Browning KN, Wan S, Baptista V, Travagli RA. Vanilloid, purinergic, and CCK receptors activate glutamate release on single neurons of the nucleus tractus solitarius centralis. Am J Physiol Regul Integr Comp Physiol 301: R394 -R401, 2011. First published May 4, 2011 doi:10.1152/ajpregu.00054.2011.-Baroreceptor inputs to nucleus of the tractus solitarius medialis (mNTS) neurons can be differentiated, among other features, by their response to vanilloid or purinergic agonists, active only on C-or A-fibers, respectively. A major aim of this study was to examine whether neurons of NTS centralis (cNTS), a subnucleus dominated by esophageal inputs, exhibit a similar dichotomy. Since it has been suggested that cholecystokinin (CCK), exerts its gastrointestinal (GI)-related effects via paracrine activation of vagal afferent C-fibers, we tested whether CCK-sensitive fibers impinging upon cNTS neurons are responsive to vanilloid but not purinergic agonists. Using whole cell patch-clamp recordings from cNTS, we recorded miniature excitatory postsynaptic currents (mEPSCs) to test the effects of the vanilloid agonist capsaicin, the purinergic agonist ␣,␤-methylene-ATP (␣,␤-Met-ATP), and/or CCK-octapeptide (CCK-8s). ␣,␤-Met-ATP, capsaicin; and CCK-8s increased EPSC frequency in 37, 71, and 46% of cNTS neurons, respectively. Approximately 30% of cNTS neurons were responsive to both CCK-8s and ␣,␤-Met-ATP, to CCK-8s and capsaicin, or to ␣,␤-Met-ATP and capsaicin, while 32% of neurons were responsive to all three agonists. All neurons responding to either ␣,␤-Met-ATP or CCK-8s were also responsive to capsaicin. Perivagal capsaicin, which is supposed to induce a selective degeneration of C-fibers, decreased the number of cNTS neurons responding to capsaicin or CCK-8s but not those responding to ␣,␤-Met-ATP. In summary, GI inputs to cNTS neurons cannot be distinguished on the basis of their selective responses to ␣,␤-Met-ATP or capsaicin. Our data also indicate that CCK-8s increases glutamate release from purinergic and vanilloid responsive fibers impinging on cNTS neurons. brainstem; vagus; electrophysiology VAGAL AFFERENT (SENSORY) FIBERS convey a vast amount of information about the physiological state of the thoracic and abdominal viscera to the central nervous system, specifically, to the nucleus of the tractus solitarius (NTS). Vagal afferent fibers are organized in the NTS in an overlapping topographical manner. Sensory afferents from the stomach and intestine, for example, terminate in the subnuclei commissuralis and medialis, inputs from the stomach terminate in the subnuclei medialis and gelatinosus, while inputs from the esophagus terminate in the subnucleus centralis (49). Vagal afferent fibers relay this visceral information by a mixture of myelinated (A-type) and unmyelinated (C-type) axons. These two types of afferent fibers display distinct physiological and functional characteristics, including different sensory modalities and conduction velocities and may regulate autonomic homeostatic and regulatory reflexes di...