Role of Parafacial Nuclei in Control of Breathing in Adult Rats

Contiguous brain regions associated with a given behavior are increasingly being divided into subregions associated with distinct aspects of that behavior. Using recently developed neuronal hyperpolarizing technologies, we functionally dissect the parafacial region in the medulla, which contains key elements of the central pattern generator for breathing that are important in central CO2-chemoreception and for gating active expiration. By transfecting different populations of neighboring neurons with allatostatin or HM4D G(i/o)-coupled receptors, we analyzed the effect of their hyperpolarization on respiration in spontaneously breathing vagotomized urethaneanesthetized rats. We identify two functionally separate parafacial nuclei: ventral (pF(V)) and lateral (pF(L)). Disinhibition of the pF(L) with bicuculline and strychnine led to active expiration. Hyperpolarizing pF(L) neurons had no effect on breathing at rest, or changes in inspiratory activity induced by hypoxia and hypercapnia; however, hyperpolarizing pF(L) neurons attenuated active expiration when it was induced by hypercapnia, hypoxia, or disinhibition of the pF(L). In contrast, hyperpolarizing pF(V) neurons affected breathing at rest by decreasing inspiratory-related activity, attenuating the hypoxia-and hypercapnia-induced increase in inspiratory activity, and when present, reducing expiratory-related abdominal activity. Together with previous observations, we conclude that the pF(V) provides a generic excitatory drive to breathe, even at rest, whereas the pF(L) is a conditional oscillator quiet at rest that, when activated, e.g., during exercise, drives active expiration.