PT - JOURNAL ARTICLE AU - Hidehiko Koizumi AU - Jeffrey C. Smith TI - Persistent Na<sup>+</sup> and K<sup>+</sup>-Dominated Leak Currents Contribute to Respiratory Rhythm Generation in the Pre-Bötzinger Complex <em>In Vitro</em> AID - 10.1523/JNEUROSCI.3916-07.2008 DP - 2008 Feb 13 TA - The Journal of Neuroscience PG - 1773--1785 VI - 28 IP - 7 4099 - http://www.jneurosci.org/content/28/7/1773.short 4100 - http://www.jneurosci.org/content/28/7/1773.full SO - J. Neurosci.2008 Feb 13; 28 AB - A central problem in analyzing neural circuit function is establishing how intrinsic neuronal conductances contribute to the generation of network activity. We used real-time calcium activity imaging combined with whole-cell patch-clamp recording to analyze contributions of subthreshold conductances in the excitatory rhythm-generating network in the respiratory pre-Bötzinger complex (pre-BötC) of neonatal rat in vitro brainstem slice preparations. Voltage-clamp ramp recordings from imaged pre-BötC neurons revealed that persistent sodium (NaP) and K+-dominated leak currents primarily contribute to subthreshold I–V relations. We quantified NaP and leak conductance densities (g/Cm) in intrinsic oscillatory bursters and intrinsically nonbursters, the two main electrophysiological phenotypes of inspiratory neurons within the pre-BötC. Densities of gNaP were significantly higher for intrinsic bursters, whereas leak conductance densities were not significantly different between intrinsic bursters and nonbursters. By pharmacologically manipulating gNaP and/or gLeak directly within the pre-BötC, we could modulate network oscillation frequency over a wide dynamic range and cause transitions between oscillatory and quiescent states. These results were consistent with models of the pre-BötC excitatory network consisting of heterogeneous mixtures of intrinsic bursters and nonintrinsic bursters incorporating gNaP and gLeak with parameter values found experimentally. We propose a paradigm whereby NaP and Leak represent a functional set of subthreshold conductances that endow the pre-BötC with rhythmogenic properties and represent targets for modulatory control of inspiratory rhythm generation.