Integration, coincidence detection and resonance in networks of spiking neurons expressing gamma oscillations and asynchronous states

Gamma oscillations are widely seen in the awake and sleeping cerebral cortex, but the exact role of these oscillations is still debated. Here, we used biophysical models to examine how gamma oscillations may participate to the processing of afferent stimuli. We constructed conductance-based network models of gamma oscillations, based on different cell types found in cerebral cortex. The models were adjusted to extracellular unit recordings in humans, where gamma oscillations always coexist with the asynchronous firing mode. We considered three different mechanisms to generate gamma, first a mechanism based on the interaction between pyramidal neurons and interneurons (PING), second a mechanism in which gamma is generated in interneuron networks (ING) and third, a mechanism which relies on gamma oscillations generated by pacemaker Chattering neurons (CHING). We find that all three mechanisms generate features consistent with human recordings, but that the ING mechanism is most consistent with the firing rate change inside Gamma bursts seen in the human data. We next evaluated the responsiveness and resonant properties of these networks, contrasting gamma oscillations with the asynchronous mode. We find that for both slowly-varying stimuli and precisely-timed stimuli, the responsiveness is generally lower during Gamma compared to asynchronous states, while resonant properties are similar around the Gamma band. We could not find conditions where Gamma oscillations were more responsive. We therefore predict that asynchronous states provide the highest responsiveness to external stimuli, while Gamma oscillations tend to overall diminish responsiveness.

Integration, coincidence detection and resonance in networks of spiking neurons expressing Gamma oscillations and asynchronous states

PLoS Computational Biology ◽

10.1371/journal.pcbi.1009416 ◽

2021 ◽

Vol 17 (9) ◽

pp. e1009416

Author(s):

Eduarda Susin ◽

Alain Destexhe

Keyword(s):

Cerebral Cortex ◽

Pyramidal Neurons ◽

Network Models ◽

Cell Types ◽

Gamma Oscillations ◽

Coincidence Detection ◽

Biophysical Models ◽

Firing Mode ◽

Different Cell Types ◽

Gamma oscillations are widely seen in the awake and sleeping cerebral cortex, but the exact role of these oscillations is still debated. Here, we used biophysical models to examine how Gamma oscillations may participate to the processing of afferent stimuli. We constructed conductance-based network models of Gamma oscillations, based on different cell types found in cerebral cortex. The models were adjusted to extracellular unit recordings in humans, where Gamma oscillations always coexist with the asynchronous firing mode. We considered three different mechanisms to generate Gamma, first a mechanism based on the interaction between pyramidal neurons and interneurons (PING), second a mechanism in which Gamma is generated by interneuron networks (ING) and third, a mechanism which relies on Gamma oscillations generated by pacemaker chattering neurons (CHING). We find that all three mechanisms generate features consistent with human recordings, but that the ING mechanism is most consistent with the firing rate change inside Gamma bursts seen in the human data. We next evaluated the responsiveness and resonant properties of these networks, contrasting Gamma oscillations with the asynchronous mode. We find that for both slowly-varying stimuli and precisely-timed stimuli, the responsiveness is generally lower during Gamma compared to asynchronous states, while resonant properties are similar around the Gamma band. We could not find conditions where Gamma oscillations were more responsive. We therefore predict that asynchronous states provide the highest responsiveness to external stimuli, while Gamma oscillations tend to overall diminish responsiveness.

Dendritic position is a major determinant of presynaptic strength

The Journal of Cell Biology ◽

10.1083/jcb.201112135 ◽

2012 ◽

Vol 197 (2) ◽

pp. 327-337 ◽

Cited By ~ 15

Author(s):

Arthur P.H. de Jong ◽

Sabine K. Schmitz ◽

Ruud F.G. Toonen ◽

Matthijs Verhage

Keyword(s):

