Electroencephalography (EEG) has become very common in clinical practice due to its relatively low cost, ease of installation, non-invasiveness, and good temporal resolution. Portable EEG devices are ...increasingly popular in clinical monitoring applications such as sleep scoring or anesthesia monitoring. In these situations, for reasons of speed and simplicity only few electrodes are used and contamination of the EEG signal by artifacts is inevitable. Visual inspection and manual removal of artifacts is often not possible, especially in real-time applications. Our goal is to develop a flexible technique to remove EEG artifacts in these contexts with minimal supervision. We propose here a new wavelet-based method which allows to remove artifacts from single-channel EEGs. The method is based on a data-driven renormalization of the wavelet components and is capable of adaptively attenuate artifacts of different nature. We benchmark our method against alternative artifact removal techniques. We assessed the performance of the proposed method on publicly available datasets comprising ocular, muscular, and movement artifacts. The proposed method shows superior performances on different kinds of artifacts and signal-to-noise levels. Finally, we present an application of our method to the monitoring of general anesthesia. We show that our method can successfully attenuate various types of artifacts in single-channel EEG. Thanks to its data-driven approach and low computational cost, the proposed method provides a valuable tool to remove artifacts in real-time EEG applications with few electrodes, such as monitoring in special care units.
Phase separated domains (PSDs) are ubiquitous in cell biology, representing nanoregions of high molecular concentration. PSDs appear at diverse cellular domains, such as neuronal synapses but also in ...eukaryotic cell nucleus, limiting the access of transcription factors and thus preventing gene expression. We develop a generalized cross-linker polymer model, to study PSDs: we show that increasing the number of cross-linkers induces a polymer condensation, preventing access of diffusing molecules. To investigate how the PSDs restrict the motion of diffusing molecules, we compute the mean residence and first escaping times. Finally, we develop a method based on mean-square-displacement of single particle trajectories to reconstruct the properties of PSDs from the continuum range of anomalous exponents. We also show here that PSD generated by polymers do not induces a long-range attracting field (potential well), in contrast with nanodomains at neuronal synapses. To conclude, PSDs can result from condensed chromatin organization, where the number of cross-linkers controls molecular access.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rhythmic neuronal network activity underlies brain oscillations. To investigate how connected neuronal networks contribute to the emergence of the α-band and to the regulation of Up and Down states, ...we study a model based on synaptic short-term depression-facilitation with afterhyperpolarization (AHP). We found that the α-band is generated by the network behavior near the attractor of the Up-state. Coupling inhibitory and excitatory networks by reciprocal connections leads to the emergence of a stable α-band during the Up states, as reflected in the spectrogram. To better characterize the emergence and stability of thalamocortical oscillations containing α and δ rhythms during anesthesia, we model the interaction of two excitatory networks with one inhibitory network, showing that this minimal topology underlies the generation of a persistent α-band in the neuronal voltage characterized by dominant Up over Down states. Finally, we show that the emergence of the α-band appears when external inputs are suppressed, while fragmentation occurs at small synaptic noise or with increasing inhibitory inputs. To conclude, α-oscillations could result from the synaptic dynamics of interacting excitatory neuronal networks with and without AHP, a principle that could apply to other rhythms.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dynamic aspects of interactions between astrocytes, neurons and the vasculature have recently been in the neuroscience spotlight. It has emerged that not only neurons but also astrocytes are ...organized into networks. Whereas neuronal networks exchange information through electrical and chemical synapses, astrocytes are interconnected through gap junction channels that are regulated by extra- and intracellular signals and allow exchange of information. This intercellular communication between glia has implications for neuroglial and gliovascular interactions and hence has added another level of complexity to our understanding of brain function.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Most synaptic excitatory connections are made on dendritic spines. But how the voltage in spines is modulated by its geometry remains unclear. To investigate the electrical properties of spines, we ...combine voltage imaging data with electro-diffusion modeling. We first present a temporal deconvolution procedure for the genetically encoded voltage sensor expressed in hippocampal cultured neurons and then use electro-diffusion theory to compute the electric field and the current-voltage conversion. We extract a range for the neck resistances of 〈R〉=100±35MΩ. When a significant current is injected in a spine, the neck resistance can be inversely proportional to its radius, but not to the radius square, as predicted by Ohm’s law. We conclude that the postsynaptic voltage cannot only be modulated by changing the number of receptors, but also by the spine geometry. Thus, spine morphology could be a key component in determining synaptic transduction and plasticity.
•Deconvolution of fluorescence Arclight to recover voltage in dendritic spines•The voltage distribution in spines modulated by geometry and electro-diffusion•A concentration gradient appears in the spine neck following a synaptic input•Spine electrical resistance depends on the injected current, Ohm’s law not valid
Based on fluorescence recordings, Cartailler et al. recover the voltage dynamics in dendritic spines by deconvolution. They investigate electricity at a nanometric scale using electro-diffusion modeling and concluded that spine geometry and electrolyte shape the current-voltage conversion and electrical resistance.
