Repositorio UV :: Examinando por Autor "Orio, Patricio"

Examinando por Autor "Orio, Patricio"

Mostrando 1 - 10 de 10

Cholinergic neuromodulation of inhibitory interneurons facilitates functional integration in whole-brain models
(Plos, 2021) Coronel-Oliveros, Carlos; Cofré, Rodrigo; Orio, Patricio
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.
Constitutive Phosphorylation as a Key Regulator of TRPM8 Channel Function
(Society For Neuroscience, 2021) Rivera, Bastián; Moreno, Claudio; Lavanderos, Boris; Hwang, Ji Yeon; Fernández-Trillo, Jorge; Park, Kang-Sik; Orio, Patricio; Viana, Félix; Madrid, Rodolfo; Pertusa, María
In mammals, environmental cold sensing conducted by peripheral cold thermoreceptor neurons mostly depends on TRPM8, an ion channel that has evolved to become the main molecular cold transducer. This TRP channel is activated by cold, cooling compounds, such as menthol, voltage, and rises in osmolality. TRPM8 function is regulated by kinase activity that phosphorylates the channel under resting conditions. However, which specific residues, how this post-translational modification modulates TRPM8 activity, and its influence on cold sensing are still poorly understood. By mass spectrometry, we identified four serine residues within the N-terminus (S26, S29, S541, and S542) constitutively phosphorylated in the mouse ortholog. TRPM8 function was examined by Ca2+ imaging and patch-clamp recordings, revealing that treatment with staurosporine, a kinase inhibitor, augmented its cold- and menthol-evoked responses. S29A mutation is sufficient to increase TRPM8 activity, suggesting that phosphorylation of this residue is a central molecular determinant of this negative regulation. Biophysical and total internal reflection fluorescence-based analysis revealed a dual mechanism in the potentiated responses of unphosphorylated TRPM8: a shift in the voltage activation curve toward more negative potentials and an increase in the number of active channels at the plasma membrane. Importantly, basal kinase activity negatively modulates TRPM8 function at cold thermoreceptors from male and female mice, an observation accounted for by mathematical modeling. Overall, our findings suggest that cold temperature detection could be rapidly and reversibly fine-tuned by controlling the TRPM8 basal phosphorylation state, a mechanism that acts as a dynamic molecular brake of this thermo-TRP channel function in primary sensory neurons.
Diversity of neuronal activity is provided by hybrid synapses
(Springer, 2021) Xu, Kesheng; Maidana, Jean Paul; Orio, Patricio
The coexistence of electrical and chemical synaptic communication among excitatory cells has been evidenced by neuroscientists. Nevertheless, theoretical understanding of hybrid synaptic connections in diverse dynamical states of neural networks for self-organization and robustness, still has not been fully studied. Here, we present a model of neural network that includes chemical excitatory coupling in a way of small-world topology and electrical synaptic coupling among adjacent excitatory cells for excitatory population. Firstly, we use this model to investigate the effect of electrical synaptic coupling among excitatory cells on global network behavior with the goal of theoretically understanding mechanisms of generating rich firing patterns. Secondly, we further study the emergence of various firing ripple events by considering the variation of chemical synaptic inhibition and other factors, such as network densities. We found that the excitatory population has a tendency to synchronization as the weights of electrical synaptic coupling among excitatory cells are increased. Moreover, the existence of these electrical synaptic connections can cause various firing patterns of interest by slightly changing the chemical synaptic weights. Our results pave a way in the study of the dynamical mechanisms and computational significance of the contribution of mixed synapse in the neural functions.
Extracting temporal relationships between weakly coupled peptidergic and motoneuronal signaling: Application to Drosophila ecdysis behavior
(Plos, 2021) Piñeiro, Miguel; Mena, Wilson; Ewer, John; Orio, Patricio
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.
Mathematical Modeling in Neuroscience
(Springer, 2021) Orio, Patricio
Relación entre conectividad estructural y la estadística multivariada en modelos de redes neuronales
(Universidad de Valparaíso, 2022) Orellana Villota, Sebastián; Orio, Patricio
