Seminars in Neuroscience最新文献

An understanding of the neurobiological substrates of brain dysfunction associated with substance abuse is essential for the development of effective treatments for this disorder. Noninvasive brain imaging provides a powerful approach to obtain the relevant information for it permits thein vivoassessment of brain function under different conditions that characterize various stages of an addictive cycle.

The development of spinal nerve segmentation in higher vertebrate embryos provides a convenient experimental system for the analysis of axon guidance mechanisms. We review evidence from chick embryo experiments that segmentation of motor and sensory axons results from a combination of contact repulsion of axon growth cones by posterior somite cells and chemoattraction of growth cones by anterior cells. We also review progress in identifying the underlying molecular mechanisms in this system, and suggest a prominent role for carbohydrate groups in mediating growth cone repulsion.

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It is widely accepted that astroglia plays an important role in the regulation of neural pattern formation, for example by guiding migrating neuroblasts and growth cones or by designing transient tissue boundaries. In this context, the tenascin-C glycoproteins of the extracellular matrix have attracted increased attention, because they are selectively expressed by glial lineages in the brain and exert both stimulatory and inhibitory effects on CNS neurons. Several lines of evidence suggest that these properties are encoded by distinct molecular domains. This concept has been probed by the use of recombinant proteins in various in-vitro assays. The present review summarizes these studies which show that several functions of tenascin-C can be reproduced with isolated, defined segments of the molecule.

A particularly intriguing role in communication within the nervous system is played by glycosyl phosphatidylinositol (GPI)-anchored glycoproteins. Although our understanding of how neuronal GPI-linked molecules transduce signals is still in its infancy, it is now possible to assemble a tentative model to describe their functioning. Shared features of these otherwise diverse receptors will be outlined, with particular emphasis given to the exclusively GPI-anchored contactin/F11 subgroup of the immunoglobulin superfamily. Contactin/F11 itself, with five extracellular ligands and an intracellular pathway involving Fyn, serves to illustrate the wide range of signalling possible through this group of receptors.

The neuromuscular system provides an ideal model for the elucidation of the molecular mechanisms involved in neuron–target cell interactions, and the development and maintenance of synaptic connections. Many processes important in neuronal development occur during the formation of neuromuscular connections and synaptogenesis. These include the process of pathfinding by motor neurons, selection of target tissues and synaptogenesis. In the present paper we discuss the molecular mechanisms that probably play a role in the development of skeletal muscle innervation, with particular emphasis on cell adhesion molecules (CAMs).

Plasminogen activators are extracellular serine proteases, which are actively secreted by developing and regenerating neurons. These molecules, as discussed in this review, have been implicated in cell migration, axonal growth, growth factor activation, and synaptic remodeling associated with learning. Secreted plasminogen activators not only bind to their specific cell surface receptors, where they retain full proteolytic activity, but they also associate with extracellular matrix molecules including fibronectin and laminin. Plasminogen activator association with specific matrix proteins may target these proteins for degradation, altering the matrix composition and leading to intracellular signaling and influencing cell differentiation. The secreted plasminogen activators can bring about the degradation of matrix molecules either directly, or indirectly via the formation of plasmin.