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1.
Science ; 383(6685): 898-903, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38386759

RESUMO

The nearby Supernova 1987A was accompanied by a burst of neutrino emission, which indicates that a compact object (a neutron star or black hole) was formed in the explosion. There has been no direct observation of this compact object. In this work, we observe the supernova remnant with JWST spectroscopy, finding narrow infrared emission lines of argon and sulfur. The line emission is spatially unresolved and blueshifted in velocity relative to the supernova rest frame. We interpret the lines as gas illuminated by a source of ionizing photons located close to the center of the expanding ejecta. Photoionization models show that the line ratios are consistent with ionization by a cooling neutron star or a pulsar wind nebula. The velocity shift could be evidence for a neutron star natal kick.

2.
Proc Natl Acad Sci U S A ; 120(45): e2313058120, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37922329

RESUMO

The basal ganglia are important for action initiation, selection, and motor learning. The input level, the striatum, receives input preferentially from the cortex and thalamus and is to 95% composed of striatal projection neurons (SPNs) with sparse GABAergic collaterals targeting distal dendrites of neighboring SPNs, in a distance-dependent manner. The remaining 5% are GABAergic and cholinergic interneurons. Our aim here is to investigate the role of surround inhibition for the intrinsic function of the striatum. Large-scale striatal networks of 20 to 40 thousand neurons were simulated with detailed multicompartmental models of different cell types, corresponding to the size of a module of the dorsolateral striatum, like the forelimb area (mouse). The effect of surround inhibition on dendritic computation and network activity was investigated, while groups of SPNs were activated. The SPN-induced surround inhibition in distal dendrites shunted effectively the corticostriatal EPSPs. The size of dendritic plateau-like potentials within the specific dendritic segment was both reduced and enhanced by inhibition, due to the hyperpolarized membrane potential of SPNs and the reversal-potential of GABA. On a population level, the competition between two subpopulations of SPNs was found to depend on the distance between the two units, the size of each unit, the activity level in each subgroup and the dopaminergic modulation of the dSPNs and iSPNs. The SPNs provided the dominating source of inhibition within the striatum, while the fast-spiking interneuron mainly had an initial effect due to short-term synaptic plasticity as shown in with ablation of the synaptic interaction.


Assuntos
Corpo Estriado , Neurônios , Animais , Camundongos , Gânglios da Base , Corpo Estriado/metabolismo , Interneurônios/fisiologia , Neostriado , Neurônios/fisiologia
3.
Nat Commun ; 14(1): 5798, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723170

RESUMO

Biophysically detailed multi-compartment models are powerful tools to explore computational principles of the brain and also serve as a theoretical framework to generate algorithms for artificial intelligence (AI) systems. However, the expensive computational cost severely limits the applications in both the neuroscience and AI fields. The major bottleneck during simulating detailed compartment models is the ability of a simulator to solve large systems of linear equations. Here, we present a novel Dendritic Hierarchical Scheduling (DHS) method to markedly accelerate such a process. We theoretically prove that the DHS implementation is computationally optimal and accurate. This GPU-based method performs with 2-3 orders of magnitude higher speed than that of the classic serial Hines method in the conventional CPU platform. We build a DeepDendrite framework, which integrates the DHS method and the GPU computing engine of the NEURON simulator and demonstrate applications of DeepDendrite in neuroscience tasks. We investigate how spatial patterns of spine inputs affect neuronal excitability in a detailed human pyramidal neuron model with 25,000 spines. Furthermore, we provide a brief discussion on the potential of DeepDendrite for AI, specifically highlighting its ability to enable the efficient training of biophysically detailed models in typical image classification tasks.


Assuntos
Inteligência Artificial , Neurônios , Humanos , Algoritmos , Células Piramidais , Encéfalo
4.
Neuroinformatics ; 19(4): 685-701, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34282528

RESUMO

Simulation of large-scale networks of neurons is an important approach to understanding and interpreting experimental data from healthy and diseased brains. Owing to the rapid development of simulation software and the accumulation of quantitative data of different neuronal types, it is possible to predict both computational and dynamical properties of local microcircuits in a 'bottom-up' manner. Simulated data from these models can be compared with experiments and 'top-down' modelling approaches, successively bridging the scales. Here we describe an open source pipeline, using the software Snudda, for predicting microcircuit connectivity and for setting up simulations using the NEURON simulation environment in a reproducible way. We also illustrate how to further 'curate' data on single neuron morphologies acquired from public databases. This model building pipeline was used to set up a first version of a full-scale cellular level model of mouse dorsal striatum. Model components from that work are here used to illustrate the different steps that are needed when modelling subcortical nuclei, such as the basal ganglia.