Neuronal Activity ◽

Pyramidal Neurons ◽

Cell Types ◽

Synaptic Coupling ◽

Action Potential Firing ◽

Vesicle Release ◽

Postsynaptic Receptors ◽

Potential Firing ◽

Mixed Networks ◽

Different regulatory principles influence synaptic coupling between neurons, including positional principles. In dendrites of pyramidal neurons, postsynaptic sensitivity depends on synapse location, with distal synapses having the highest gain. In this paper, we investigate whether similar rules exist for presynaptic terminals in mixed networks of pyramidal and dentate gyrus (DG) neurons. Unexpectedly, distal synapses had the lowest staining intensities for vesicular proteins vGlut, vGAT, Synaptotagmin, and VAMP and for many nonvesicular proteins, including Bassoon, Munc18, and Syntaxin. Concomitantly, distal synapses displayed less vesicle release upon stimulation. This dependence of presynaptic strength on dendritic position persisted after chronically blocking action potential firing and postsynaptic receptors but was markedly reduced on DG dendrites compared with pyramidal dendrites. These data reveal a novel rule, independent of neuronal activity, which regulates presynaptic strength according to dendritic position, with the strongest terminals closest to the soma. This gradient is opposite to postsynaptic gradients observed in pyramidal dendrites, and different cell types apply this rule to a different extent.

Understanding the Relevance of DNA Methylation Changes in Immune Differentiation and Disease

Genes ◽

10.3390/genes11010110 ◽

2020 ◽

Vol 11 (1) ◽

pp. 110 ◽

Cited By ~ 7

Author(s):

Carlos de la Calle-Fabregat ◽

Octavio Morante-Palacios ◽

Esteban Ballestar

Keyword(s):

Dna Methylation ◽

Cell Types ◽

Epigenetic Modifications ◽

Human Organism ◽

Cell Phenotype ◽

Effector Cells ◽

Technological Advances ◽

And Function ◽

Different Cell Types ◽

Immune cells are one of the most complex and diverse systems in the human organism. Such diversity implies an intricate network of different cell types and interactions that are dependently interconnected. The processes by which different cell types differentiate from progenitors, mature, and finally exert their function requires an orchestrated succession of molecular processes that determine cell phenotype and function. The acquisition of these phenotypes is highly dependent on the establishment of unique epigenetic profiles that confer identity and function on the various types of effector cells. These epigenetic mechanisms integrate microenvironmental cues into the genome to establish specific transcriptional programs. Epigenetic modifications bridge environment and genome regulation and play a role in human diseases by their ability to modulate physiological programs through external stimuli. DNA methylation is one of the most ubiquitous, stable, and widely studied epigenetic modifications. Recent technological advances have facilitated the generation of a vast amount of genome-wide DNA methylation data, providing profound insights into the roles of DNA methylation in health and disease. This review considers the relevance of DNA methylation to immune system cellular development and function, as well as the participation of DNA methylation defects in immune-mediated pathologies, illustrated by selected paradigmatic diseases.

Histone modification dynamics as revealed by multicolor immunofluorescence-based single-cell analysis

Journal of Cell Science ◽

10.1242/jcs.243444 ◽

2020 ◽

Vol 133 (14) ◽

pp. jcs243444 ◽

Cited By ~ 1

Author(s):

Yoko Hayashi-Takanaka ◽

Yuto Kina ◽

Fumiaki Nakamura ◽

Leontine E. Becking ◽

Yoichi Nakao ◽

...

Keyword(s):

Cell Cycle ◽

Histone Modifications ◽

Histone Deacetylases ◽

Single Cell Analysis ◽

Single Cells ◽

Cell Types ◽

Transient Overexpression ◽

Overexpression System ◽

Different Cell Types ◽

ABSTRACTPost-translational modifications on histones can be stable epigenetic marks or transient signals that can occur in response to internal and external stimuli. Levels of histone modifications fluctuate during the cell cycle and vary among different cell types. Here, we describe a simple system to monitor the levels of multiple histone modifications in single cells by multicolor immunofluorescence using directly labeled modification-specific antibodies. We analyzed histone H3 and H4 modifications during the cell cycle. Levels of active marks, such as acetylation and H3K4 methylation, were increased during the S phase, in association with chromatin duplication. By contrast, levels of some repressive modifications gradually increased during G2 and the next G1 phases. We applied this method to validate the target modifications of various histone demethylases in cells using a transient overexpression system. In extracts of marine organisms, we also screened chemical compounds that affect histone modifications and identified psammaplin A, which was previously reported to inhibit histone deacetylases. Thus, the method presented here is a powerful and convenient tool for analyzing the changes in histone modifications.

