Ih activation is required for sigh but not for eupnea generation. Ih activation is required for sigh but not for eupnea generation. A, Top, Simultaneous current-clamp recording of an inspiratory neuron (top trace) with integrated preBötC activity recording (bottom trace). Bottom left, Currents recorded in voltage clamp (bottom trace sets; i) evoked by hyperpolarizing voltage steps (top trace set; V) from a holding potential of −50 mV in control conditions (CTL) and in the presence of 50 µM ZD 7288 to block Ih. Bottom right, Amplitude of h current versus membrane potential under control conditions (black circles) and in the presence of ZD 7288 (gray circles). Ih was fully blocked by ZD 7288. B, In vitro extracellular recordings of preBötC activity in control (top trace) and in the presence of 50 µM ZD 7288. C, In silico experiments that included Ih in the eupnea compartment model only (top), the sigh compartment only (middle), and in both compartments (bottom). The sigh bursts exhibit a biphasic shape only when Ih is present in both compartments. D, Voltage traces of in silico experiment with changes in Ih from its control value gh = 2 nS, (top) to gh = 0 nS (bottom). Both in silico and in vitro blockade of Ih selectively prevents sigh-burst generation. Orange stars indicate sigh events. Natalia Toporikova et al. eneuro 2015;2:ENEURO.0074-14.2015 ©2015 by Society for Neuroscience