Synaptic terminal

FIGURE 17.8 (a) Rapid axonal transport along microtnbnles permits the exchange of material between the synaptic terminal and the body of the nerve cell, (b) Vesicles, mnltivesicn-lar bodies, and mitochondria are carried throngh the axon by this mechanism. 

Helfert, RH, Juiz, JM, Bledsoe, SC, Bonneau, JM, Wenthold, RJ and Altschuler, RA (1992) Patterns of glutamate, glycine and GABA immunolabelling in four synaptic terminal classes in the lateral superior olive of the guinea pig. J. Comp. Neurol. 323 305-325. 

The aforementioned results are consistent with the view that the rat brain PCP/"sigma opiate" high-affinity receptor is associated with the voltage-regulated, non inactivating K channels in the pre-synaptic terminals. Thus, we reasoned that the elucidation of the molecular composition of this PCP "receptor" might provide direct information about the subunit composition of these K channels. 

FIGURE 5.40 Schematic of the dendritic architecture of a neuron. The electrical signal is transferred in a convergent manner from the dendrites toward the axon, where it diverges to the synaptic terminals. 

Neurons constitute the most striking example of membrane polarization. A single neuron typically maintains thousands of discrete, functional microdomains, each with a distinctive protein complement, location and lifetime. Synaptic terminals are highly specialized for the vesicle cycling that underlies neurotransmitter release and neurotrophin uptake. The intracellular trafficking of a specialized type of transport vesicles in the presynaptic terminal, known as synaptic vesicles, underlies the ability of neurons to receive, process and transmit information. The axonal plasma membrane is specialized for transmission of the action potential, whereas the plasma... 

Vesicular proteins and lipids that are destined for the plasma membrane leave the TGN sorting station continuously. Incorporation into the plasma membrane is typically targeted to a particular membrane domain (dendrite, axon, presynaptic, postsynaptic membrane, etc.) but may or may not be triggered by extracellular stimuli. Exocytosis is the eukaryotic cellular process defined as the fusion of the vesicular membrane with the plasma membrane, leading to continuity between the intravesicular space and the extracellular space. Exocytosis carries out two main functions it provides membrane proteins and lipids from the vesicle membrane to the plasma membrane and releases the soluble contents of the lumen (proteins, peptides, etc.) to the extracellular milieu. Historically, exocytosis has been subdivided into constitutive and regulated (Fig. 9-6), where release of classical neurotransmitters at the synaptic terminal is a special case of regulated secretion [54]. 

Neuropeptide receptors are not confined to synaptic regions. Peptidergic neurotransmission often operates on a slower time scale than conventional neurotransmitters, so it is not surprising that peptide receptors are often localized at a distance from the synapse. For example, although some substance P terminals contact membranes loaded with substance P receptor, only a small fraction of the substance P receptor-laden membrane is apposed to synaptic terminals. Substance P may diffuse a considerable distance from its release site and still find a receptor with which it can interact [21]. 

The activity of the malate-aspartate shuttle increases during development in parallel with synaptogenesis, which is consistent with the high activity and importance of this shuttle in neurons and synaptic terminals. Evidence of highly regulated malate-aspartate shuttle in adult human brain has been documented [73 and references therein]. 

McKenna,M. C.,Stevenson,J. H.,Huang,X. etal. Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals. Neurochem. Int. 37 229-241, 2000. 

McKenna, M. C., Tildon, J. T., Stevenson, J. H. Jr etal. Regulation of energy metabolism in synaptic terminals and cultured rat brain astrocytes differences revealed using aminooxyacetate. Dev. Neurosci. 15 320-329,1993. 

Other drugs, like GHB and Rohypnol , can interact directly with the neurotransmitter receptors to either enhance or block the effects of the brain s own neurotransmitters. Still other drugs can alter the metabolic breakdown or clearance of certain neurotransmitters after they are released from the synaptic terminal, thereby altering how long the neurotransmitter affects the activity of other nearby neurons. 

Chemical messengers, or neurotransmitters, are normally released when an action potential reaches the synaptic terminals. This process is entirely Ca2+-dependent. Intracellular Ca2+ causes movement of neurotransmitter-containing synaptic vesicles toward the membrane. Removal of Ca2+ will prevent this process, preventing neurotransmitter release even if an action potential arrives. 

Indirect mechanisms Nicotine has indirect effects on monoamine systems. A considerable amount of research has examined the relationships between nicotine and dopamine activity in the brain, in light of dopamine s role in reinforcement and nicotine s addictive properties. Nicotine increases dopamine turnover in the striatum and cerebral cortex (Clarke and Reuben 1996 Tani et al. 1997 Nanri et al. 1998). It also increases burst activity in dopamine neurons of the ventral tegmental area (VTA), a primary source of dopamine to the forebrain (Nisell et al. 1995 Fisher et al. 1998). Such a firing pattern in the VTA is associated with processes of reinforcement, learning, and cognitive activity. Nicotine actions on dopaminergic neurons occur at both somatodendritic sites and synaptic terminals. Further, both systemic nicotine and direct administration into the VTA increase dopamine release in the nucleus ac-... 

Reserpine blocks vesicular storage of monoamines, prolonging their presence in cytoplasm. There they are degraded by MAO, leading to a depletion of monoamines in synaptic terminals of central and peripheral neurons, so that little or no neurotransmitter is released when the neuron depolarizes (Oates 1996). Reversal of this process requires synthesis of new vesicles, which occurs over a period of days to weeks after discontinuation of the drug. 

Intracerebral injections of ibotenic acid produce cell loss in several cerebral areas, including the striatum, the hippocampus, substantia nigra, and piriform cortex (Schwarcz et al. 1979). This degeneration is limited to the site of injection and does not affect axons, passage, or synaptic terminals originating in other areas. 

Gylys KH, Fein JA, Tan AM, Cole CM. 2003. Apolipopro-tein E enhances uptake of soluble but not aggregated amyloid-P protein into synaptic terminals. J Neurochem... 

All botulin neurotoxins act in a similar way. They only differ in the amino-acid sequence of some protein parts (Prabakaran et al., 2001). Botulism symptoms are provoked both by oral ingestion and parenteral injection. Botulin toxin is not inactivated by enzymes present in the gastrointestinal tracts. Foodborne BoNT penetrates the intestinal barrier, presumably due to transcytosis. It is then transported to neuromuscular junctions within the bloodstream and blocks the secretion of the neurotransmitter acetylcholine. This results in muscle limpness and palsy caused by selective hydrolysis of soluble A-ethylmalemide-sensitive factor activating (SNARE) proteins which participate in fusion of synaptic vesicles with presynaptic plasma membrane. SNARE proteins include vesicle-associated membrane protein (VAMP), synaptobrevin, syntaxin, and synaptosomal associated protein of 25 kDa (SNAP-25). Their degradation is responsible for neuromuscular palsy due to blocks in acetylcholine transmission from synaptic terminals. In humans, palsy caused by BoNT/A lasts four to six months. 

Figure 21.1 A schematic drawing of a synapse. The synaptic terminal is shown activated. Synaptic vesicles are fusing with the presynaptic membrane and releasing a neurotransmitter that diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane. This triggers a new nerve impulse. (Redrawn from D. Voet and J. G. Voet, Biochemistry, 3rd edn, 2004. Donald and Judith G. Voet. Reprinted with permission of John Wiley and Sons, Inc.)...

Above we noted that the fusion of synaptic vesicles or secretory granules with the plasma membrane of the synaptic terminal was caused by the arrival of an electrical signal flowing from the cell body down the axon. What is the nature of this electrical signal ... 

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