Assuntos
Gânglios da Base , Neurônios , Animais , Encéfalo , Simulação por Computador , Camundongos , Software
5.
Front Cell Neurosci ; 14: 91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32372917

RESUMO

The medial entorhinal cortex (MEC) contains specialized cell types whose firing is tuned to aspects of an animal's position and orientation in the environment, reflecting a neuronal representation of space. The spatially tuned firing properties of these cells quickly emerge during the third postnatal week of development in rodents. Spontaneous synchronized network activity (SSNA) has been shown to play a crucial role in the development of neuronal circuits prior to week 3. SSNA in MEC is well described in rodents during the first postnatal week, but there are little data about its development immediately prior to eye opening and spatial exploration. Furthermore, existing data lack single-cell resolution and are not integrated across layers. In this study, we addressed the question of whether the characteristics and underlying mechanisms of SSNA during the second postnatal week resemble that of the first week or whether distinct features emerge during this period. Using a combined calcium imaging and electrophysiology approach in vitro, we confirm that in mouse MEC during the second postnatal week, SSNA persists and in fact peaks, and is dependent on ionotropic glutamatergic signaling. However, SSNA differs from that observed during the first postnatal week in two ways: First, EC does not drive network activity in the hippocampus but only in neighboring neocortex (NeoC). Second, GABA does not drive network activity but influences it in a manner that is dependent both on age and receptor type. Therefore, we conclude that while there is a partial mechanistic overlap in SSNA between the first and second postnatal weeks, unique mechanistic features do emerge during the second week, suggestive of different or additional functions of MEC within the hippocampal-entorhinal circuitry with increasing maturation.

6.
Proc Natl Acad Sci U S A ; 117(17): 9554-9565, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32321828

RESUMO

The basal ganglia play an important role in decision making and selection of action primarily based on input from cortex, thalamus, and the dopamine system. Their main input structure, striatum, is central to this process. It consists of two types of projection neurons, together representing 95% of the neurons, and 5% of interneurons, among which are the cholinergic, fast-spiking, and low threshold-spiking subtypes. The membrane properties, soma-dendritic shape, and intrastriatal and extrastriatal synaptic interactions of these neurons are quite well described in the mouse, and therefore they can be simulated in sufficient detail to capture their intrinsic properties, as well as the connectivity. We focus on simulation at the striatal cellular/microcircuit level, in which the molecular/subcellular and systems levels meet. We present a nearly full-scale model of the mouse striatum using available data on synaptic connectivity, cellular morphology, and electrophysiological properties to create a microcircuit mimicking the real network. A striatal volume is populated with reconstructed neuronal morphologies with appropriate cell densities, and then we connect neurons together based on appositions between neurites as possible synapses and constrain them further with available connectivity data. Moreover, we simulate a subset of the striatum involving 10,000 neurons, with input from cortex, thalamus, and the dopamine system, as a proof of principle. Simulation at this biological scale should serve as an invaluable tool to understand the mode of operation of this complex structure. This platform will be updated with new data and expanded to simulate the entire striatum.


Assuntos
Simulação por Computador , Corpo Estriado/fisiologia , Fenômenos Eletrofisiológicos , Modelos Biológicos , Neurônios/fisiologia , Animais , Córtex Cerebral/fisiologia , Corpo Estriado/citologia , Dopamina/metabolismo , Camundongos , Receptores Dopaminérgicos/metabolismo , Tálamo/fisiologia
7.
Nature ; 565(7739): 324-327, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30651614

