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Article ; Online: Selection of stimulus parameters for enhancing slow wave sleep events with a neural-field theory thalamocortical model.

Felipe A Torres / Patricio Orio / María-José Escobar

PLoS Computational Biology, Vol 17, Iss 7, p e

2021 Volume 1008758

Abstract: Slow-wave sleep cortical brain activity, conformed by slow-oscillations and sleep spindles, plays a key role in memory consolidation. The increase of the power of the slow-wave events, obtained by auditory sensory stimulation, positively correlates with ... ...

Abstract	Slow-wave sleep cortical brain activity, conformed by slow-oscillations and sleep spindles, plays a key role in memory consolidation. The increase of the power of the slow-wave events, obtained by auditory sensory stimulation, positively correlates with memory consolidation performance. However, little is known about the experimental protocol maximizing this effect, which could be induced by the power of slow-oscillation, the number of sleep spindles, or the timing of both events' co-occurrence. Using a mean-field model of thalamocortical activity, we studied the effect of several stimulation protocols, varying the pulse shape, duration, amplitude, and frequency, as well as a target-phase using a closed-loop approach. We evaluated the effect of these parameters on slow-oscillations (SO) and sleep-spindles (SP), considering: (i) the power at the frequency bands of interest, (ii) the number of SO and SP, (iii) co-occurrences between SO and SP, and (iv) synchronization of SP with the up-peak of the SO. The first three targets are maximized using a decreasing ramp pulse with a pulse duration of 50 ms. Also, we observed a reduction in the number of SO when increasing the stimulus energy by rising its amplitude. To assess the target-phase parameter, we applied closed-loop stimulation at 0°, 45°, and 90° of the phase of the narrow-band filtered ongoing activity, at 0.85 Hz as central frequency. The 0° stimulation produces better results in the power and number of SO and SP than the rhythmic or random stimulation. On the other hand, stimulating at 45° or 90° change the timing distribution of spindles centers but with fewer co-occurrences than rhythmic and 0° phase. Finally, we propose the application of closed-loop stimulation at the rising zero-cross point using pulses with a decreasing ramp shape and 50 ms of duration for future experimental work.
Keywords	Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cholinergic neuromodulation of inhibitory interneurons facilitates functional integration in whole-brain models.

Carlos Coronel-Oliveros / Rodrigo Cofré / Patricio Orio

PLoS Computational Biology, Vol 17, Iss 2, p e

2021 Volume 1008737

Abstract: Segregation and integration are two fundamental principles of brain structural and functional organization. Neuroimaging studies have shown that the brain transits between different functionally segregated and integrated states, and neuromodulatory ... ...

Abstract	Segregation and integration are two fundamental principles of brain structural and functional organization. Neuroimaging studies have shown that the brain transits between different functionally segregated and integrated states, and neuromodulatory systems have been proposed as key to facilitate these transitions. Although whole-brain computational models have reproduced this neuromodulatory effect, the role of local inhibitory circuits and their cholinergic modulation has not been studied. In this article, we consider a Jansen & Rit whole-brain model in a network interconnected using a human connectome, and study the influence of the cholinergic and noradrenergic neuromodulatory systems on the segregation/integration balance. In our model, we introduce a local inhibitory feedback as a plausible biophysical mechanism that enables the integration of whole-brain activity, and that interacts with the other neuromodulatory influences to facilitate the transition between different functional segregation/integration regimes in the brain.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Extracting temporal relationships between weakly coupled peptidergic and motoneuronal signaling

Miguel Piñeiro / Wilson Mena / John Ewer / Patricio Orio

PLoS Computational Biology, Vol 17, Iss 12, p e

Application to Drosophila ecdysis behavior.

2021 Volume 1008933

Abstract: Neuromodulators, such as neuropeptides, can regulate and reconfigure neural circuits to alter their output, affecting in this way animal physiology and behavior. The interplay between the activity of neuronal circuits, their modulation by neuropeptides, ... ...