Resurgent Sodium Current in Neurons of the Cerebral Cortex

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.760610 ◽

2021 ◽

Vol 15 ◽

Author(s):

Giulia Quattrocolo ◽

Keagan Dunville ◽

Maximiliano José Nigro

Keyword(s):

Cerebral Cortex ◽

Current Knowledge ◽

Sodium Current ◽

Basic Research ◽

Cell Types ◽

Neuronal Types ◽

And Function ◽

Cerebellar Purkinje Neurons ◽

Different Cell Types ◽

Resurgent Sodium Current

In the late ’90, Dr. Indira Raman, at the time a postdoctoral fellow with Dr. Bruce Bean, at Harvard University, identified a new type of sodium current, flowing through the channels that reopens when the membrane is repolarized. This current, called “resurgent Sodium current,” was originally identified in cerebellar Purkinje neurons and has now been confirmed in around 20 different neuronal types. Since moving to Northwestern University in 1999 to establish her own research group, Dr. Raman has dedicated great efforts in identifying the mechanisms supporting the resurgent Sodium current and how its biophysical properties shape the firing of the different cell types. Her work has impacted greatly the field of cellular neurophysiology, from basic research to translation neuroscience. In fact, alterations in the resurgent sodium currents have been observed in several neuropathologies, from Huntington’s disease to epilepsy. In this Perspective we will focus on the current knowledge on the expression and function of the resurgent Sodium current in neurons of the cerebral cortex and hippocampus. We will also briefly highlight the role of Dr. Raman’s as teacher and mentor, not only for her pupils, but for the whole scientific community.

UNBIASED STEREOLOGICAL ESTIMATION OF DIFFERENT CELL TYPES IN RAT CEREBRAL CORTEX

Image Analysis & Stereology ◽

10.5566/ias.v23.p1-11 ◽

2011 ◽

Vol 23 (1) ◽

pp. 1 ◽

Cited By ~ 12

Author(s):

Maziar Davanlou ◽

Donald F Smith

Keyword(s):

Endothelial Cells ◽

Cerebral Cortex ◽

Glial Cells ◽

Cell Types ◽

Rat Cerebral Cortex ◽

Systematic Sampling ◽

Numerical Density ◽

Light Microscopic Level ◽

The Mean ◽

The total numbers of neurons, glial cells, and endothelial cells in rat cerebral cortex were estimated using unbiased stereological counting techniques and systematic sampling. The reference volume chosen was the entire neocortex, most of the allocortex and parts of claustrum using the rhinal fissure as the macroscopical anatomical landmark. These regions are referred to collectively as syncortex. A method has been devised for reducing problems associated with the uncertainties that arise when distinguishing between various types of cells. At the light microscopic level, using the detailed criteria described in this article, the total numbers of neurons, glial cells, and endothelial cells, respectively, were estimated for the entire syncortex as the product of the estimate of the volume of the syncortex, made with point counting techniques, and the estimates of the numerical density for each group of cells, made with optical disectors. In a sample of three brains, the mean total number of cells (neurons, glial and endothelial) in the syncortex of the rat brain is 128 x 106. This number is made up of 47% neurons, 24% glial cells, 17% endothelial cells, and 11% uncertain cell types (probably mostly glial cells).

A connectomic study of a petascale fragment of human cerebral cortex

10.1101/2021.05.29.446289 ◽

2021 ◽

Author(s):

Alexander Shapson-Coe ◽

Michal Januszewski ◽

Daniel R Berger ◽

Art Pope ◽

Yuelong Wu ◽

...

Keyword(s):

