A GROUP OF NON-SEROTONERGIC CELLS IS CO2-STIMULATED IN THE MEDULLARY RAPHE

Serotonin/substance P synthesizing cells in the raphe nuclei of the brain are candidates for designation as central chemoreceptors that are stimulated by CO2/pH. We have previously demonstrated that these neurons are CO2-stimulated in situ. Evidence also suggests that CO2-inhibited raphe neurons recorded in vitro and in situ synthesize GABA. Unknown is whether there are other types of chemosensitive cells in the raphe. Here, we showed that a previously unrecognized pool of raphe neurons also exhibit chemosensitivity, and that they are not serotonergic. We used extracellular recording of individual raphe neurons in the unanesthetized juvenile rat in situ perfused decerebrate brainstem preparation to assess chemosensitivity of raphe neurons. Subsequent juxtacellular labeling of individually recorded cells, and immunohistochemistry for the serotonin synthesizing enzyme tryptophan hydroxylase and for neurokinin-1 receptor (NK1R; the receptor for substance P) indicated a group of CO2-stimulated cells that are not serotonergic, but express NK1R and are closely apposed to surrounding serotonergic cells. CO2-stimulated 5-HT and non-5-HT cells constitute distinct groups that have different firing characteristics and hypercapnic sensitivities. Non-5-HT cells fire faster and are more robustly stimulated by CO2 than are 5-HT cells. Thus, we have characterized a previously unrecognized type of CO2-stimulated medullary raphe neuron that is not serotonergic, but may receive input from neighboring serotonin/substance P synthesizing chemosensitive neurons. The potential network properties of the three types of chemosensitive raphe neurons (the present non-5-HT cells, serotonergic cells, and CO2-inhibited cells) remain to be elucidated. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.