology have described what has been termed a theta-cell (19-21, 45), the activity of which correlates with slow-wave theta rhythm generated in the hippocampus. Neurons classified as theta-cells in the present study exhibit responses during conditioning that are distinctly different than pyramidal cells. theta-Cells respond during paired conditioning trials with a rhythmic bursting; the between-burst interval occurs at or near 8 Hz. In addition, two different types of theta-cells were distinguishable. One type of theta-cell increases firing frequency above pretrial levels while displaying the theta bursting pattern. The other type decreases firing frequency below pretrial rates while showing a theta-locked discharge. In addition to pyramidal and theta-neurons, several other cell types recorded in or near the pyramidal cell layer could be distinguished. One cell type was distinctive in that it could be activated with a short, invariant latency following fornix stimulation, but spontaneous action potentials of such neurons could not be collided with fornix shock-induced action potentials. These neurons exhibit a different profile of spontaneous firing characteristics than those of antidromically identified pyramidal cells. Nevertheless, neurons in this noncollidable category display the same learning-dependent response as pyramidal cells. It is suggested that the noncollidable neurons represent a subpopulation of pyramidal cells that do not project an axon via the fornix but project, instead, to other limbic cortical regions.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals EEA1, a Tethering Protein of the Early Sorting Endosome, Shows a Polarized Distribution in Hippocampal Neurons, Epithelial Cells, and Fibroblasts

2000 ◽  
Vol 11 (8) ◽  
pp. 2657-2671 ◽  
Author(s):  
Jean M. Wilson ◽  
Meltsje de Hoop ◽  
Natasha Zorzi ◽  
Ban-Hock Toh ◽  
Carlos G. Dotti ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mammalian Cells ◽  
Hippocampal Neurons ◽  
Cell Types ◽  
Early Endosomes ◽  
Filamentous Material ◽  
Endocytic Vesicles ◽  
Fibroblastic Cells ◽  
Darby Canine Kidney ◽  
Endocytic Pathways

EEA1 is an early endosomal Rab5 effector protein that has been implicated in the docking of incoming endocytic vesicles before fusion with early endosomes. Because of the presence of complex endosomal pathways in polarized and nonpolarized cells, we have examined the distribution of EEA1 in diverse cell types. Ultrastructural analysis demonstrates that EEA1 is present on a subdomain of the early sorting endosome but not on clathrin-coated vesicles, consistent with a role in providing directionality to early endosomal fusion. Furthermore, EEA1 is associated with filamentous material that extends from the cytoplasmic surface of the endosomal domain, which is also consistent with a tethering/docking role for EEA1. In polarized cells (Madin-Darby canine kidney cells and hippocampal neurons), EEA1 is present on a subset of “basolateral-type” endosomal compartments, suggesting that EEA1 regulates specific endocytic pathways. In both epithelial cells and fibroblastic cells, EEA1 and a transfected apical endosomal marker, endotubin, label distinct endosomal populations. Hence, there are at least two distinct sets of early endosomes in polarized and nonpolarized mammalian cells. EEA1 could provide specificity and directionality to fusion events occurring in a subset of these endosomes in polarized and nonpolarized cells.

Experimental Data on the Function of the Interstitium of the Gonads: Experiments with Cockerels

1947 ◽  
Vol s3-88 (2) ◽  
pp. 135-150
Author(s):  
J. W. SLUITER ◽  
G. J. VAN OORDT
Keyword(s):  
Experimental Data ◽  
Connective Tissue ◽  
Leydig Cells ◽  
Cell Types ◽  
Sex Hormone ◽  
Secretory Cells ◽  
Secretory Function ◽  
Glandular Cells ◽  
Male Sex ◽  
Secondary Function

