Raphe neuronal circuits and responses to central and peripheral chemoreceptor stimulation

Abstract

Current models propose that raphe neurons are elements of both central and peripheral chemoreceptor reflex circuits. Focal acidification of the brainstem midline raphe can stimulate breathing and cultured raphe neurons have chemosensitive properties. However, little is known about the responses of individual raphe neurons in vivo and the network that integrates chemoreceptor signals. Using multi-electrode arrays and spike train analysis, we measured the activities of 340 raphe neurons together with the phrenic nerve during sequential transient central and/or peripheral chemoreceptor stimulation via CO2-saturated saline injections in vertebral and carotid arteries, respectively, in 11 decerebrate vagotomized cats. A subset of 267 neurons tested with both stimuli responded to either central (n=44) or peripheral (n=42) chemoreceptor challenges, but not both. Of 66 cells that did respond to both, 30 responded with firing rate changes in the same direction (14 INC, 16 DEC). Among 36 neurons with opposite changes in firing rate, 27 decreased during central chemoreceptor stimulation. Functional connections were detected between neurons in 320 of 4,021 pairs. Central cross-correlogram features include 136 peaks indicative of shared inputs of like sign and 31 troughs suggesting inputs with opposite actions. The presence of offset features, including 88 peaks and 33 troughs, suggest pauci-synaptic excitatory and inhibitory interactions, respectively. The results demonstrate functional convergence of central and peripheral chemoreceptor effects on raphe neuronal assemblies and suggest circuit chains and loops appropriate for gain control of both chemoreceptive inputs to the brainstem cardiorespiratory network. Support: NS19814.