Involvement of glutamate in transmission of afferent constrictive inputs from the airways to the nucleus tractus solitarius in ferrets

In this study, we identified the neurons within nucleus tractus solitarius (nTS) activated by stimulation of airway sensory systems and examined the expression of AMPA receptor subtype(s) by these cells. We also investigated the possible involvement of endogenously released glutamate and AMPA receptors in the transmission of excitatory inputs from the sensory system of the respiratory tract to the neurons of the nTS. In these experiments we used: (1) immunodetection of c-fos encoded protein (cFos) expression to identify the nTS neurons activated by the stimulation of the airway sensory system; (2) receptor immunochemistry and confocal microscopy to determine the receptor(s) expressed by activated nTS neurons; (3) microdialysis to measure glutamate release, and (4) physiological measurements to examine the effects of selective receptor blockers, and thereby define the role of the glutamate and AMPA glutamatergic receptor subtype(s) in reflexly induced airway constriction. The results showed that activation of airway sensory receptors, by inhalation of aerosolized histamine or capsaicin, induced cFos expression in a subset of nTS neurons that also expressed the AMPA subtype of glutamate receptors. Furthermore, activation of sensory bronchoconstrictive receptors induced glutamate release within nTS, and blockade of the AMPA receptor subtype within nTS inhibited reflexly increased cholinergic outflow to the airways. These data indicate for the first time that glutamate and AMPA receptor signaling pathways are involved in the transmission of afferent inputs from the airways to the nTS, and in mediating reflex airway constriction.