The development of postganglionic sympathetic neurons: coordinating neuronal differentiation and diversification

doi:10.1016/S1566-0702(01)00336-8

Autonomic Neuroscience

Volume 94, Issues 1–2, 10 December 2001, Pages 1-13

https://doi.org/10.1016/S1566-0702(01)00336-8 Get rights and content

Abstract

The fine-tuned operation of the nervous system is accomplished by a diverse set of neurons which differ in their morphology, biochemistry and, consequently, their functional properties. The accurate interconnection between different neuron populations and their target tissues is the prerequisite for physiologically appropriate information processing. This is exemplified by the regulatory action of the autonomic nervous system in vertebrates to sustain homeostasis under changing physiological demands. For this purpose, the coordination of divergent regulatory responses is required in a multitude of tissues spread over the entire body. To meet this task, diverse neuronal populations interact at different levels.

In the sympathetic system, chemical relations between preganglionic and postganglionic neurons appear to differ along the rostrocaudal axis. In addition, postganglionic neurons innervating different target tissues at a segmental level have distinct properties. Differences in their preganglionic innervation and their integrative membrane properties result in diverse activation patterns upon reflex stimulation. Moreover, postganglionic neurons differ in the transmitter molecules they employ to convey information to the target tissues. The segregation of noradrenaline and acetylcholine to different populations of postganglionic sympathetic neurons is well established.

A combination of cellular and molecular approaches has begun to uncover how such a complex system may be generated during development. Growth and transcription factors involved in noradrenergic and cholinergic differentiation are characterised. Interestingly, they can also promote the expression of proteins involved in transmitter secretion. As the proteins participating in the vesicle cycle are expressed in many neuron populations, whereas the enzymes of transmitter biosynthesis are restricted to subpopulations of neurons, the findings suggest that early in neuronal development subpopulation-specific and more widely expressed neuronal properties can be commonly induced. Still, many details concerning the signals involved in the induction of the neurotransmitter synthesis and release machinery remain to be worked out. Likewise, the regulatory processes resulting in differences of electrophysiological membrane properties and the specific recognition between pre- and postganglionic neurons have to be determined. Ultimately, this will lead to an understanding at the molecular level of the development of a nervous system with diverse neuronal populations that are specifically interconnected to distinct input neurons and target tissues as required for the performance of a complex regulatory function.

Section snippets

Neuronal diversity in the sympathetic postganglionic system

The sympathetic nervous system is a main effector of the autonomic nervous system to maintain homeostatic balance during diverse physiological conditions (Cannon, 1939). To accomplish this task, it provides a general supply of autonomic fibers throughout the body (Langley, 1903) and, at the same time, allows the specific adjustment of end organ responses by the different regulation of distinct target tissues (Jänig, 1985). This is possible due to a specific projection of preganglionic fibers

The induction of the noradrenergic neurotransmitter phenotype—early specification of sympathetic neuroblasts

Histochemical detection of catecholamines in embryonic tissue demonstrated the acquisition of an aminergic phenotype early after formation of chick and rat primary sympathetic ganglia Enemar et al., 1965, Cochard et al., 1978. This differentiation step occurs at a time when sympathetic neuroblasts are still mitotically active Rothman et al., 1978, Rohrer and Thoenen, 1987, several days before location of sympathetic neurons to their definitive positions in the secondary ganglia and before

Cholinergic differentiation of sympathetic neurons—the emergence of diversity at the neurochemical level

During sympathetic ganglion development, cholinergic properties are expressed later than noradrenergic ones, in some cases only after target innervation. In birds as well as mammals, the segregation of cholinergic and noradrenergic properties to different populations of postganglionic sympathetic neurons characterises the situation at advanced developmental stages (see Ernsberger and Rohrer, 1999, for review). Earlier during development, neurons can be found that express both cholinergic and

Development of the transmitter release machinery—coordinating neuronal differentiation and diversification

Differentiating sympathetic precursors express the catecholaminergic transmitter phenotype early during embryonic development. This comprises the enzymes of the noradrenaline biosynthesis cascade and an initially immature form of storage vesicles. With a few days delay, the biosynthesis enzyme and the vesicular transporter characteristic for the cholinergic transmitter phenotype are expressed. These observations prompt the question when the machinery for regulated release of transmitter is

Development of electrical membrane properties—differentiation and diversification to be analysed

The development of those aspects of neuronal function discussed in this review, the neurotransmitter phenotype and the transmitter release machinery, concerns the output properties of neurons.

