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. Maestría en Física Médica, Universidad Nacional de Cuyo, Instituto Balseiro.

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Resumen en español

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.

Resumen en inglés

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.

Tipo de objeto:Tesis (Maestría en Física Médica)
Palabras Clave:Nerve cells; Celulas nerviosas; Epilepsy; Epilepsia; [Neurons; Neuronas; Thalamocortical neurons; Neuronas talamocorticales; Dynamic clamp ]
Referencias:[1] Evolution: How yeast go multicellular. Nature, 517 (7536), 531-531, jan 2015. URL http://dx.doi.org/10.1038/517531d. 1 [2] Schwartz, W. Helena curtis, biology. XVII und 862 s., 582 abb., 18 tab. new york 1969: Worth publ. inc. Z Allg Mikrobiol, 11 (4), 361-361, 1971. URL http: //dx.doi.org/10.1002/jobm.19710110417. 1 [3] Meinertzhagen, I. A., Okamura, Y. The larval ascidian nervous system: the chordate brain from its small beginnings. Trends Neurosci., 24 (7), 401-410, Jul 2001. 1 [4] Brown, A. G. FROM NEURON TO BRAIN: A CELLULAR APPROACH TO THE FUNCTION OF THE NERVOUS SYSTEM. by stephen w. kuer and john g. nicholls. Exp Physiol, 62 (3), 287{287, jul 1977. URL http://dx.doi.org/10. 1113/expphysiol.1977.sp002400. 2, 6, 17, 18 [5] Izhikevich, E. Simple model of spiking neurons. IEEE Trans. Neural Netw., 14 (6), 1569-1572, nov 2003. URL http://dx.doi.org/10.1109/TNN.2003.820440. 4, 18 [6] Fisher, M. Lehninger principles of biochemistry, 3rd edition by david l. nelson and michael m. cox. Chem. Educator, 6 (1), 69-70, feb 2001. URL http://dx.doi. org/10.1007/s00897000455a. 5 [7] Hodgkin AL, H. A. A quantitative description of membrane current and its application to conduction and excitation in nerve. The Journal of Physiology, 117 (4), 500{544, 1952. 9 [8] Kullmann, D. M. Neurological channelopathies. Annu. Rev. Neurosci., 33 (1), 151-172, jun 2010. URL http://dx.doi.org/10.1146/ annurev-neuro-060909-153122. 16 [9] Bal, T., Destexhe, A. (eds.) Dynamic-Clamp. Springer Science + Business Media, 2009. URL http://dx.doi.org/10.1007/978-0-387-89279-5. 20 [10] Tononi, G., Koch, C. Consciousness: here, there and everywhere? Philosophical Transactions of the Royal Society B: Biological Sciences, 370 (1668), 20140167- 20140167, mar 2015. URL http://dx.doi.org/10.1098/rstb.2014.0167. 23 [11] Ward, L. M. The thalamic dynamic core theory of conscious experience. Consciousness and Cognition, 20 (2), 464-486, jun 2011. URL http://dx.doi.org/ 10.1016/j.concog.2011.01.007. 23 [12] Sherman, S. M., Guillery, R. W. The role of the thalamus in the ow of information to the cortex. Philosophical Transactions of the Royal Society B: Biological Sciences, 357 (1428), 1695-1708, dec 2002. URL http://dx.doi.org/10.1098/ rstb.2002.1161. 23 [13] Buzsaki, G. Rhythms of the Brain. Oxford University Press (OUP), 2006. URL http://dx.doi.org/10.1093/acprof:oso/9780195301069.001.0001. 23, 24 [14] McCormick, D. A., Bal, T. SLEEP AND AROUSAL: Thalamocortical mechanisms. Annu. Rev. Neurosci., 20 (1), 185-215, mar 1997. URL http: //dx.doi.org/10.1146/annurev.neuro.20.1.185. 23 [15] T., B. Thalamic burst mode and inattention in the awake lgnd. Annu. Rev. Neurosci., 20 (1), 185-215, Feb 2006. 24, 58 [16] Amarillo, Y., Zagha, E., Mato, G., Rudy, B., Nadal, M. S. The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons. Journal of Neurophysiology, 112 (2), 393-410, apr 2014. URL http://dx.doi.org/10.1152/jn.00647.2013. 24, 25, 37, 39, 46, 47 [17] Huguenard, J. R., McCormick, D. A. Thalamic synchrony and dynamic regulation of global forebrain oscillations. Trends in Neurosciences, 30 (7), 350-356, jul 2007. URL http://dx.doi.org/10.1016/j.tins.2007.05.007. 