Decreased CSF pH at ventral brain stem induces widespread c-Fos immunoreactivity in rat brain neurons

Physiological evidence has indicated that central respiratory chemosensitiv ity may be ascribed to neurons located at the ventral medullary surface (VM S); however, in recent years, multiple sites have been proposed. Because c- Fos immunoreactivity is presumed to identify primary cells as well as secon d- and third-order cells that are activated by a particular stimulus, we hy pothesized that activation of VMS cells using a known adequate respiratory stimulus, HI, would induce production of c-Fos in cells that participate in the central pH-sensitive respiratory chemoreflex loop. In this study, stim ulation of rostral and caudal VMS respiratory chemosensitive sites in chlor alose-urethane-anesthetized rats with acidic (pH 7.2) mock cerebrospinal fl uid induced c-Fos protein immunoreactivity in widespread brain sites, such as VMS, ventral pontine surface, retrotrapezoid, medial and lateral parabra chial, lateral reticular nuclei, cranial nerves VII and X nuclei, A(1) and C-1 areas, area postrema, locus coeruleus, and paragigantocellular nuclei. At the hypothalamus, the c-Fos reaction product was seen in the dorsomedial , lateral hypothalamic, supraoptic, and periventricular nuclei. These resul ts suggest that 1) multiple c-Fos-positive brain stem and hypothalamic stru ctures may represent part of a neuronal network responsive to cerebrospinal fluid pH changes at the VMS, and 2) VMS pH-sensitive neurons project to wi despread regions in the brain stem and hypothalamus that include respirator y and cardiovascular control sites.