Chemical activation of pre-Bötzinger complex in vivo reduces respiratory network complexity

In the in vivo anesthetized adult cat model, multiple patterns of inspiratory motor discharge have been recorded in response to chemical stimulation and focal hypoxia of the pre-Bötzinger complex (pre-BötC), suggesting that this region may participate in the generation of complex respiratory dynamics. The complexity of a signal can be quantified using approximate entropy (ApEn) and multiscale entropy (MSEn) methods, both of which measure the regularity (orderliness) in a time series, with the latter method taking into consideration temporal fluctuations in the underlying dynamics. The current investigation was undertaken to examine the effects of pre-BötC-induced excitation of phasic phrenic nerve discharge, which is characterized by high-amplitude, rapid-rate-of-rise, short-duration bursts, on the complexity of the central inspiratory neural controller in the vagotomized, chloralose-anesthetized adult cat model. To assess inspiratory neural network complexity, we calculated the ApEn and MSEn of phrenic nerve bursts during eupneic (basal) discharge and during pre-BötC-induced excitation of phasic inspiratory bursts. Chemical stimulation of the pre-BötC using DL-homocysteic acid (DLH; 10 mM; 10-20 nl; n=10) significantly reduced the ApEn from 0.982+/-0.066 (mean+/-SE) to 0.664+/-0.067 (P<0.001) followed by recovery ( approximately 1-2 min after DLH) of the ApEn to 1.014+/-0.067; a slightly enhanced magnitude reduction in MSEn was observed. Focal pre-BötC hypoxia (induced by sodium cyanide; NaCN; 1 mM; 20 nl; n=2) also elicited a reduction in both ApEn and MSEn, similar to those observed for the DLH-induced response. These observations demonstrate that activation of the pre-BötC reduces inspiratory network complexity, suggesting a role for the pre-BötC in regulation of complex respiratory dynamics.