Chromatin organization can be probed by Chromosomal Capture (5C) data, from which the encounter probability (EP) between genomic sites is presented in a large matrix. This matrix is averaged over a ...large cell population, revealing diagonal blocks called Topological Associating Domains (TADs) that represent a sub-chromatin organization. To study the relation between chromatin organization and gene regulation, we introduce a computational procedure to construct a bead-spring polymer model based on the EP matrix. The model permits exploring transient properties constrained by the statistics of the 5C data. To construct the polymer model, we proceed in two steps: first, we introduce a minimal number of random connectors inside restricted regions to account for diagonal blocks. Second, we account for long-range frequent specific genomic interactions. Using the constructed polymer, we compute the first encounter time distribution and the conditional probability of three key genomic sites. By simulating single particle trajectories of loci located on the constructed polymers from 5C data, we found a large variability of the anomalous exponent, used to interpret live cell imaging trajectories. The present polymer construction provides a generic tool to study steady-state and transient properties of chromatin constrained by some physical properties embedded in 5C data.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fast calcium transients (<10 ms) remain difficult to analyse in cellular microdomains, yet they can modulate key cellular events such as trafficking, local ATP production by endoplasmic ...reticulum-mitochondria complex (ER-mitochondria complex), or spontaneous activity in astrocytes. In dendritic spines receiving synaptic inputs, we show here that in the presence of a spine apparatus (SA), which is an extension of the smooth ER, a calcium-induced calcium release (CICR) is triggered at the base of the spine by the fastest calcium ions arriving at a Ryanodyne receptor (RyR). The mechanism relies on the asymmetric distributions of RyRs and sarco/ER calcium-ATPase (SERCA) pumps that we predict using a computational model and further confirm experimentally in culture and slice hippocampal neurons. The present mechanism for which the statistics of the fastest particles arriving at a small target, followed by an amplification, is likely to be generic in molecular transduction across cellular microcompartments, such as thin neuronal processes, astrocytes, endfeets, or protrusions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The cerebral cortex is continuously active in the absence of external stimuli. An example of this spontaneous activity is the voltage transition between an Up and a Down state, observed ...simultaneously at individual neurons. Since this phenomenon could be of critical importance for working memory and attention, its explanation could reveal some fundamental properties of cortical organization. To identify a possible scenario for the dynamics of Up-Down states, we analyze a reduced stochastic dynamical system that models an interconnected network of excitatory neurons with activity-dependent synaptic depression. The model reveals that when the total synaptic connection strength exceeds a certain threshold, the phase space of the dynamical system contains two attractors, interpreted as Up and Down states. In that case, synaptic noise causes transitions between the states. Moreover, an external stimulation producing a depolarization increases the time spent in the Up state, as observed experimentally. We therefore propose that the existence of Up-Down states is a fundamental and inherent property of a noisy neural ensemble with sufficiently strong synaptic connections.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
While neuronal mitochondria have been studied extensively in their role in health and disease, the rules that govern calcium regulation in mitochondria remain somewhat vague. In the present study ...using cultured rat hippocampal neurons transfected with the mtRCaMP mitochondrial calcium sensor, we investigated the effects of cytosolic calcium surges on the dynamics of mitochondrial calcium (Ca2+m). Cytosolic calcium (Ca2+c) was measured using the high affinity sensor Fluo-2. We recorded two types of calcium events: local and global ones. Local events were limited to a small, 2–5 µm section of the dendrite, presumably caused by local synaptic activity, while global events were associated with network bursts and extended throughout the imaged dendrite. In both cases, cytosolic surges were followed by a delayed rise in Ca2+m. In global events, the rise lasted longer and was observed in all mitochondrial clusters. At the end of the descending part of the global event, Ca2+m was still high. Global events were accompanied by short and rather high Ca2+m surges which we called spikelets, and were present until the complete decay of the cytosolic event. In the case of local events, selective short-term responses were limited to the part of the mitochondrial cluster that was located directly in the center of Ca2+c activity, and faded quickly, while responses in the neighboring regions were rarely observed. Caffeine (which recruits ryanodine receptors to supply calcium to the mitochondria), and carbonyl cyanide m-chlorophenyl hydrazine (CCCP, a mitochondrial uncoupler) could affect Ca2+m in both global and local events. We constructed a computational model to simulate the fundamental role of mitochondria in restricting calcium signals within a narrow range under synapses, preventing diffusion into adjacent regions of the dendrite. Our results indicate that local cytoplasmic and mitochondrial calcium concentrations are highly correlated. This reflects a key role of signaling pathways that connect the postsynaptic membrane to local mitochondrial clusters.
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