BDNF is a target-derived survival factor for arterial baroreceptor and chemoafferent primary sensory neurons

Brain-derived neurotrophic factor (BDNF) supports survival of 50% of visceral afferent neurons in the nodose/petrosal sensory ganglion complex (NPG; Ernfors et al., 1994a; Jones et al., 1994; Conover et al., 1995; Liu et al., 1995; Erickson et al., 1996), including arterial chemoafferents that innervate the carotid body and are required for development of normal breathing (Erickson et al., 1996). However, the relationship between BDNF dependence of visceral afferents and the location and timing of BDNF expression in visceral tissues is unknown. The present study demonstrates that BDNF mRNA and protein are transiently expressed in NPG targets in the fetal cardiac outflow tract, including baroreceptor regions in the aortic arch, carotid sinus, and right subclavian artery, as well as in the carotid body. The period of BDNF expression corresponds to the onset of sensory innervation and to the time at which fetal NPG neurons are BDNF-dependent in vitro. Moreover, baroreceptor innervation is absent in newborn mice lacking BDNF. In addition to vascular targets, vascular afferents themselves express high levels of BDNF, both during and after the time they are BDNF-dependent. However, endogenous BDNF supports survival of fetal NPG neurons in vitro only under depolarizing conditions. Together, these data indicate two roles for BDNF during vascular afferent pathway development; initially, as a target-derived survival factor, and subsequently, as a signaling molecule produced by the afferents themselves. Furthermore, the fact that BDNF is required for survival of functionally distinct populations of vascular afferents demonstrates that trophic requirements of NPG neurons are not modality-specific but may instead be associated with innervation of particular organ systems.