RESUMO

Long γ-ray bursts are associated with energetic, broad-lined, stripped-envelope supernovae1,2 and as such mark the death of massive stars. The scarcity of such events nearby and the brightness of the γ-ray burst afterglow, which dominates the emission in the first few days after the burst, have so far prevented the study of the very early evolution of supernovae associated with γ-ray bursts3. In hydrogen-stripped supernovae that are not associated with γ-ray bursts, an excess of high-velocity (roughly 30,000 kilometres per second) material has been interpreted as a signature of a choked jet, which did not emerge from the progenitor star and instead deposited all of its energy in a thermal cocoon4. Here we report multi-epoch spectroscopic observations of the supernova SN 2017iuk, which is associated with the γ-ray burst GRB 171205A. Our spectra display features at extremely high expansion velocities (around 115,000 kilometres per second) within the first day after the burst5,6. Using spectral synthesis models developed for SN 2017iuk, we show that these features are characterized by chemical abundances that differ from those observed in the ejecta of SN 2017iuk at later times. We further show that the high-velocity features originate from the mildly relativistic hot cocoon that is generated by an ultra-relativistic jet within the γ-ray burst expanding and decelerating into the medium that surrounds the progenitor star7,8. This cocoon rapidly becomes transparent9 and is outshone by the supernova emission, which starts to dominate the emission three days after the burst.

8.
Nature ; 551(7678): 67-70, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-29094694

RESUMO

The merger of two neutron stars is predicted to give rise to three major detectable phenomena: a short burst of γ-rays, a gravitational-wave signal, and a transient optical-near-infrared source powered by the synthesis of large amounts of very heavy elements via rapid neutron capture (the r-process). Such transients, named 'macronovae' or 'kilonovae', are believed to be centres of production of rare elements such as gold and platinum. The most compelling evidence so far for a kilonova was a very faint near-infrared rebrightening in the afterglow of a short γ-ray burst at redshift z = 0.356, although findings indicating bluer events have been reported. Here we report the spectral identification and describe the physical properties of a bright kilonova associated with the gravitational-wave source GW170817 and γ-ray burst GRB 170817A associated with a galaxy at a distance of 40 megaparsecs from Earth. Using a series of spectra from ground-based observatories covering the wavelength range from the ultraviolet to the near-infrared, we find that the kilonova is characterized by rapidly expanding ejecta with spectral features similar to those predicted by current models. The ejecta is optically thick early on, with a velocity of about 0.2 times light speed, and reaches a radius of about 50 astronomical units in only 1.5 days. As the ejecta expands, broad absorption-like lines appear on the spectral continuum, indicating atomic species produced by nucleosynthesis that occurs in the post-merger fast-moving dynamical ejecta and in two slower (0.05 times light speed) wind regions. Comparison with spectral models suggests that the merger ejected 0.03 to 0.05 solar masses of material, including high-opacity lanthanides.

9.
PLoS One ; 12(6): e0178533, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28586384

RESUMO

Generation of neuronal cultures from induced pluripotent stem cells (hiPSCs) serve the studies of human brain disorders. However we lack neuronal networks with balanced excitatory-inhibitory activities, which are suitable for single cell analysis. We generated low-density networks of hPSC-derived GABAergic and glutamatergic cortical neurons. We used two different co-culture models with astrocytes. We show that these cultures have balanced excitatory-inhibitory synaptic identities using confocal microscopy, electrophysiological recordings, calcium imaging and mRNA analysis. These simple and robust protocols offer the opportunity for single-cell to multi-level analysis of patient hiPSC-derived cortical excitatory-inhibitory networks; thereby creating advanced tools to study disease mechanisms underlying neurodevelopmental disorders.


Assuntos
Astrócitos/fisiologia , Técnicas de Cocultura , Neurônios GABAérgicos/fisiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Astrócitos/citologia , Diferenciação Celular/fisiologia , Células Cultivadas , Fenômenos Eletrofisiológicos , Neurônios GABAérgicos/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Análise de Célula Única
10.
BMC Neurosci ; 16: 80, 2015 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-26590111

