Seminars in Neuroscience最新文献

No abstract

Ng-CAM/L1 and Nr-CAM are closely related neural cell adhesion molecules expressed on neurons and Schwann cells. Ng-CAM/L1 is prevalent on axons and is a potent promoter of neurite growth and axonal fasciculation. Although Nr-CAM does not appear to play a major role in these functions, its transient expression in the developing floor plate of the spinal cord is important for guidance of commissural axons. Ng-CAM and Nr-CAM can bind homophilicly and heterophilicly to several adhesion molecules. Different complexes of adhesion molecules are likely to control axonal growth and guidance as a consequence of their differential localizationsin vivo.

The extracellular matrix is a well organized structure with profound effects on the development and the integrity of adherent tissues. Agrin is a component of many matrices, such as the basement membrane of kidney, blood capillaries and the muscle fiber basal lamina, where it is highly concentrated at the neuromuscular junction. During synapse formation agrin is believed to promote differentiation of the postsynaptic muscle fibers and the presynaptic motor neuron. This complex process is, at least in part, based on specific interactions of agrin with other matrix molecules and with membrane-associated or integral membrane proteins of the abutting cells. This review summarizes studies concerning the integration of agrin with other molecules and highlights possible functions of agrin in the synaptic basal lamina and in other matrices.

BEHAB, a gene encoding a hyaluronan binding protein, is expressed only in the central nervous system. BEHAB is almost identical to brevican, but the predicted BEHAB protein is shorter than that of brevican, and does not include glycosaminoglycan addition sites. During brain development BEHAB is expressed at high levels in the proliferative ventricular zone coincident with the peak period of glial cell generation. BEHAB is also expressed during reactive gliosis and in primary glioma. The extracellular protein encoded by BEHAB may play a role in glial cell generation or motility.

Neurotransmitter is released from synaptic terminals by rapid and highly targeted fusion of synaptic vesicles with the presynaptic membrane. Several lines of evidence suggest that the trigger for vesicle fusion is the large increase in internal [Ca²⁺] (up to hundreds of micromolar) achieved within the submicroscopic domain of elevated calcium near open calcium channels. The rapid rise and fall of [Ca²⁺] in this microdomain, together with the fast kinetics of the calcium-triggered fusion machinery, account for the speed of synaptic exocytosis.

No abstract

Ca²⁺signalling in neurones is primarily fast, by influx through voltage- or ligand-gated channels in the surface membrane. The role and mechanisms of Ca release from intracellular stores in central neurones are not as well established as slow metabolic or secretory responses in peripheral tissues or in cardiac e–c coupling. Ca release in neurones produces short-term changes in excitability due to activation of Ca²⁺-gated channels, and less well defined long-term changes in excitability or synaptic strength. Neither mode of Ca release, via IP3 or CICR, is easily demonstrated physiologically in neurones and the role and mechanisms are reviewed with reference to peripheral tissues, morphological specializations and properties of intracellular Ca channels. It can be speculated that IP3 provides a diffusible signal that can produce Ca release in particular regions of the cell, near the nucleus for coupling to gene activation, in specific areas of the cytosol to modify structural proteins, and to activate Ca-dependent kinases, processes that might produce changes in excitability. Evidence of an inhibitory action of Ca²⁺influx on IP3 evoked release is presented. The role of CICR appears to be simply local amplification of membrane Ca signals, originating with Ca influx during action potentials, Ca-permeable ligand-gated channels and possibly also with IP3 evoked release. Because of the restricted diffusion of Ca ions, the amplification may depend on local structural specializations.

Many hormones, growth factors and neurotransmitters stimulate the production of inositol 1,4,5-trisphosphate evoking the release of calcium from intracellular stores. The depletion of these intracellular calcium stores subsequently activates a voltage-independent plasma membrane calcium influx in many cell types. This store-operated calcium influx is essential for generating prolonged cytosolic calcium signals and for refilling the intracellular calcium stores. Recent studies suggest that the store-operated calcium channels may be encoded by thetrpfamily of genes, which show structural homology to voltage-operated channels. Ankyrin-like repeats encoded bytrpmay be involved in regulating the channel by a direct interaction with the inositol 1,4,5-trisphosphate receptor on the intracellular calcium stores.

The corticostriatal projection has a major function in the control of movements. Alterations of the release of glutamate from corticostriatal terminals have been implicated in disorders of the basal ganglia such as Parkinson's disease and Huntington's chorea. The long-term regulation of corticostriatal transmission might require the participation of different forms of striatal synaptic plasticity. In physiological condition (1·2 mM external magnesium) the tetanic stimulation of cortical afferents produces a LTD of excitatory synaptic potentials recorded in the striatum. When the external magnesium is omitted, this tetanus induces LTP. NMDA receptor antagonists prevent the induction of LTP, but not the generation of LTD. LTD is blocked either by BAPTA and EGTA or by thapsigargin suggesting that a rise of intracellular Ca²⁺is required for this form of synaptic plasticity. Nifedipine is also able to prevent LTD indicating that high voltage-activated (HVA) Ca²⁺channels of the L-type are implicated in the formation of LTD. Moreover, LTD is blocked by inhibitors of Ca²⁺-dependent kinases suggesting that a rise in internal Ca²⁺is a crucial step for the subsequent activation of a second messenger cascade. Although both striatal LTD and LTP seem to require an increase in intracellular Ca²⁺concentration, this change is probably arising from different sources.

For many years the importance of internal calcium stores (ICSs) in excitation–contraction coupling and endocrine function has been well recognized. With the discovery of ICSs in the CNS, evidence has accumulated regarding their role in neuronal function, and in particular, synaptic plasticity. In this review we focus on the involvement of ICSs in synaptic plasticity in the hippocampus.