24 [18] Llinas, R., Pare, D. Of dreaming and wakefulness. Neuroscience, 44 (3), 521-535, jan 1991. URL http://dx.doi.org/10.1016/0306-4522(91)90075-Y. 24 [19] McAlonan, K., Brown, V. J. The thalamic reticular nucleus: more than a sensory nucleus? Neuroscientist, 8 (4), 302-305, Aug 2002. 24 [20] Masterton, R. A., Carney, P. W., Jackson, G. D. Cortical and thalamic restingstate functional connectivity is altered in childhood absence epilepsy. Epilepsy Research, 99 (3), 327-334, may 2012. URL http://dx.doi.org/10.1016/j. eplepsyres.2011.12.014. 24 [21] Amarillo, Y., Mato, G., Nadal, M. S. Analysis of the role of the low threshold currents IT and ih in intrinsic delta oscillations of thalamocortical neurons. Front. Comput. Neurosci., 9, may 2015. URL http://dx.doi.org/10.3389/fncom. 2015.00052. 25 [22] Coulter, D. A., Huguenard, J. R., Prince, D. A. Calcium currents in rat thalamocortical relay neurones: kinetic properties of the transient, low-threshold current. J. Physiol. (Lond.), 414, 587-604, Jul 1989. 25 [23] Adrian, E. D., Zotterman, Y. The impulses produced by sensory nerve-endings. The Journal of Physiology, 61 (2), 151-171, apr 1926. URL http://dx.doi.org/ 10.1113/jphysiol.1926.sp002281. 27 [24] Hillyard, S. A., Vogel, E. K., Luck, S. J. Sensory gain control (amplication) as a mechanism of selective attention: electrophysiological and neuroimaging evidence. Philosophical Transactions of the Royal Society B: Biological Sciences, 353 (1373), 1257-1270, aug 1998. URL http://dx.doi.org/10.1098/rstb.1998.0281. 32 [25] Masson, G. L., Masson, S. R.-L., Debay, D., Bal, T. Feedback inhibition controls spike transfer in hybrid thalamic circuits. Nature, 417 (6891), 854-858, jun 2002. URL http://dx.doi.org/10.1038/nature00825. 32 [26] Dionne, V. E. Synaptic noise. En: Membranes, Channels, and Noise, pags. 139- 159. Springer Science Business Media, 1984. URL http://dx.doi.org/10.1007/ 978-1-4684-4850-4_5. 33 [27] Destexhe, A., Rudolph-Lilith, M. Neuronal Noise. Springer Science Business Media, 2012. URL http://dx.doi.org/10.1007/978-0-387-79020-6. 33 [28] Verveen, A. Fluctuation in excitability. research report on signal transmission in nerve bers. Netherlands Central Institute for Brain Research, 9, dec 2015. 33 [29] Kohn, A. Computer simulation of noise resulting from random synaptic activities. Computers in Biology and Medicine, 27 (4), 293-308, jul 1997. URL http://dx. doi.org/10.1016/S0010-4825(97)00024-3. 33 [30] Chance, F. S., Abbott, L., Reyes, A. D. Gain modulation from background synaptic input. Neuron, 35 (4), 773-782, aug 2002. URL http://dx.doi.org/10. 1016/S0896-6273(02)00820-6. 33, 34 [31] Fellous JM, D. A. S. T., Rudolph M. Synaptic background noise controls the input/output characteristics of single cells in an in vitro model of in vivo activity. Neuron, 122 (3), 811-829, 2003. 33 [32] Wolfart, J., Debay, D., Masson, G. L., Destexhe, A., Bal, T. Synaptic background activity controls spike transfer from thalamus to cortex. Nature Neuroscience, 8 (12), 1760-1767, oct 2005. URL http://dx.doi.org/10.1038/nn1591. 33, 53 [33] Destexhe, A. e. a. N. . . P., Okamura, Y. \FLUCTUATING SYNAPTIC CONDUCTANCES RECREATE IN VIVO-LIKE ACTIVITY IN NEOCORTICAL NEURONS.". Neuroscience, 10 (7), 13-24, 2001. 33, 34 [34] Behuret, S., Deleuze, C., Bal, T. Corticothalamic synaptic noise as a mechanism for selective attention in thalamic neurons. Frontiers in Neural Circuits, 9, dec 2015. URL http://dx.doi.org/10.3389/fncir.2015.00080. 33 [35] Carnevale, N. T., Hines, M. L. The NEURON Book. Cambridge University Press (CUP), 2006. URL http://dx.doi.org/10.1017/CBO9780511541612. 37, 46 [36] Nowotny, T. Stdpc 2011. En: Manual. Centre for Computational Neuroscience and Robotics, 2011. 