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Differential Modulation of Neural Network and Pacemaker Activity Underlying Eupnea and Sigh-Breathing Activities

¹Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; ²Departamento de Farmacobiología, Cinvestav-Sede Sur, Mexico City, Federal District, Mexico; ³Department of Psychiatry, University of California–San Francisco, San Francisco, California; ⁴Laboratoire Plasticité et Physio-Pathologie de la Motricité, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6196, Marseille; ⁵Laboratoire de Neurobiologie Genetique et Integrative, Institut Alfred Fessard, Gif sur Yvette, France; and ⁶Department of Organismal Biology, The University of Chicago, Chicago, Illinois

Submitted 25 October 2007; accepted in final form 19 February 2008

Many networks generate distinct rhythms with multiple frequency and amplitude characteristics. The respiratory network in the pre-Bötzinger complex (pre-Böt) generates both the low-frequency, large-amplitude sigh rhythm and a faster, smaller-amplitude eupneic rhythm. Could the same set of pacemakers generate both rhythms? Here we used an in vitro respiratory brainslice preparation. We describe a subset of synaptically isolated pacemakers that spontaneously generate two distinct bursting patterns. These two patterns resemble network activity including sigh-like bursts that occur at low frequencies and have large amplitudes and eupneic-like bursts with higher frequency and smaller amplitudes. Cholinergic neuromodulation altered the network and pacemaker bursting: fictive sigh frequency is increased dramatically, whereas fictive eupneic frequency is drastically lowered. The data suggest that timing and amplitude characteristics of fictive eupneic and sigh rhythms are set by the same set of pacemakers that are tuned by changes in the neuromodulatory state.

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