RESUMO

BACKGROUND: To study the mapping from the retina to the brain, typically a small region of the retina is injected with a dye, which then propagates to the retina's target structures. To determine the location of the injection, usually the retina is dissected out of the eye, flattened and then imaged, causing tears and stretching of the retina. The location of the injection is then estimated from the image of the flattened retina. Here we propose a new method that avoids dissection of the retina. RESULTS: We have developed IntactEye, a software package that uses two orthogonal images of the intact retina to locate focal injections of a dye. The two images are taken while the retina is still inside the eye. This bypasses the dissection step, avoiding unnecessary damage to the retina, and speeds up data acquisition. By using the native spherical coordinates of the eye, we avoid distortions caused by interpreting a curved structure in a flat coordinate system. Our method compares well to the projection method and to the Retistruct package, which both use the flattened retina as a starting point. We have tested the method also on synthetic data, where the injection location is known. Our method has been designed for analysing mouse retinas, where there are no visible landmarks for discerning retinal orientation, but can also be applied to retinas from other species. CONCLUSIONS: IntactEye allows the user to precisely specify the location and size of a retinal injection from two orthogonal images taken of the eye. We are solving the abstract problem of locating a point on a spherical object from two orthogonal images, which might have applications outside the field of neuroscience.


Assuntos
Corantes/administração & dosagem , Processamento de Imagem Assistida por Computador/métodos , Injeções Intraoculares , Neuroimagem/métodos , Retina/anatomia & histologia , Software , Acesso à Informação , Animais , Internet , Camundongos Endogâmicos C57BL , Modelos Biológicos
11.
Dev Neurobiol ; 75(6): 641-66, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25367067

RESUMO

Molecular and activity-based cues acting together are thought to guide retinal axons to their terminal sites in vertebrate optic tectum or superior colliculus (SC) to form an ordered map of connections. The details of mechanisms involved, and the degree to which they might interact, are still not well understood. We have developed a framework within which existing computational models can be assessed in an unbiased and quantitative manner against a set of experimental data curated from the mouse retinocollicular system. Our framework facilitates comparison between models, testing new models against known phenotypes and simulating new phenotypes in existing models. We have used this framework to assess four representative models that combine Eph/ephrin gradients and/or activity-based mechanisms and competition. Two of the models were updated from their original form to fit into our framework. The models were tested against five different phenotypes: wild type, Isl2-EphA3(ki/ki), Isl2-EphA3(ki/+), ephrin-A2,A3,A5 triple knock-out (TKO), and Math5(-/-) (Atoh7). Two models successfully reproduced the extent of the Math5(-/-) anteromedial projection, but only one of those could account for the collapse point in Isl2-EphA3(ki/+). The models needed a weak anteroposterior gradient in the SC to reproduce the residual order in the ephrin-A2,A3,A5 TKO phenotype, suggesting either an incomplete knock-out or the presence of another guidance molecule. Our article demonstrates the importance of testing retinotopic models against as full a range of phenotypes as possible, and we have made available MATLAB software, we wrote to facilitate this process.


Assuntos
Mapeamento Encefálico , Modelos Neurológicos , Neurônios/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Efrinas/genética , Efrinas/metabolismo , Genótipo , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Retina , Colículos Superiores/fisiologia
12.
Nature ; 509(7499): 201-4, 2014 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-24776800

RESUMO

Gamma-ray bursts (GRBs) are most probably powered by collimated relativistic outflows (jets) from accreting black holes at cosmological distances. Bright afterglows are produced when the outflow collides with the ambient medium. Afterglow polarization directly probes the magnetic properties of the jet when measured minutes after the burst, and it probes the geometric properties of the jet and the ambient medium when measured hours to days after the burst. High values of optical polarization detected minutes after the burst of GRB 120308A indicate the presence of large-scale ordered magnetic fields originating from the central engine (the power source of the GRB). Theoretical models predict low degrees of linear polarization and no circular polarization at late times, when the energy in the original ejecta is quickly transferred to the ambient medium and propagates farther into the medium as a blast wave. Here we report the detection of circularly polarized light in the afterglow of GRB 121024A, measured 0.15 days after the burst. We show that the circular polarization is intrinsic to the afterglow and unlikely to be produced by dust scattering or plasma propagation effects. A possible explanation is to invoke anisotropic (rather than the commonly assumed isotropic) electron pitch-angle distributions, and we suggest that new models are required to produce the complex microphysics of realistic shocks in relativistic jets.