Abstract	Neuromodulators, such as neuropeptides, can regulate and reconfigure neural circuits to alter their output, affecting in this way animal physiology and behavior. The interplay between the activity of neuronal circuits, their modulation by neuropeptides, and the resulting behavior, is still poorly understood. Here, we present a quantitative framework to study the relationships between the temporal pattern of activity of peptidergic neurons and of motoneurons during Drosophila ecdysis behavior, a highly stereotyped motor sequence that is critical for insect growth. We analyzed, in the time and frequency domains, simultaneous intracellular calcium recordings of peptidergic CCAP (crustacean cardioactive peptide) neurons and motoneurons obtained from isolated central nervous systems throughout fictive ecdysis behavior induced ex vivo by Ecdysis triggering hormone. We found that the activity of both neuronal populations is tightly coupled in a cross-frequency manner, suggesting that CCAP neurons modulate the frequency of motoneuron firing. To explore this idea further, we used a probabilistic logistic model to show that calcium dynamics in CCAP neurons can predict the oscillation of motoneurons, both in a simple model and in a conductance-based model capable of simulating many features of the observed neural dynamics. Finally, we developed an algorithm to quantify the motor behavior observed in videos of pupal ecdysis, and compared their features to the patterns of neuronal calcium activity recorded ex vivo. We found that the motor activity of the intact animal is more regular than the motoneuronal activity recorded from ex vivo preparations during fictive ecdysis behavior; the analysis of the patterns of movement also allowed us to identify a new post-ecdysis phase.
Keywords	Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cortical ignition dynamics is tightly linked to the core organisation of the human connectome.

Samy Castro / Wael El-Deredy / Demian Battaglia / Patricio Orio

PLoS Computational Biology, Vol 16, Iss 7, p e

2020 Volume 1007686

Abstract: The capability of cortical regions to flexibly sustain an "ignited" state of activity has been discussed in relation to conscious perception or hierarchical information processing. Here, we investigate how the intrinsic propensity of different regions to ...

Abstract	The capability of cortical regions to flexibly sustain an "ignited" state of activity has been discussed in relation to conscious perception or hierarchical information processing. Here, we investigate how the intrinsic propensity of different regions to get ignited is determined by the specific topological organisation of the structural connectome. More specifically, we simulated the resting-state dynamics of mean-field whole-brain models and assessed how dynamic multistability and ignition differ between a reference model embedding a realistic human connectome, and alternative models based on a variety of randomised connectome ensembles. We found that the strength of global excitation needed to first trigger ignition in a subset of regions is substantially smaller for the model embedding the empirical human connectome. Furthermore, when increasing the strength of excitation, the propagation of ignition outside of this initial core-which is able to self-sustain its high activity-is way more gradual than for any of the randomised connectomes, allowing for graded control of the number of ignited regions. We explain both these assets in terms of the exceptional weighted core-shell organisation of the empirical connectome, speculating that this topology of human structural connectivity may be attuned to support enhanced ignition dynamics.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Negative Modulation of TRPM8 Channel Function by Protein Kinase C in Trigeminal Cold Thermoreceptor Neurons

Bastián Rivera / Matías Campos / Patricio Orio / Rodolfo Madrid / María Pertusa

International Journal of Molecular Sciences, Vol 21, Iss 4420, p

2020 Volume 4420

Abstract: TRPM8 is the main molecular entity responsible for cold sensing. This polymodal ion channel is activated by cold, cooling compounds such as menthol, voltage, and rises in osmolality. In corneal cold thermoreceptor neurons (CTNs), TRPM8 expression ... ...

