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The Journal of Neuroscience, April 6, 2005, 25(14):3601-3612; doi:10.1523/JNEUROSCI.4290-04.2005

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Behavioral/Systems/Cognitive
Modeling Spontaneous Activity in the Developing Spinal Cord Using Activity-Dependent Variations of Intracellular Chloride

Cristina Marchetti,^1,2 Joel Tabak,¹ Nikolai Chub,¹ Michael J. O'Donovan,¹ and John Rinzel^2,3

¹Laboratory of Neural Control, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, and ²Center for Neural Science and ³Courant Institute of Mathematical Sciences, New York University, New York, New York 10003

We investigated how spontaneous activity is generated in developing, hyperexcitable networks. We focused our study on the embryonic chick spinal cord, a preparation that exhibits rhythmic discharge on multiple timescales: slow episodes (lasting minutes) and faster intraepisode cycling (1 Hz frequency). For this purpose, we developed a mean field model of a recurrent network with slow chloride dynamics and a fast depression variable. We showed that the model, in addition to providing a biophysical mechanism for the slow dynamics, was able to account for the experimentally observed activity. The model made predictions on how interval and duration of episodes are affected when changing chloride-mediated synaptic transmission or chloride flux across cell membrane. These predictions guided experiments, and the model results were compared with experimental data obtained with electrophysiological recordings. We found agreement when transmission was affected through changes in synaptic conductance and good qualitative agreement when chloride flux was varied through changes in external chloride concentration or in the rate of the Na⁺-K⁺-2Cl^- cotransporter. Furthermore, the model made predictions about the time course of intracellular chloride concentration and chloride reversal potential and how these are affected by changes in synaptic conductance. Based on the comparison between modeling and experimental results, we propose that chloride dynamics could be an important mechanism in rhythm generation in the developing chick spinal cord.

Key words: spontaneous activity; network; development; chloride; spinal cord; modeling

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Received Oct 14, 2004; revised February 4, 2005; accepted February 19, 2005.

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				K. Achilles, A. Okabe, M. Ikeda, C. Shimizu-Okabe, J. Yamada, A. Fukuda, H. J. Luhmann, and W. Kilb Kinetic Properties of Cl Uptake Mediated by Na+-Dependent K+-2Cl Cotransport in Immature Rat Neocortical Neurons J. Neurosci., August 8, 2007; 27(32): 8616 - 8627. [Abstract] [Full Text] [PDF]

				N. Chub, G. Z. Mentis, and M. J. O'Donovan Chloride-Sensitive MEQ Fluorescence in Chick Embryo Motoneurons Following Manipulations of Chloride and During Spontaneous Network Activity J Neurophysiol, January 1, 2006; 95(1): 323 - 330. [Abstract] [Full Text] [PDF]

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