La cantidad y calidad de datos de conectividad estructural (SC) y funcional (FC) en humanos que están disponibles para la investigación ha aumentado enormemente en los últimos años, esto debido a iniciativas de consorcios internacionales de investigación e innovaciones tecnológicas en las últimas décadas. La relación entre ambas dimensiones –estructural y funcional– no está del todo clara y su comprensión tiene enorme potencial a nivel clínico; la comparación entre topologías de redes SC y FC entre sujetos de estudio ha revelado diferencias significativas entre pacientes con desórdenes neurológicos y psiquiátricos y pacientes sanos [1–4]. Tanto la SC como la FC se han estudiado tradicionalmente considerando exclusivamente relaciones de a pares, sin embargo diversos estudios sugieren que son las interacciones de alto orden (e.g., entre 3 o más elementos) las responsables de la emergencia de propiedades determinantes de la función cerebral [5][6]. Por un lado, el análisis de redes complejas permite cuantificar aspectos topológicos de las redes estructurales [7] mediante medidas neurobiológicamente significativas y relativamente sencillas de calcular [8]. Por otro lado, la teoría de la información multivariada entrega herramientas para el estudio de propiedades que emergen de las interacciones de alto orden (es decir, considerando simultáneamente tres o mas regiones cerebrales) como la redundancia y la sinergia estadística, esta ultima de gran interés, ya que es asociada con el procesamiento de información en redes prefrontal-parietal del cerebro y tareas cognitivas de alto nivel [9]. En la presente investigación de tesis se estudió la relación entre las propiedades topológicas de dos conjuntos de redes de SC (modular y de pequeño mundo), caracterizando sus niveles de integración y segregación estructural, y como estas dan forma a la estadística multivariada simulada sobre dichas topologías, determinando si la naturaleza de su régimen estadístico corresponde al tipo mayormente redundante o sinérgico. Los resultados obtenidos indican un aumento en la cantidad de interacciones sinérgicas en aquellas redes que poseen un balance entre integración y segregación estructural.
Relación entre conectividad estructural y la estadística multivariada en modelos de redes neuronales
(Universidad de Valparaíso, 2022) Orellana Villota, Sebastián; Orio, Patricio
La cantidad y calidad de datos de conectividad estructural (SC) y funcional (FC) en humanos que están disponibles para la investigación ha aumentado enormemente en los últimos años, esto debido a iniciativas de consorcios internacionales de investigación e innovaciones tecnológicas en las ultimas décadas. La relación entre ambas dimensiones –estructural y funcional– no está del todo clara y su comprensión tiene enorme potencial a nivel clínico; la comparación entre topologías de redes SC y FC entre sujetos de estudio ha revelado diferencias significativas entre pacientes con desordenes neurológicos y psiquiátricos y pacientes sanos [1–4]. Tanto la SC como la FC se han estudiado tradicionalmente considerando exclusivamente relaciones de a pares, sin embargo diversos estudios sugieren que son las interacciones de alto orden (e.g., entre 3 o más elementos) las responsables de la emergencia de propiedades determinantes de la función cerebral [5][6]. Por un lado, el análisis de redes complejas permite cuantificar aspectos topológicos de las redes estructurales [7] mediante medidas neurobiológicamente significativas y relativamente sencillas de calcular [8]. Por otro lado, la teoría de la información multivariada entrega herramientas para el estudio de propiedades que emergen de las interacciones de alto orden (es decir, considerando simultáneamente tres o mas regiones cerebrales) como la redundancia y la sinergia estadística, esta ultima de gran interés, ya que es asociada con el procesamiento de información en redes prefrontal-parietal del cerebro y tareas cognitivas de alto nivel [9]. En la presente investigación de tesis se estudió la relación entre las propiedades topológicas de dos conjuntos de redes de SC (modular y de pequeño mundo), caracterizando sus niveles de integración y segregación estructural, y como estas dan forma a la estadística multivariada simulada sobre dichas topologías, determinando si la naturaleza de su régimen estadístico corresponde al tipo mayormente redundante o sinérgico. Los resultados obtenidos indican un aumento en la cantidad de interacciones sinérgicas en aquellas redes que poseen un balance entre integración y segregación estructural.
Selection of stimulus parameters for enhancing slow wave sleep events with a neural-field theory thalamocortical model
(Plos, 2021) Torres, Felipe A.; Orio, Patricio; Escobar, María-José
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 sleepspindles (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.
Structural Features of the Human Connectome That Facilitate the Switching of Brain Dynamics via Noradrenergic Neuromodulation
