Excitatory amino acid-mediated chemoreflex excitation of respiratory neurones in rostral ventrolateral medulla in rats

1. In anaesthetized rats, extracellular and intracellular recordings were made from 119 respiratory neurones in the rostroventrolateral reticular nucleus (RVL) of the medulla oblongata. 2. Two types of active respiratory neurones were detected in RVL: expiratory (E) and pre-inspiratory (Pre-I), based on the relationship between their discharge and that of the phrenic nerve. Some Pre-I but none of the E neurones could be antidromically excited from the C-3-C-4 level of the spinal cord. 3. E and Pre-I neurones of RVL were excited by stimulation of the arterial chemoreceptors by a close arterial injection of sodium cyanide. The reflex excitation of RVL E neurones was preceded by increased phrenic nerve activity, while the excitation of RVL Pre-I neurones preceded the increases in phrenic nerve activity. 4. The chemoreflex excitation of the two types of RVL respiratory neurones as well as their resting discharge was abolished or significantly depressed by microionophoresis of kynurenate, a wide-spectrum antagonist of excitatory amino acid receptors, while xanthurenate, an inactive analogue of kynurenate, was without effect. 5. In ventilated rats, bilateral microinjection into RVL of kynurenate, but not xanthurenate, abolished resting activity and chemoreflex excitation of phrenic nerve activity, whilst in spontaneously breathing rats, kynurenate microinjection into RVL produced apnea and silenced phrenic nerves. 6. We conclude: (a) chemoreflex excitation of the phrenic nerves is mediated by stimulating Pre-I neurones of RVL by excitatory amino acidergic inputs and (b) RVL Pre-I neurones may directly and/or indirectly excite spinal phrenic motor neurones and hence are involved in inspiratory rhythmogenesis.