Cerebral Cortex ◽

High Speed ◽

Pyramidal Neurons ◽

Three Dimensional ◽

Cell Types ◽

Dimensional Structure ◽

Inhibitory Synapses ◽

Excitatory Synapses ◽

Split And Merge ◽

Surgical Sample

We acquired a rapidly preserved human surgical sample from the temporal lobe of the cerebral cortex. We stained a 1 mm3 volume with heavy metals, embedded it in resin, cut more than 5000 slices at ~30 nm and imaged these sections using a high-speed multibeam scanning electron microscope. We used computational methods to render the three-dimensional structure of 50,000 cells, hundreds of millions of neurites and 130 million synaptic connections. The 1.3 petabyte electron microscopy volume, the segmented cells, cell parts, blood vessels, myelin, inhibitory and excitatory synapses, and 100 manually proofread cells are available to peruse online. Despite the incompleteness of the automated segmentation caused by split and merge errors, many interesting features were evident. Glia outnumbered neurons 2:1 and oligodendrocytes were the most common cell type in the volume. The E:I balance of neurons was 69:31%, as was the ratio of excitatory versus inhibitory synapses in the volume. The E:I ratio of synapses was significantly higher on pyramidal neurons than inhibitory interneurons. We found that deep layer excitatory cell types can be classified into subsets based on structural and connectivity differences, that chandelier interneurons not only innervate excitatory neuron initial segments as previously described, but also each others initial segments, and that among the thousands of weak connections established on each neuron, there exist rarer highly powerful axonal inputs that establish multi-synaptic contacts (up to ~20 synapses) with target neurons. Our analysis indicates that these strong inputs are specific, and allow small numbers of axons to have an outsized role in the activity of some of their postsynaptic partners.

A network model of the modulation of gamma oscillations by NMDA receptors in cerebral cortex

10.1101/2021.12.21.473671 ◽

2021 ◽

Author(s):

Eduarda Susin ◽

Alain Destexhe

Keyword(s):

Cerebral Cortex ◽

Nmda Receptors ◽

Computational Models ◽

Gamma Oscillations ◽

Inhibitory Interneurons ◽

Nmda Receptor Antagonists ◽

Nmda Antagonists ◽

Gamma Power ◽

Underlying Mechanisms ◽

Psychotic drugs such as ketamine induce symptoms close to schizophrenia, and stimulates the production of gamma oscillations, as also seen in patients, but the underlying mechanisms are still unclear. Here, we have used computational models of cortical networks generating gamma oscillations, and have integrated the action of drugs such as ketamine to partially block n-methyl-d-Aspartate (NMDA) receptors. The model can reproduce the modulation of gamma oscillations by NMDA-receptor antagonists, assuming that antagonists affect NMDA receptors predominantly on inhibitory interneurons. We next used the model to compare the responsiveness of the network to external stimuli, and found that when NMDA channnels are blocked an increase of Gamma power is observed altogether with an increase of network responsiveness. However, this responsiveness increase applies not only to gamma states, but also to synchronous states with no apparent gamma. We conclude that NMDA antagonists induce increased excitability state, which may or may not produce gamma oscillations, but the response to external inputs is exacerbated, which may explain phenomena such as altered perception or hallucinations.

Kinesin-6 KIF20B is required for efficient cytokinetic furrowing and timely abscission in human cells

10.1101/171900 ◽

2017 ◽

Author(s):

Kerstin M. Janisch ◽

Katrina C. McNeely ◽

Joseph M. Dardick ◽

Samuel H. Lim ◽

Noelle D. Dwyer

Keyword(s):

Stem Cells ◽

Cerebral Cortex ◽

Cell Types ◽

Human Cells ◽

The Other ◽

Central Spindle ◽

Temporal Regulation ◽

A Cell ◽

Late Maturation ◽

ABSTRACTCytokinesis requires the cooperation of many cytoskeletal and membrane regulators. Most of the major players required for cytokinesis are known, but the temporal regulation and adaptations for different cell types are less understood. KIF20B (previously called MPHOSPH1 or MPP1) is a member of the Kinesin-6 family, which also includes the better-known members KIF23/MKLP1 and KIF20A/MKLP2. Previously, we showed that mouse Kif20b is involved in cerebral cortex growth and midbody organization of neural stem cells. Here we show that KIF20B has a cell-autonomous role in cytokinesis in isolated human cells. It localizes to microtubules of the central spindle and midbody throughout cytokinesis, at sites distinct from the other Kinesin-6 family members. KIF20B is not required for central spindle or midbody assembly, but affects midbody shape and late maturation steps. KIF20B appears to temporally regulate both furrow ingression and abscission.

Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053310 ◽

1982 ◽

Vol 40 ◽

pp. 118-119

Author(s):

U. Aebi ◽

P. Rew ◽

T.-T. Sun

Keyword(s):

Electron Microscopy ◽

Structural Organization ◽

Cell Types ◽

Structural Features ◽

Molecular Architecture ◽

The Past ◽

Keratin Filaments ◽

Different Types ◽

10 Nm Filaments ◽

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.