Emetic reflex arc revealed by expression of the immediate-early gene c- fos in the cat

Abstract

The organization of the central neuronal circuitry that produces vomiting was explored by mapping the distribution of c-fos protein (Fos)-like immunoreactivity (FLI) as a monitor of functional activity. The brainstem and spinal cord were examined in cats administered multiple emetic drugs (cisplatin, lobeline, protoveratrine, naloxone, apomorphine) or control saline injections. Some animals were decerebrated, paralyzed, and artificially ventilated to avoid possible Fos expression induced by sensory feedback or fluid depletion during vomiting. Fictive vomiting was identified in these animals by a characteristic pattern of respiratory muscle nerve (phrenic and abdominal) coactivation. Tissues were immunoprocessed using an antibody raised against amino acids 1-131 of Fos and the avidin-biotin peroxidase complex method. Enhanced nuclear FLI was observed in experimental animals along portions of the sensorimotor emetic reflex arc, including the nodose ganglia, area postrema, nuclei of the solitary tract (especially medial and subpostrema subnuclei), intermediate reticular zone of the lateral tegmental field, nucleus retroambiguus, C2 inspiratory propriospinal cell region, and dorsal vagal and phrenic motor nuclei. Enhanced FLI was also detected in the raphe magnus, subretrofacial nucleus, and spinal dorsal horn. Regions showing no recognizable differences in FLI between experimental and control animals included the vestibular, cochlear, spinal trigeminal, subtrigeminal, and lateral reticular nuclei. Only minor differences were observed in the distributions of FLI between intact and decerebrate animals. No unique, well-defined group of labeled neurons that might function as a "vomiting center" could be identified. Instead, the pattern of c-fos expression suggests that neurons involved in coordinating the emetic response may radiate from the area postrema and nucleus of the solitary tract to an arc in the lateral tegmental field implicated in somato-autonomic integration.