1. The relative volumes of the testes and their components of 31 cockerels, 2-200 days old, were calculated and compared with the size of their increasing head appendages (Text-figs. 1a-d, 2); in addition, the effect of gestyl-administration on testes of cockerels of this age was investigated. 2. Several types of interstitial testis-cells could be distinguished morphologically and physiologically (Text-figs. 3-6 and Pl. 1); these cell-types were studied with different techniques and counted separately. 3. The main types of the interstitial cells are: (a) Lipoid cells, totally packed with lipoid globules. These cells, which are considered by many authors as fully developed Leydig cells, are not directly connected with the production of the male sex hormone; perhaps they have a secondary function in this respect, as cholesterolderivatives are stored in these cells (Pl. 1, Text-fig. 3a). (b) Secretory cells, characterized by the absence of lipoid vacuoles and the presence of numerous granular and filamentous mitochondria. These secretory cells, which produce the male sex hormone, can be divided into secretory cells A (Text-fig. 6a) without, and secretory cells B with, one large vacuole (Text-figs. 6b, 6c, 6d). 4. A considerable and partly intercellular storage of lipoids may take place at any age in the intertubular connective tissue (Text-figs. 3-4 and Pl. 1). 5. The number of the lipoid cells depends on the nutritive conditions of the animal and the development of its testes (Text-fig. 7). 6. In older cockerels most of the glandular cells lose their secretory function and pass over into lipoid storing cells. 7. Therefore we agree with Benoit, when he denies the occurrence of a ‘secretion de luxe’, but we cannot accept the presence of a ‘parenchyme de luxe’ in the testes of older cockerels.

scholarly journals TNFα-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?

2004 ◽  
Vol 1 (3) ◽  
pp. 263-273 ◽  
Author(s):  
DMITRI LEONOUDAKIS ◽  
STEVEN P. BRAITHWAITE ◽  
MICHAEL S. BEATTIE ◽  
ERIC C. BEATTIE
Keyword(s):  
Cell Death ◽  
Inflammatory Response ◽  
Hippocampal Neurons ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cell Types ◽  
Synaptic Function ◽  
Ampar Trafficking ◽  
Novel Target

Injury and disease in the CNS increases the amount of tumor necrosis factor α (TNFα) that neurons are exposed to. This cytokine is central to the inflammatory response that occurs after injury and during prolonged CNS disease, and contributes to the process of neuronal cell death. Previous studies have addressed how long-term apoptotic-signaling pathways that are initiated by TNFα might influence these processes, but the effects of inflammation on neurons and synaptic function in the timescale of minutes after exposure are largely unexplored. Our published studies examining the effect of TNFα on trafficking of AMPA-type glutamate receptors (AMPARs) in hippocampal neurons demonstrate that glial-derived TNFα causes a rapid (<15 minute) increase in the number of neuronal, surface-localized, synaptic AMPARs leading to an increase in synaptic strength. This indicates that TNFα-signal transduction acts to facilitate increased surface localization of AMPARs from internal postsynaptic stores. Importantly, an excess of surface localized AMPARs might predispose the neuron to glutamate-mediated excitotoxicity and excessive intracellular calcium concentrations, leading to cell death. This suggests a new mechanism for excitotoxic TNFα-induced neuronal death that is initiated minutes after neurons are exposed to the products of the inflammatory response.Here we review the importance of AMPAR trafficking in normal neuronal function and how abnormalities that are mediated by glial-derived cytokines such as TNFα can be central in causing neuronal disorders. We have further investigated the effects of TNFα on different neuronal cell types and present new data from cortical and hippocampal neurons in culture. Finally, we have expanded our investigation of the temporal profile of the action of this cytokine relevant to neuronal damage. We conclude that TNFα-mediated effects on AMPAR trafficking are common in diverse neuronal cell types and very rapid in their onset. The abnormal AMPAR trafficking elicited by TNFα might present a novel target to aid the development of new neuroprotective drugs.

scholarly journals Kv2.1 cell surface clusters are insertion platforms for ion channel delivery to the plasma membrane

