Distribution and phenotype of Phox2a-containing neurons in the adult sprague-dawley rat.

Phox2a is a transcription factor that plays an essential role, with Phox2b, in the specification of the adrenergic and noradrenergic phenotype in developing brain. Localization of Phox2a in developing brainstem has demonstrated a high degree of correspondence between neurons expressing the transcription factor and those involved in the regulation of autonomic function. Although it is well established that the paralogous gene product Phox2b is widely expressed in adult brain, no study has mapped the distribution of Phox2a in the adult. The data reported here address that void. A well-characterized rabbit polyclonal antiserum was used for immunohistochemical localization of the transcription factor in adult rats. Sections through the rostrocaudal extent of brain were processed for dual immunocytochemical localization of Phox2a and catecholamine enzymes. Adjacent sections were used for dual localization of Phox2a and NADPH diaphorase, a marker of nitric oxide-containing neurons. The data demonstrate that Phox2a is present in all brainstem catecholamine neurons, in circumscribed populations of NADPH(+) neurons, and in a subset of neurons that influences sympathetic and parasympathetic outflow. In addition, Phox2a(+) neurons were observed within diencephalic and brainstem nuclei that regulate behavioral state. Considered with data demonstrating that Phox2a is part of the transcriptional complex that drives expression of dopamine-beta-hydroxylase and can also up-regulate expression of other genes, the data support the conclusion that Phox2a plays an important role in brainstem catecholamine neurotransmission and in the regulation of adaptive homeostatic functions in the adult nervous system.