Pattern of presynaptic nerve activity can determine the type of neurotransmitter regulating a postsynaptic event

The mammalian superior cervical ganglion has been the classical preparation for studying cholinergic transmission between neurones. Recently, however, evidence has been presented showing that, in addition to the postsynaptic changes mediated via nicotinic and muscarinic receptors, there is a non-cholinergic component to transmission in this ganglion, as in frog paravertebral ganglia. In the rabbit superior cervical ganglion, Ashe and Libet recorded a late, slow excitatory postsynaptic potential in response to preganglionic nerve stimulation in the presence of nicotinic and muscarinic antagonists. We have found, in the rat superior cervical ganglion, that a postsynaptic biochemical consequence of preganglionic nerve stimulation, namely the acute activation of tyrosine 3-monooxygenase (tyrosine hydroxylase, TH; EC 1.14.16.2), is mediated in part by acetylcholine and in part by a non-cholinergic neurotransmitter. The regulation of this enzyme activity is of particular interest because it catalyses the rate-limiting step in the biosynthesis of the postganglionic neurotransmitter, noradrenaline. In the present paper, we report that the relative importance of cholinergic and non-cholinergic transmission in the regulation of TH activity varies with the pattern of electrical stimulation of the preganglionic nerve trunk

Neurotrophic factors and their receptors

Development of the nervous system depends on signals that instruct neurons when to divide, differentiate, survive, or die. There are now two known distinct classes of factors noted for their neurotrophic activities-the family of factors collectively known as the neurotrophins, and ciliary neurotrophic factor. Neurotrophin-mediated signaling pathways initiate by autophosphorylation of Trk receptors, which are receptor tyrosine kinases similar to the receptors for traditional growth factors such as fibroblast growth factor. In contrast, ciliary neurotrophic factor employs a receptor system that shares components with the receptor complexes for a subclass of distantly related hematopoietic cytokines. These two distinct classes of neurotrophic factors, utilizing distinct signaling pathways, can interact to effect the growth and differentiation of neuronal progenitors during neuropoiesis in a way analogous to that exhibited by the cytokines during hematopoiesis

Neurotrophic factor receptors: Just like other growth factor and cytokine receptors?

As the actions of neurotrophic factors appear so strikingly different from those of growth factors and cytokines operating elsewhere in the body, it was long thought that neurotrophic factors might in some way be fundamentally different from traditional growth factors and cytokines. Recent advances in the understanding of the structure of the receptors for neurotrophic factors reveals them to be much more like the receptors used by other cytokines and growth factors than was perhaps first anticipated. These findings suggest that neurotrophic factors display distinctive actions not because they utilize novel receptor systems, but rather because they activate these receptors in neurons

The roles of cyclin-dependent kinase 5 in dendtrite and synapse development

Since the isolation of cyclin-dependent kinase 5 (Cdk5), this proline-directed serine/threonine kinase has been demonstrated as an important regulator of neuronal migration, neuronal survival and synaptic functions. Recently, a number of players implicated in dendrite and synapse development have been identified as Cdk5 substrates. Neurite extension, synapse and spine maturation are all modulated by a myriad of extracellular guidance cues or trophic factors. Cdk5 was recently demonstrated to regulate signaling downstream of some of these extracellular factors, in addition to modulating Rho GTPase activity, which regulates cytoskeletal dynamics. In this communication, we summarize our existing knowledge on the pathways and mechanisms through which Cdk5 affects dendrite, synapse and spine development. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Receptors and signaling pathways of ciliary neurotrophic factor and the neurotrophins

In this article, we review the receptor systems that two distinct classes of neurotrophic factors, the neurotrophins (NGF, BDNF, NT-3 and NT-4/5) and CNTF, utilize to act on neurons. Both of these receptor systems are analogous to receptor systems outside of the nervous system. The neurotrophins act through a family of receptor tyrosine kinases (the Trks) very similar to those used by traditional growth factors (such as FGF and PDGF), whereas the trimeric CNTF receptor complex shares receptor components with a family of cytokines (including LIF, OSM and IL6). Although the neurotrophin and CNTF receptor systems differ drastically, they display certain parallels. Both the Trk receptors and the CNTF receptor complex depend on ligand-induced dimerization of signal transducing receptor components to activate signaling. Furthermore, both the neurotrophin receptors and the CNTF receptor complex do not appear to have any unique signaling capabilities that distinguishes them as 'neurotrophic factors', rather, it is the largely restricted expression of their receptor components to the nervous system that underlies their discovery as neuronal survival and differentiative factors

The neurotrophins and CNTF: Two families of collaborative neurotrophic factors

Because the actions of neurotrophic factors appear distinct from those of traditional growth factors and cytokines, it was long assumed that the neurotrophic factors utilized receptors and signaling systems fundamentally different from those used by growth factors operating elsewhere in the body. Recent advances in the understanding of the structure of the receptors for neurotrophic factors have unexpectedly revealed that they are in fact similar to the receptors used by the traditional growth factors and cytokines. The expression of the receptors for the neurotrophic factors is exclusively or predominantly in the nervous system; activation of these receptors in the context of the neuron allows these factors to display distinctive actions. While the precise roles of the neurotrophic factors and their therapeutic potential in various disease slates still remain to be elucidated, this review describes studies on their receptor systems, their notable biological activities in the nervous system, and recent insights provided by targeted gene disruptions

Long-term regulation of tyrosine hydroxylase activity in the superior cervical ganglion in organ culture: Effects of nerve stimulation and dexamethasone

The rat superior cervical ganglion was stimulated in vitro via its preganglionic trunk and then maintained in organ culture for 2-3 days. Following nerve stimulation, the specific activity of tyrosine hydroxylase (TH) increased with a lag period of at least 12 h, and this increased enzyme activity was maintained throughout the culture period. The magnitude of the increase in TH activity depended on the frequency and duration of preganglionic nerve stimulation. This transsynaptic increase in enzyme activity could be completely blocked by the nicotinic antagonist, hexamethonium. The synthetic glucocorticoid dexamethasone, at concentrations above 1 nM, increased TH activity in unstimulated ganglia with a lag period of at least 24 h. The increase in enzyme activity produced by dexamethasone was not affected by nicotinic antagonists or by prior decentralization of the superior cervical ganglion, in contrast to the findings of previous workers. These data indicate that dexamethasone can stimulate ganglionic TH activity in the absence of cholinergic stimulation. In addition, experiments combining dexamethasone with nerve stimulation demonstrate that the steroid can potentiate the effects on TH activity of brief periods of nerve stimulation

Ciliary neurotrophic factor and its receptor complex

Ciliary neurotrophic factor (CNTF), originally identified for its ability to promote survival of neurons of the ciliary ganglion, is now known to have additional survival and differentiative actions on cells of the nervous system. CNTF is, however, unrelated in structure to the nerve growth factor family of neurotrophic factors. Instead, CNTF is distantly related to, and in fact shares receptor components with, a number of hemopoietic cytokines. This review focuses on the biological actions of CNTF, the shared and unique features of the CNTF receptor complex and signaling pathways, and the distribution of CNTF and its receptor during development, in the adult and in response to injury