2012 ◽  
Vol 23 (15) ◽  
pp. 2917-2929 ◽  
Author(s):  
Emily Deutsch ◽  
Aubrey V. Weigel ◽  
Elizabeth J. Akin ◽  
Phil Fox ◽  
Gentry Hansen ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Cell Surface ◽  
Ion Channel ◽  
Protein Trafficking ◽  
Hippocampal Neurons ◽  
Surface Membrane ◽  
Cell Types ◽  
Homogeneous Surface ◽  
Hek Cells ◽  
Membrane Protein Trafficking

Voltage-gated K+ (Kv) channels regulate membrane potential in many cell types. Although the channel surface density and location must be well controlled, little is known about Kv channel delivery and retrieval on the cell surface. The Kv2.1 channel localizes to micron-sized clusters in neurons and transfected human embryonic kidney (HEK) cells, where it is nonconducting. Because Kv2.1 is postulated to be involved in soluble N-ethylmaleimide–sensitive factor attachment protein receptor–mediated membrane fusion, we examined the hypothesis that these surface clusters are specialized platforms involved in membrane protein trafficking. Total internal reflection–based fluorescence recovery after photobleaching studies and quantum dot imaging of single Kv2.1 channels revealed that Kv2.1-containing vesicles deliver cargo at the Kv2.1 surface clusters in both transfected HEK cells and hippocampal neurons. More than 85% of cytoplasmic and recycling Kv2.1 channels was delivered to the cell surface at the cluster perimeter in both cell types. At least 85% of recycling Kv1.4, which, unlike Kv2.1, has a homogeneous surface distribution, is also delivered here. Actin depolymerization resulted in Kv2.1 exocytosis at cluster-free surface membrane. These results indicate that one nonconducting function of Kv2.1 is to form microdomains involved in membrane protein trafficking. This study is the first to identify stable cell surface platforms involved in ion channel trafficking.

scholarly journals Glutamatergic modulation of auditory cortex connectivity with attentional brain networks in unpredictable perceptual environment

2019 ◽  
Author(s):  
K. Kompus ◽  
V. Volehaugen ◽  
A. Craven ◽  
K. Specht
Keyword(s):  
Predictive Model ◽  
Prediction Error ◽  
Model Building ◽  
Signal Propagation ◽  
Auditory Stimulation ◽  
Perceptual Inference ◽  
Auditory Oddball ◽  
Frontoparietal Network ◽  
Young Subjects ◽  
The Brain

AbstractIn a stable environment the brain can minimize processing required for sensory input by forming a predictive model of the surrounding world and suppressing neural response to predicted stimuli. Unpredicted stimuli lead to a prediction error signal propagation through the perceptual network, and resulting adjustment to the predictive model. The inter-regional plasticity which enables the model-building and model-adjustment is hypothesized to be mediated via glutamatergic receptors. While pharmacological challenge studies with glutamate receptor ligands have demonstrated impact on prediction-error indices, it is not clear how inter-individual differences in the glutamate system affect the prediction-error processing in non-medicated state. In the present study we examined 20 healthy young subjects with resting-state proton MRS spectroscopy to characterize glutamate+glutamine (rs-Glx) levels in their Heschl’s gyrus (HG), and related this to HG functional connectivity during a roving auditory oddball protocol. No rs-Glx effects were found within the frontotemporal prediction-error network. Larger rs-Glx signal was related to stronger connectivity between HG and bilateral inferior parietal lobule during unpredictable auditory stimulation. We also found effects of rs-Glx on the coherence of default mode network (DMN) and frontoparietal network (FPN) during unpredictable auditory stimulation. Our results demonstrate the importance of Glx in modulating long-range connections and wider networks in the brain during perceptual inference.