46 [37] Destexhe, A. e. a. \Synthesis of Models for Excitable Membranes,Synaptic Transmission and Neuromodulation Using a Common Kinetic Formalism". Journal of computational Neuroscience, 1 (1), 195{230, 1994. 46 [38] Lee, J., Kim, D., Shin, H.-S. Lack of delta waves and sleep disturbances during nonrapid eye movement sleep in mice lacking 1g-subunit of t-type calcium channels. Proceedings of the National Academy of Sciences, 101 (52), 18195-18199, dec 2004. URL http://dx.doi.org/10.1073/pnas.0408089101. 47 [39] Rush, M. E., Rinzel, J. Analysis of bursting in a thalamic neuron model. Biological cybernetics, 71 (4), 281-291, 1994. 47 [40] McCormick, D. A., Huguenard, J. R. A model of the electrophysiological properties of thalamocortical relay neurons. Journal of Neurophysiology, 68 (4), 1384-1400, 1992. 47 [41] Hughes, S. W., Lorincz, M., Cope, D. W., Crunelli, V. Using the dynamic clamp to dissect the properties and mechanisms of intrinsic thalamic oscillations. En: Dynamic-Clamp, pags. 321-345. Springer, 2009. 47, 65 [42] Noebels, J. L. The voltage-gated calcium channel and absence epilepsy, 2012. 50, 65 [43] Budde, T., Caputi, L., Kanyshkova, T., Staak, R., Abrahamczik, C., Munsch, T., et al. Impaired regulation of thalamic pacemaker channels through an imbalance of subunit expression in absence epilepsy. The Journal of neuroscience, 25 (43), 9871-9882, 2005. 50, 65 [44] Ludwig, A., Budde, T., Stieber, J., Moosmang, S., Wahl, C., Holtho, K., et al. Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel hcn2. The EMBO journal, 22 (2), 216-224, 2003. 50, 65 [45] Huang, C.-W., Kuo, C.-C. Flow-and voltage-dependent blocking eect of ethosuximide on the inward rectier k+ (kir2. 1) channel. P ugers Archiv-European Journal of Physiology, 467 (8), 1733-1746, 2015. 50, 65 [46] Connor, J. A., Stevens, C. F. Voltage clamp studies of a transient outward membrane current in gastropod neural somala. The Journal of Physiology, 213, 21-30, 1971. 54 [47] Connor, J. A., Stevens, C. F. Prediction of repetitive ring behaviour from voltage clamp data on an isolated neurone soma. The Journal of Physiology, 213, 31-53, 1971. 54 [48] Nadal, M. S., Ozaita, A., Amarillo, Y., de Miera, E. V.-S., Ma, Y., Mo, W., et al. The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal a-type k channels. Neuron, 37 (3), 449-461, feb 2003. URL http://dx.doi.org/10.1016/S0896-6273(02)01185-6. 54 [49] RAMCHARAN, E. J., GNADT, J. W., Sherman, S. M. Burst and tonic ring in thalamic cells of unanesthetized, behaving monkeys. Visual neuroscience, 17 (01), 55-62, 2000. 58 [50] Fanselow, E. E., Sameshima, K., Baccala, L. A., Nicolelis, M. A. Thalamic bursting in rats during dierent awake behavioral states. Proceedings of the National Academy of Sciences, 98 (26), 15330-15335, 2001. 58 [51] Elijah, D. H., Samengo, I., Montemurro, M. A. Thalamic neuron models encode stimulus information by burst-size modulation. Frontiers in computational neuroscience, 9, 2015. 58 [52] Reinagel, P., Godwin, D., Sherman, S. M., Koch, C. Encoding of visual information by lgn bursts. Journal of neurophysiology, 81 (5), 2558-2569, 1999. 58 [53] Puil, E., Meiri, H., Yarom, Y. Resonant behavior and frequency preferences of thalamic neurons. Journal of neurophysiology, 71 (2), 575-582, 1994. 59 [54] Patel, A. X., Murphy, N., Burdakov, D. Tuning low-voltage-activated a-current for silent gain modulation. Neural computation, 24 (12), 3181-3190, 2012. 66
Materias:Medicina > Neurociencias
Divisiones:Gcia. de área de Investigación y aplicaciones no nucleares > Gcia. de Física > Sistemas complejos y altas energías > Física estadística interdisciplinaria
Código ID:575
Depositado Por:Tamara Cárcamo
Depositado En:21 Abr 2017 18:11
Última Modificación:21 Abr 2017 18:11

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