Less is known about the induction and developmental regulation of the input and integrative properties of sympathetic neurons such as membrane excitability. The diversity of nAChR subunits Mandelzys et al., 1994, Rust et al., 1994, Devay et al., 1994 and of voltage-activated potassium channel subunits

Development of specific projections between preganglionic and postganglionic neurons—more than a century's problem

Observations in the chick embryo indicate that the gross preganglionic projections at the different segmental levels are correct from the outset (Yip, 1990). Rotation of spinal cord segments shows that the preganglionic axonal outgrowth is guided by cues provided by the local environment and not intrinsically by the neurons' segmental origin (Yip et al., 1998). In particular, somitic mesoderm appears crucial for the correct outgrowth of preganglionic axons (Yip, 1996). Moreover, target ganglia

Conclusions

The peripheral sympathetic system employs a range of different neuron populations to evoke specific reflex responses in its diverse target tissues. Differences between postganglionic neuron populations can be observed along the rostrocaudal axes and at the segmental level. They include specific connectivity with preganglionic neurons, the integrative functions of membrane conductances, or the transmitter substances secreted, and produce different activity patterns to elicit appropriate

Acknowledgements

I wish to acknowledge Dr. Wilfried Jänig, Physiologisches Institut, Kiel, Germany, for initialising my interest in the sympathetic nervous system and in the question of how such a complex system can possibly be put together during development. I also wish to thank him for his critical suggestions on the manuscript.

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ReviewThe development of postganglionic sympathetic neurons: coordinating neuronal differentiation and diversification

Abstract

Section snippets

Neuronal diversity in the sympathetic postganglionic system

The induction of the noradrenergic neurotransmitter phenotype—early specification of sympathetic neuroblasts

Cholinergic differentiation of sympathetic neurons—the emergence of diversity at the neurochemical level

Development of the transmitter release machinery—coordinating neuronal differentiation and diversification

Development of electrical membrane properties—differentiation and diversification to be analysed

Development of specific projections between preganglionic and postganglionic neurons—more than a century's problem

Conclusions

Acknowledgements

J. Mol. Biol.

Prog. Neurobiol.

Cell

Neuron

J. Biol. Chem.

Dev. Biol.

Dev. Biol.

Brain Res.

Mech. Dev.

Mech. Dev.

Mech. Dev.

Cell

Neuroscience

Curr. Opin. Neurobiol.

Dev. Biol.

Auton. Neurosci.

J. Biol. Chem.

J. Auton. Nerv. Syst.

Dev. Brain Res.

Cell

J. Biol. Chem.

Trends Neurosci.

TINS

Neuroscience

Neuron

Neuron

J. Biol. Chem.

J. Physiol. (Paris)

TIG

J. Biol. Chem.

Mol. Cell. Neurosci.

Dev. Biol.

J. Auton. Nerv. Syst.

Neuroscience

Neuron

Neuron

Cell

Neuron

Neuron

Neuron

Developmental changes in the transmitter properties of sympathetic neurons that innervate the periosteum

J. Neurosci.

Differential expression of SNAP-25 protein isoforms during divergent vesicle fusion events of neural development

Proc. Natl. Acad. Sci. U. S. A.

Developmental and plasticity-related differential expression of two SNAP-25 isoforms in the rat brain

J. Comp. Neurol.

Neurotrophin-3 promotes the cholinergic differentiation of sympathetic neurons

Proc. Natl. Acad. Sci. U. S. A.

Review lecture. Neurotransmitters and trophic factors in the autonomic nervous system

J. Physiol.

The Wisdom of the Body

Characteristics of phasic and tonic sympathetic ganglion cells of the guinea-pig

J. Physiol.

Ontogenetic appearance and disappearance of tyrosine hydroxylase and catecholamines in the rat embryo

Proc. Natl. Acad. Sci. U. S. A.

Initial development of the noradrenergic phenotype in autonomic neuroblasts of the rat embryo in vivo

Dev. Biol.

Potassium channel mRNA expression in prevertebral and paravertebral sympathetic neurons

Eur. J. Neurosci.

Review
The development of postganglionic sympathetic neurons: coordinating neuronal differentiation and diversification