Abstract	TRPM8 is the main molecular entity responsible for cold sensing. This polymodal ion channel is activated by cold, cooling compounds such as menthol, voltage, and rises in osmolality. In corneal cold thermoreceptor neurons (CTNs), TRPM8 expression determines not only their sensitivity to cold, but also their role as neural detectors of ocular surface wetness. Several reports suggest that Protein Kinase C (PKC) activation impacts on TRPM8 function; however, the molecular bases of this functional modulation are still poorly understood. We explored PKC-dependent regulation of TRPM8 using Phorbol 12-Myristate 13-Acetate to activate this kinase. Consistently, recombinant TRPM8 channels, cultured trigeminal neurons, and free nerve endings of corneal CTNs revealed a robust reduction of TRPM8-dependent responses under PKC activation. In corneal CTNs, PKC activation decreased ongoing activity, a key parameter in the role of TRPM8-expressing neurons as humidity detectors, and also the maximal cold-evoked response, which were validated by mathematical modeling. Biophysical analysis indicated that PKC-dependent downregulation of TRPM8 is mainly due to a decreased maximal conductance value, and complementary noise analysis revealed a reduced number of functional channels at the cell surface, providing important clues to understanding the molecular mechanisms of how PKC activity modulates TRPM8 channels in CTNs.
Keywords	primary sensory neurons ; corneal nerve endings ; cold transduction ; plasma membrane ; PMA ; menthol ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Synchronization transition in neuronal networks composed of chaotic or non-chaotic oscillators

Kesheng Xu / Jean Paul Maidana / Samy Castro / Patricio Orio

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 12

Abstract: Abstract Chaotic dynamics has been shown in the dynamics of neurons and neural networks, in experimental data and numerical simulations. Theoretical studies have proposed an underlying role of chaos in neural systems. Nevertheless, whether chaotic neural ...

Abstract	Abstract Chaotic dynamics has been shown in the dynamics of neurons and neural networks, in experimental data and numerical simulations. Theoretical studies have proposed an underlying role of chaos in neural systems. Nevertheless, whether chaotic neural oscillators make a significant contribution to network behaviour and whether the dynamical richness of neural networks is sensitive to the dynamics of isolated neurons, still remain open questions. We investigated synchronization transitions in heterogeneous neural networks of neurons connected by electrical coupling in a small world topology. The nodes in our model are oscillatory neurons that – when isolated – can exhibit either chaotic or non-chaotic behaviour, depending on conductance parameters. We found that the heterogeneity of firing rates and firing patterns make a greater contribution than chaos to the steepness of the synchronization transition curve. We also show that chaotic dynamics of the isolated neurons do not always make a visible difference in the transition to full synchrony. Moreover, macroscopic chaos is observed regardless of the dynamics nature of the neurons. However, performing a Functional Connectivity Dynamics analysis, we show that chaotic nodes can promote what is known as multi-stable behaviour, where the network dynamically switches between a number of different semi-synchronized, metastable states.
Keywords	Medicine ; R ; Science ; Q
Subject code	515 ; 612
Language	English
Publishing date	2018-05-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Simple, fast and accurate implementation of the diffusion approximation algorithm for stochastic ion channels with multiple states.

Patricio Orio / Daniel Soudry

PLoS ONE, Vol 7, Iss 5, p e

2012 Volume 36670

Abstract: BACKGROUND: The phenomena that emerge from the interaction of the stochastic opening and closing of ion channels (channel noise) with the non-linear neural dynamics are essential to our understanding of the operation of the nervous system. The effects ... ...

Abstract	BACKGROUND: The phenomena that emerge from the interaction of the stochastic opening and closing of ion channels (channel noise) with the non-linear neural dynamics are essential to our understanding of the operation of the nervous system. The effects that channel noise can have on neural dynamics are generally studied using numerical simulations of stochastic models. Algorithms based on discrete Markov Chains (MC) seem to be the most reliable and trustworthy, but even optimized algorithms come with a non-negligible computational cost. Diffusion Approximation (DA) methods use Stochastic Differential Equations (SDE) to approximate the behavior of a number of MCs, considerably speeding up simulation times. However, model comparisons have suggested that DA methods did not lead to the same results as in MC modeling in terms of channel noise statistics and effects on excitability. Recently, it was shown that the difference arose because MCs were modeled with coupled gating particles, while the DA was modeled using uncoupled gating particles. Implementations of DA with coupled particles, in the context of a specific kinetic scheme, yielded similar results to MC. However, it remained unclear how to generalize these implementations to different kinetic schemes, or whether they were faster than MC algorithms. Additionally, a steady state approximation was used for the stochastic terms, which, as we show here, can introduce significant inaccuracies. MAIN CONTRIBUTIONS: We derived the SDE explicitly for any given ion channel kinetic scheme. The resulting generic equations were surprisingly simple and interpretable--allowing an easy, transparent and efficient DA implementation, avoiding unnecessary approximations. The algorithm was tested in a voltage clamp simulation and in two different current clamp simulations, yielding the same results as MC modeling. Also, the simulation efficiency of this DA method demonstrated considerable superiority over MC methods, except when short time steps or low channel numbers were used.
Keywords	Medicine ; R ; Science ; Q
Subject code	518
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Quantitative analysis of cell migration using optical flow.

