Análisis del efecto de la modulación de conductancias sub-umbrales sobre la excitabilidad de neuronas talamocorticales mediante el uso de dynamic clamp. / Effect of the modulation of subthreshold conductances on the excitability of talamocortical neurons.

Portillo, Javier Omar (2016) Análisis del efecto de la modulación de conductancias sub-umbrales sobre la excitabilidad de neuronas talamocorticales mediante el uso de dynamic clamp. / Effect of the modulation of subthreshold conductances on the excitability of talamocortical neurons. Master in Medical Physics, Universidad Nacional de Cuyo, Instituto Balseiro.

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Abstract in Spanish

El comportamiento oscilatorio de neuronas talamocorticales normalmente esta asociado al procesamiento sensorial y cognitivo. En casos patológicos, este tipo de comportamiento también puede estar asociado a, por ejemplo, distintos tipos de crisis epilépticas. Trabajos previos de nuestro laboratorio realizaron predicciones acerca de la influencia de distintas corrientes de bajo umbral sobre la propensión a oscilar de las neuronas talamocorticales. Se demostró que pequeños cambios en los parámetros que modelan distintas corrientes, podrían empujar al sistema oscilatorio talamocortical fuera del rango fisiológico y hacia el tipo de oscilaciones patológicas que se observan en estos tipos de epilepsia. Este trabajo tuvo como objetivo el estudio experimental de dichas predicciones. Para ello realizamos experimentos en neuronas talamocorticales de ratón. En particular demostramos la importancia de la corriente rectificadora de entrada de potasio I_Kir y la corriente de bajo umbral de calcio I_T en la generación de disparos en ráfaga, que es el modo de disparo asociado a sueño NREM y también a episodios de epilepsia de ausencia. Además se exploro el papel de las conductancias subumbrales sobre la modulación de la ganancia de estas neuronas. Encontramos que los parámetros de voltaje-dependencia de la corriente de potasio I_A son determinantes para esta modulación.

Abstract in English

The oscillatory behavior of thalamocortical neurons is usually linked to sensory and cognitive processing. This cellular behavior is also associated to pathological states such as epileptic seizures. Several predictions about the influence of different subthreshold ionic currents on the propensity of thalamocortical neurons to oscillate were made in previous studies carried out in our laboratory. It was shown that oscillations similar to those seen in these types of epilepsy can be induced in a computational model of a thalamocortical neuron after small changes in single parameters of several subtrheshold conductances. The main objective of this thesis work was to investigate experimentally those predictions. For that, we perform in vitro experiments on thalamocortical neurons from mice. We were able to show the importance of the inward rectifier potassium current I_Kir and the low threshold calcium current I_T on the generation of repetitive burst firing: a mode of firing characteristic of absence epilepsy. In addition, we explored the role of the subthrehold conductances on the gain modulation of the input/ouput transformation of thalamocortical neurons. We found that the voltage-dependence of the transient potassium current I_A are determinants of this modulation.

Item Type:Thesis (Master in Medical Physics)
Keywords:Nerve cells; Celulas nerviosas; Epilepsy; Epilepsia; [Neurons; Neuronas; Thalamocortical neurons; Neuronas talamocorticales; Dynamic clamp ]
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Subjects:Medicine > Neurosciences
Divisions:Gcia. de área de Investigación y aplicaciones no nucleares > Gcia. de Física > Sistemas complejos y altas energías > Física estadística interdisciplinaria
ID Code:575
Deposited By:Tamara Cárcamo
Deposited On:21 Apr 2017 18:11
Last Modified:21 Apr 2017 18:11

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