13.
PLoS One ; 9(2): e86741, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24498280

RESUMO

Neurons form networks by growing out neurites that synaptically connect to other neurons. During this process, neurites develop complex branched trees. Interestingly, the outgrowth of neurite branches is often accompanied by the simultaneous withdrawal of other branches belonging to the same tree. This apparent competitive outgrowth between branches of the same neuron is relevant for the formation of synaptic connectivity, but the underlying mechanisms are unknown. An essential component of neurites is the cytoskeleton of microtubules, long polymers of tubulin dimers running throughout the entire neurite. To investigate whether competition between neurites can emerge from the dynamics of a resource such as tubulin, we developed a multi-compartmental model of neurite growth. In the model, tubulin is produced in the soma and transported by diffusion and active transport to the growth cones at the tip of the neurites, where it is assembled into microtubules to elongate the neurite. Just as in experimental studies, we find that the outgrowth of a neurite branch can lead to the simultaneous retraction of its neighboring branches. We show that these competitive interactions occur in simple neurite morphologies as well as in complex neurite arborizations and that in developing neurons competition for a growth resource such as tubulin can account for the differential outgrowth of neurite branches. The model predicts that competition between neurite branches decreases with path distance between growth cones, increases with path distance from growth cone to soma, and decreases with a higher rate of active transport. Together, our results suggest that competition between outgrowing neurites can already emerge from relatively simple and basic dynamics of a growth resource. Our findings point to the need to test the model predictions and to determine, by monitoring tubulin concentrations in outgrowing neurons, whether tubulin is the resource for which neurites compete.


Assuntos
Algoritmos , Cones de Crescimento/fisiologia , Modelos Neurológicos , Neuritos/fisiologia , Animais , Células Cultivadas , Simulação por Computador , Dendritos/fisiologia , Humanos , Cinética , Neurônios/citologia , Neurônios/fisiologia
14.
Sci Total Environ ; 470-471: 270-81, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24140698

RESUMO

Major gaseous and particulate pollutant levels over Europe in 2008 have been simulated using the offline-coupled WRFCMAQ chemistry and transport modeling system. The simulations are compared with surface observations from the EMEP stations, ozone (O3) soundings, ship-borne O3 and nitrogen dioxide (NO2) observations in the western Mediterranean, tropospheric NO2 vertical column densities from the SCIAMACHY instrument, and aerosol optical depths (AOD) from the AERONET. The results show that on average, surface O3 levels are underestimated by 4 to 7% over the northern European EMEP stations while they are overestimated by 7-10% over the southern European EMEP stations and underestimated in the tropospheric column (by 10-20%). Particulate matter (PM) mass concentrations are underestimated by up to 60%, particularly in southern and eastern Europe, suggesting underestimated PM sources. Larger differences are calculated for individual aerosol components, particularly for organic and elemental carbon than for the total PM mass, indicating uncertainty in the combustion sources. Better agreement has been obtained for aerosol species over urban areas of the eastern Mediterranean, particularly for nss-SO4(2), attributed to the implementation of higher quality emission inventories for that area. Simulated AOD levels are lower than the AERONET observations by 10% on average, with average underestimations of 3% north of 40°N, attributed to the low anthropogenic emissions in the model and 22% south of 40°N, suggesting underestimated natural and resuspended dust emissions. Overall, the results reveal differences in the model performance between northern and southern Europe, suggesting significant differences in the representation of both anthropogenic and natural emissions in these regions. Budget analyses indicate that O3 and peroxyacetyl nitrate (PAN) are transported from the free troposphere (FT) to the planetary boundary layer over Europe, while other species follow the reverse path and are then advected away from the source region.


Assuntos
Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental , Modelos Químicos , Europa (Continente)
15.
J Neurosci ; 33(43): 17197-208, 2013 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-24155324

RESUMO

The neocortex in our brain stores long-term memories by changing the strength of connections between neurons. To date, the rules and mechanisms that govern activity-induced synaptic changes at human cortical synapses are poorly understood and have not been studied directly at a cellular level. Here, we made whole-cell recordings of human pyramidal neurons in slices of brain tissue resected during neurosurgery to investigate spike timing-dependent synaptic plasticity in the adult human neocortex. We find that human cortical synapses can undergo bidirectional modifications in strength throughout adulthood. Both long-term potentiation and long-term depression of synapses was dependent on postsynaptic NMDA receptors. Interestingly, we find that human cortical synapses can associate presynaptic and postsynaptic events in a wide temporal window, and that rules for synaptic plasticity in human neocortex are reversed compared with what is generally found in the rodent brain. We show this is caused by dendritic L-type voltage-gated Ca2+ channels that are prominently activated during action potential firing. Activation of these channels determines whether human synapses strengthen or weaken. These findings provide a synaptic basis for the timing rules observed in human sensory and motor plasticity in vivo, and offer insights into the physiological role of L-type voltage-gated Ca2+ channels in the human brain.


