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Transient attenuation of CO2 sensitivity after neurotoxic lesions in the medullary raphe area of awake goats. J Appl Physiol (1985) 2004 Dec;97(6):2236-47



Pubmed ID




Scopus ID

2-s2.0-9244237596   40 Citations


The major objective of this study was to gain insight into whether under physiological conditions medullary raphe area neurons influence breathing through CO(2)/H(+) chemoreceptors and/or through a postulated, nonchemoreceptor modulatory influence. Microtubules were chronically implanted into the raphe of adult goats (n = 13), and breathing at rest (awake and asleep), breathing during exercise, as well as CO(2) sensitivity were assessed repeatedly before and after sequential injections of the neurotoxins saporin conjugated to substance P [SP-SAP; neurokinin-1 receptor (NK1R) specific] and ibotenic acid (IA; nonspecific glutamate receptor excitotoxin). In all goats, microtubule implantation alone resulted in altered breathing periods, manifested as central or obstructive apneas, and fractionated breathing. The frequency and characteristics of the altered breathing periods were not subsequently affected by injections of the neurotoxins (P > 0.05). Three to seven days after SP-SAP or subsequent IA injection, CO(2) sensitivity was reduced (P < 0.05) by 23.8 and 26.8%, respectively, but CO(2) sensitivity returned to preinjection control values >7 days postinjection. However, there was no hypoventilation at rest (awake, non-rapid eye movement sleep, or rapid eye movement sleep) or during exercise after these injections (P > 0.05). The neurotoxin injections resulted in neuronal death greater than three times that with microtubule implantation alone and reduced (P < 0.05) both tryptophan hydroxylase-expressing (36%) and NK1R-expressing (35%) neurons at the site of injection. We conclude that both NK1R- and glutamate receptor-expressing neurons in the medullary raphe nuclei influence CO(2) sensitivity apparently through CO(2)/H-expressing chemoreception, but the altered breathing periods appear unrelated to CO(2) chemoreception and thus are likely due to non-chemoreceptor-related neuromodulation of ventilatory control mechanisms.

Author List

Hodges MR, Opansky C, Qian B, Davis S, Bonis J, Bastasic J, Leekley T, Pan LG, Forster HV


Hubert V. Forster PhD Professor in the Physiology department at Medical College of Wisconsin
Matthew R. Hodges PhD Associate Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Carbon Dioxide
Cell Count
Chemoreceptor Cells
Excitatory Amino Acid Agonists
Ibotenic Acid
Medulla Oblongata
Raphe Nuclei
Respiratory Mechanics
Ribosome Inactivating Proteins, Type 1
Substance P
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1