Software Tool for Assessment of Complexity and Variability in Physiological Signals of Respiration

2011 ◽  
Vol 1 (2) ◽  
pp. 28-53
Author(s):  
Ireneusz Jablonski ◽  
Kamil Subzda ◽  
Janusz Mroczka
Keyword(s):  
Complex System ◽  
Experimental Data ◽  
Time Series ◽  
Data Analysis ◽  
Input Signal ◽  
Software Tool ◽  
Point Of View ◽  
Software Implementation ◽  
Physiological Signals ◽  
Event Time

In this paper, the authors examine software implementation and the initial preprocessing of data and tools during the assessment of the complexity and variability of long physiological time-series. The algorithms presented advance a bigger Matlab library devoted to complex system and data analysis. Commercial software is unavailable for many of these functions and is generally unsuitable for use with multi-gigabyte datasets. Reliable inter-event time extraction from input signal is an important step for the presented considerations. Knowing the distribution of the inter-event time distances, it is possible to calculate exponents due to power-law scaling. From a methodology point of view, simulations and considerations with experimental data supported each stage of the work presented. In this paper, initial calibration of the procedures with accessible data confirmed assessments made during earlier studies, which raise objectivity of measurements planned in the future.

Robust Localization Using Identifying Codes

2009 ◽  
pp. 321-347
Author(s):  
Moshe Laifenfeld ◽  
Ari Trachtenberg ◽  
David Starobinski
Keyword(s):  
Experimental Data ◽  
Information Theory ◽  
Real Life ◽  
Signal Propagation ◽  
Identifying Codes ◽  
Sensor Failures ◽  
Robust Localization ◽  
Potential Benefits ◽  
Set Up

Various real-life environments are exceptionally harsh for signal propagation, rendering well-known trilateration techniques (e.g. GPS) unsuitable for localization. Alternative proximity-based techniques, based on placing sensors near every location of interest, can be fairly complicated to set up, and are often sensitive to sensor failures or corruptions. The authors propose a different paradigm for robust localization based on identifying codes, a concept borrowed from the information theory literature. This chapter describes theoretical and practical considerations in designing and implementing such a localization infrastructure, together with experimental data supporting the potential benefits of the proposed technique.

scholarly journals Nitric Oxide Transiently Converts Synaptic Inhibition to Excitation in Retinal Amacrine Cells

2006 ◽  
Vol 95 (5) ◽  
pp. 2866-2877 ◽  
Author(s):  
Brian Hoffpauir ◽  
Emily McMains ◽  
Evanna Gleason
Keyword(s):  
Nitric Oxide ◽  
Hippocampal Neurons ◽  
Reversal Potential ◽  
Amacrine Cells ◽  
Cell Types ◽  
Synaptic Function ◽  
Positive Shift ◽  
Gabaergic Synapses ◽  
Multiple Cell

Nitric oxide (NO) is generated by multiple cell types in the vertebrate retina, including amacrine cells. We investigate the role of NO in the modulation of synaptic function using a culture system containing identified retinal amacrine cells. We find that moderate concentrations of NO alter GABAA receptor function to produce an enhancement of the GABA-gated current. Higher concentrations of NO also enhance GABA-gated currents, but this enhancement is primarily due to a substantial positive shift in the reversal potential of the current. Several pieces of evidence, including a similar effect on glycine-gated currents, indicate that the positive shift is due to an increase in cytosolic Cl−. This change in the chloride distribution is especially significant because it can invert the sign of GABA- and glycine-gated voltage responses. Furthermore, current- and voltage-clamp recordings from synaptic pairs of GABAergic amacrine cells demonstrate that NO transiently converts signaling at GABAergic synapses from inhibition to excitation. Persistence of the NO-induced shift in ECl− in the absence of extracellular Cl− indicates that the increase in cytosolic Cl− is due to release of Cl− from an internal store. An NO-dependent release of Cl− from an internal store is also demonstrated for rat hippocampal neurons indicating that this mechanism is not restricted to the avian retina. Thus signaling in the CNS can be fundamentally altered by an NO-dependent mobilization of an internal Cl− store.

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