Assuntos
Potenciação de Longa Duração , Depressão Sináptica de Longo Prazo , Neocórtex/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/fisiologia , Potenciais de Ação , Adolescente , Adulto , Canais de Cálcio Tipo L/metabolismo , Dendritos/metabolismo , Dendritos/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neocórtex/citologia , Neocórtex/metabolismo , Células Piramidais/metabolismo , Células Piramidais/fisiologia
16.
Vis Neurosci ; 30(4): 125-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23968139

RESUMO

We review and comment on the recent model of Grimbert and Cang of the development of topographically ordered maps from the retina to the superior colliculus. This model posits a phase in which arbors are created in zones permitted by Eph and ephrin signaling, followed by a phase in which activity-dependent synaptic plasticity refines the map. We show that it is not possible to generate the arborization probability functions used in the simulations of Grimbert and Cang using gradients of Ephs and ephrins and the interaction mechanism that Grimbert and Cang propose in their results. Furthermore, the arborization probabilities we do generate are far less sharp than we imagine truly "permissive" ones would be. It remains to be seen if maps can be generated from the nonpermissive arborization probabilities generated from gradients.


Assuntos
Axônios/fisiologia , Mapeamento Encefálico , Modelos Neurológicos , Neurônios/citologia , Retina , Colículos Superiores , Animais
17.
Nature ; 500(7464): 547-9, 2013 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-23912055

RESUMO

Short-duration γ-ray bursts are intense flashes of cosmic γ-rays, lasting less than about two seconds, whose origin is unclear. The favoured hypothesis is that they are produced by a relativistic jet created by the merger of two compact stellar objects (specifically two neutron stars or a neutron star and a black hole). This is supported by indirect evidence such as the properties of their host galaxies, but unambiguous confirmation of the model is still lacking. Mergers of this kind are also expected to create significant quantities of neutron-rich radioactive species, whose decay should result in a faint transient, known as a 'kilonova', in the days following the burst. Indeed, it is speculated that this mechanism may be the predominant source of stable r-process elements in the Universe. Recent calculations suggest that much of the kilonova energy should appear in the near-infrared spectral range, because of the high optical opacity created by these heavy r-process elements. Here we report optical and near-infrared observations that provide strong evidence for such an event accompanying the short-duration γ-ray burst GRB 130603B. If this, the simplest interpretation of the data, is correct, then it confirms that compact-object mergers are the progenitors of short-duration γ-ray bursts and the sites of significant production of r-process elements. It also suggests that kilonovae offer an alternative, unbeamed electromagnetic signature of the most promising sources for direct detection of gravitational waves.

