The Role of Glutamate in the Transmission of the Hypoxic Input to Respiration Through the Nucleus of the Tractus Solitarius

Abstract

The hypoxic drive to respiration provided from the chemoreceptors of the carotid body is organized in the nucleus of the tractus solitarius (NTS) at a localized site just caudal to obex¹. Specific evidence that terminals at this particular site are involved in respiratory chemoreflexes was provided by lesioning studies utilizing kainic acid (KA), a neurotoxin which acts through a glutamatergic mechanism². This observation sugguests that glutamate may represent the neurotransmitter at the first central synapse of chemoreceptor afferents, as has been argued for baroreceptor afferents synapsing more rostrally in the NTS^3,4. Support for this hypothesis is provided by the demonstration that glutamate concentrations are high in the region⁵ and increase, as does glutamate turnover, during hypoxia⁶. We have tested respiratory responses to the injection of kainic acid, glutamate, and two glutamate antagonists into the appropriate region of the NTS in rats. Measurements of the respiratory responses of intact animals required that the effects be of widespread distribution rather than localized, as may occur when glutamate is applied by iontophoresis^7,8. Also, minimal doses must sometimes be larger than those used to elicit changes of motoneuron output⁹. The more desirable evidence of functional significance, the loss of a defined response¹⁰ was sought by testing the effect of injection of glutamate antagonists on the hypoxic response of respiration. Control experiments were devised to reduce the possibility that effects might have been produced at sites distant from those of the injections. The experiments provided consistent evidence for the involvement of glutamate in the transmission of input from carotid body afferent terminals to neurons of the NTS.