Katica Boric / Patricio Orio / Thierry Viéville / Kathleen Whitlock

PLoS ONE, Vol 8, Iss 7, p e

2013 Volume 69574

Abstract: Neural crest cells exhibit dramatic migration behaviors as they populate their distant targets. Using a line of zebrafish expressing green fluorescent protein (sox10:EGFP) in neural crest cells we developed an assay to analyze and quantify cell migration ...

Abstract	Neural crest cells exhibit dramatic migration behaviors as they populate their distant targets. Using a line of zebrafish expressing green fluorescent protein (sox10:EGFP) in neural crest cells we developed an assay to analyze and quantify cell migration as a population, and use it here to characterize in detail the subtle defects in cell migration caused by ethanol exposure during early development. The challenge was to quantify changes in the in vivo migration of all Sox10:EGFP expressing cells in the visual field of time-lapse movies. To perform this analysis we used an Optical Flow algorithm for motion detection and combined the analysis with a fit to an affine transformation. Through this analysis we detected and quantified significant differences in the cell migrations of Sox10:EGFP positive cranial neural crest populations in ethanol treated versus untreated embryos. Specifically, treatment affected migration by increasing the left-right asymmetry of the migrating cells and by altering the direction of cell movements. Thus, by applying this novel computational analysis, we were able to quantify the movements of populations of cells, allowing us to detect subtle changes in cell behaviors. Because cranial neural crest cells contribute to the formation of the frontal mass these subtle differences may underlie commonly observed facial asymmetries in normal human populations.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: TRPM8-Dependent Dynamic Response in a Mathematical Model of Cold Thermoreceptor.

Erick Olivares / Simón Salgado / Jean Paul Maidana / Gaspar Herrera / Matías Campos / Rodolfo Madrid / Patricio Orio

PLoS ONE, Vol 10, Iss 10, p e

2015 Volume 0139314

Abstract: Cold-sensitive nerve terminals (CSNTs) encode steady temperatures with regular, rhythmic temperature-dependent firing patterns that range from irregular tonic firing to regular bursting (static response). During abrupt temperature changes, CSNTs show a ... ...

Abstract	Cold-sensitive nerve terminals (CSNTs) encode steady temperatures with regular, rhythmic temperature-dependent firing patterns that range from irregular tonic firing to regular bursting (static response). During abrupt temperature changes, CSNTs show a dynamic response, transiently increasing their firing frequency as temperature decreases and silencing when the temperature increases (dynamic response). To date, mathematical models that simulate the static response are based on two depolarizing/repolarizing pairs of membrane ionic conductance (slow and fast kinetics). However, these models fail to reproduce the dynamic response of CSNTs to rapid changes in temperature and notoriously they lack a specific cold-activated conductance such as the TRPM8 channel. We developed a model that includes TRPM8 as a temperature-dependent conductance with a calcium-dependent desensitization. We show by computer simulations that it appropriately reproduces the dynamic response of CSNTs from mouse cornea, while preserving their static response behavior. In this model, the TRPM8 conductance is essential to display a dynamic response. In agreement with experimental results, TRPM8 is also needed for the ongoing activity in the absence of stimulus (i.e. neutral skin temperature). Free parameters of the model were adjusted by an evolutionary optimization algorithm, allowing us to find different solutions. We present a family of possible parameters that reproduce the behavior of CSNTs under different temperature protocols. The detection of temperature gradients is associated to a homeostatic mechanism supported by the calcium-dependent desensitization.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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