18.
J Vis Exp ; (56)2011 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-22041662

RESUMO

A hallmark pattern of activity in developing nervous systems is spontaneous, synchronized network activity. Synchronized activity has been observed in intact spinal cord, brainstem, retina, cortex and dissociated neuronal culture preparations. During periods of spontaneous activity, neurons depolarize to fire single or bursts of action potentials, activating many ion channels. Depolarization activates voltage-gated calcium channels on dendrites and spines that mediate calcium influx. Highly synchronized electrical activity has been measured from local neuronal networks using field electrodes. This technique enables high temporal sampling rates but lower spatial resolution due to integrated read-out of multiple neurons at one electrode. Single cell resolution of neuronal activity is possible using patch-clamp electrophysiology on single neurons to measure firing activity. However, the ability to measure from a network is limited to the number of neurons patched simultaneously, and typically is only one or two neurons. The use of calcium-dependent fluorescent indicator dyes has enabled the measurement of synchronized activity across a network of cells. This technique gives both high spatial resolution and sufficient temporal sampling to record spontaneous activity of the developing network. A key feature of newly-forming cortical and hippocampal networks during pre- and early postnatal development is spontaneous, synchronized neuronal activity (Katz & Shatz, 1996; Khaziphov & Luhmann, 2006). This correlated network activity is believed to be essential for the generation of functional circuits in the developing nervous system (Spitzer, 2006). In both primate and rodent brain, early electrical and calcium network waves are observed pre- and postnatally in vivo and in vitro (Adelsberger et al., 2005; Garaschuk et al., 2000; Lamblin et al., 1999). These early activity patterns, which are known to control several developmental processes including neuronal differentiation, synaptogenesis and plasticity (Rakic & Komuro, 1995; Spitzer et al., 2004) are of critical importance for the correct development and maturation of the cortical circuitry. In this JoVE video, we demonstrate the methods used to image spontaneous activity in developing cortical networks. Calcium-sensitive indicators, such as Fura 2-AM ester diffuse across the cell membrane where intracellular esterase activity cleaves the AM esters to leave the cell-impermeant form of indicator dye. The impermeant form of indicator has carboxylic acid groups which are able to then detect and bind calcium ions intracellularly. The fluorescence of the calcium-sensitive dye is transiently altered upon binding to calcium. Single or multi-photon imaging techniques are used to measure the change in photons being emitted from the dye, and thus indicate an alteration in intracellular calcium. Furthermore, these calcium-dependent indicators can be combined with other fluorescent markers to investigate cell types within the active network.


Assuntos
Cálcio/análise , Córtex Entorrinal/química , Hipocampo/química , Rede Nervosa/química , Cálcio/metabolismo , Córtex Entorrinal/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Fura-2/análogos & derivados , Fura-2/química , Fura-2/farmacocinética , Hipocampo/metabolismo , Humanos , Rede Nervosa/metabolismo
19.
Front Syst Neurosci ; 5: 57, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21808608

RESUMO

In the striatal microcircuit, fast-spiking (FS) interneurons have an important role in mediating inhibition onto neighboring medium spiny (MS) projection neurons. In this study, we combined computational modeling with in vitro and in vivo electrophysiological measurements to investigate FS cells in terms of their discharge properties and their synaptic efficacies onto MS neurons. In vivo firing of striatal FS interneurons is characterized by a high firing variability. It is not known, however, if this variability results from the input that FS cells receive, or if it is promoted by the stuttering spike behavior of these neurons. Both our model and measurements in vitro show that FS neurons that exhibit random stuttering discharge in response to steady depolarization do not show the typical stuttering behavior when they receive fluctuating input. Importantly, our model predicts that electrically coupled FS cells show substantial spike synchronization only when they are in the stuttering regime. Therefore, together with the lack of synchronized firing of striatal FS interneurons that has been reported in vivo, these results suggest that neighboring FS neurons are not in the stuttering regime simultaneously and that in vivo FS firing variability is more likely determined by the input fluctuations. Furthermore, the variability in FS firing is translated to variability in the postsynaptic amplitudes in MS neurons due to the strong synaptic depression of the FS-to-MS synapse. Our results support the idea that these synapses operate over a wide range from strongly depressed to almost fully recovered. The strong inhibitory effects that FS cells can impose on their postsynaptic targets, and the fact that the FS-to-MS synapse model showed substantial depression over extended periods of time might indicate the importance of cooperative effects of multiple presynaptic FS interneurons and the precise orchestration of their activity.

20.
Science ; 333(6039): 199-202, 2011 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-21680811

RESUMO

Variable x-ray and γ-ray emission is characteristic of the most extreme physical processes in the universe. We present multiwavelength observations of a unique γ-ray-selected transient detected by the Swift satellite, accompanied by bright emission across the electromagnetic spectrum, and whose properties are unlike any previously observed source. We pinpoint the event to the center of a small, star-forming galaxy at redshift z = 0.3534. Its high-energy emission has lasted much longer than any γ-ray burst, whereas its peak luminosity was ∼100 times higher than bright active galactic nuclei. The association of the outburst with the center of its host galaxy suggests that this phenomenon has its origin in a rare mechanism involving the massive black hole in the nucleus of that galaxy.

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