Development of electrophysiological and morphological diversity in autonomic neurons.

Abstract

The generation of neuronal diversity requires the coordinated development of differential patterns of ion channel expression along with characteristic differences in dendritic geometry, but the relations between these phenotypic features are not well known. We have used a combination of intracellular recordings, morphological analysis of dye-filled neurons, and stereological analysis of immunohistochemically labeled sections to investigate the development of characteristic electrical and morphological properties of functionally distinct populations of sympathetic neurons that project from the celiac ganglion to the splanchnic vasculature or the gastrointestinal tract of guinea pigs. At early fetal stages, neurons were significantly more depolarized at rest compared with neurons at later stages, and they generally fired only a single action potential. By mid fetal stages, rapidly and slowly adapting neurons could be distinguished with a topographic distribution matching that found in adult ganglia. Most rapidly adapting neurons (phasic neurons) at this age had a long afterhyperpolarization (LAH) characteristic of mature vasomotor neurons and were preferentially located in the lateral poles of the ganglion, where most neurons contained neuropeptide Y. Most early and mid fetal neurons showed a weak M current, which was later expressed only by rapidly-adapting and LAH neurons. Two different A currents were present in a subset of early fetal neurons and may indicate neurons destined to develop a slowly adapting phenotype (tonic neurons). The size of neuronal cell bodies increased at a similar rate throughout development regardless of their electrical or neurochemical phenotype or their topographical location. In contrast, the rate of dendritic growth of neurons in medial regions of the ganglion was significantly higher than that of neurons in lateral regions. The apparent cell capacitance was highly correlated with the surface area of the soma but not the dendritic tree of the developing neurons. These results demonstrate that the well-defined functional populations of neurons in the celiac ganglion develop their characteristic electrophysiological and morphological properties during early fetal stages of development. This is after the neuronal populations can be recognized by their neurochemical and topographical characteristics but long before the neurons have finished growing. Our data provide strong circumstantial evidence that the development of the full phenotype of different functional classes of autonomic final motor neurons is a multi-step process likely to involve a regulated sequence of trophic interactions.