(Frontiers, 2021) Coronel-Oliveros, Carlos; Castro, Samy; Cofré, Rodrigo; Orio, Patricio
The structural connectivity of human brain allows the coexistence of segregated and integrated states of activity. Neuromodulatory systems facilitate the transition between these functional states and recent computational studies have shown how an interplay between the noradrenergic and cholinergic systems define these transitions. However, there is still much to be known about the interaction between the structural connectivity and the effect of neuromodulation, and to what extent the connectome facilitates dynamic transitions. In this work, we use a whole brain model, based on the Jasen and Rit equations plus a human structural connectivity matrix, to find out which structural features of the human connectome network define the optimal neuromodulatory effects. We simulated the effect of the noradrenergic system as changes in filter gain, and studied its effects related to the global-, local-, and meso-scale features of the connectome. At the global-scale, we found that the ability of the network of transiting through a variety of dynamical states is disrupted by randomization of the connection weights. By simulating neuromodulation of partial subsets of nodes, we found that transitions between integrated and segregated states are more easily achieved when targeting nodes with greater connection strengths—local feature—or belonging to the rich club—meso-scale feature. Overall, our findings clarify how the network spatial features, at different levels, interact with neuromodulation to facilitate the switching between segregated and integrated brain states and to sustain a richer brain dynamics.
The neuromodulatory influence on functional network topolopy: insights from neural mass models
(Universidad de Valparaíso, 2022) Coronel Oliveros, Carlos; Orio, Patricio
En años recientes, los modelos de cerebro completo, informados con datos de neuroimagen, han sido utilizados para hallar mecanismos que permitan explicar el cómo y el porqué de la estructura y dinámica del cerebro. A partir de un conectoma fijo, el cerebro puede manejar la transición entre diferentes patrones de actividad funcional en escalas de tiempo relativamente cortas. Los sistemas neuromodulatorios constituyen un mecanismo plausible para cambiar el f lujo de la información dentro del cerebro, remoldeando conexiones funcionales en respuesta a un cambio en el contexto ambiental. Teorías recientes proponen que los sistemas colinérgico y noradrenérgico promueven topologías de red funcionales más segregadas o integradas, respectivamente. A pesar de que los efectos de la acetilcolina y la noradrenalina han sido estudiados extensivamente en humanos usando registros de actividad cerebral no invasivos, el vínculo causal entre los mecanismos biofísicos–atribuidos a los neuromodulares– y el control de la topología de red funcional no es conocido. En esta tesis, utilicé un modelo de cerebro completo de masas neuronales para ganar conocimiento acerca de los mecanismos específicos, relacionados con los sistemas colinérgico y noradrenérgico, que producen un movimiento hacia la segregación o integración funcional. En la primera parte, el muy conocido modelo de Jansen & Rit se utilizó para caracterizar el efecto de la acetilcolina y la noradrenalina sobre la segregación e integración. Herramientas de la teoría de grafos se emplearon para analizar las redes funcional obtenidas con las señales tipo fMRI BOLD simuladas. Mecanísticamente, la neuromodulación colinérgica se modeló disminuyendo los parámetros de acoplamiento global y de inhibición local del modelo. La influencia noradrenérgica se simuló incrementando la pendiente de la función de entrada-salida (llamada ganancia de filtro o neural) de las neuronas piramidales. Los resultados de las simulaciones confirman el efecto pro-segregación (integración) de la acetilcolina (noradrenalina), estableciendo mecanismos biofísicos robustos para simular el impacto de los neuromodudolares en la dinámica a nivel de cerebro completo. Luego, corroboré los resultados del modelo añadiendo el análisis de datos empíricos, encontrando que los efectos del sistema colinérgico son contexto específicos: este promueve la segregación durante una tarea atencional, pero no en condiciones de actividad espontánea. Finalmente, identifiqué algunas regiones claves en el conectoma de humano que, al ser neuromoduladas por noradrenalina, producen un mayor incremento en la integración funcional. Estas regiones corresponden a los hubs estructurales del cerebro, los cuales son piezas claves para facilitar la integración de la actividad cerebral.

Examinando por Autor "Orio, Patricio"

Resultados por página

Opciones de ordenación