Synaptic transmission model

Some neurons can fire several hundred times per second, secreting neurotransmitter each time. Synapses are remarkable secretion machines destined to undergo millions of repeated exocytic cycles in their lifetime. So how does this process work so fast and so efficiently Answers have gradually emerged from the work of many different laboratories and model systems [73, 74]. An exhaustive description is beyond the scope of this chapter, but a summary of key events and specializations of the synaptic vesicle cycle is useful. This will show how synaptic transmission is optimized spatially and biochemically (see also Chs 6,10 and 22). 

Finally, it is tempting to speculate that in SC and postinfectious forms of TS the functional activity of the MSP neurons of the matrix is differentially impaired as a result of the autoimmune response. Indeed, preliminary data suggest that either bilateral striatal infusion into rats of antineuronal antibodies from TS patients or the immunization of mice with rat striatal homogenates may produce animal models of TS complete with stereotypical movements and audible vocalizations (Hallett et al., 2000 Hoffman and Lipkin, 2000). One plausible hypothesis is that the antineural antibodies found in a subset of TS patients may modulate synaptic transmission and alter the balance between the striosomal and matrisomal compartments of the striatum (Leckman and Riddle, 2000). 

R12,495AA on afferent-evoked spinal synaptic transmission in vitro and on models of acute and chronic inflammation in the rat, J. Pharmacol. Exp. Ther. 2000, 294, 876-883. 

The neuraminidases together with gangliosides have been localized in the nerve ending structures (6, 7 ). Theoretically the sialylation and desialylation cycle may mediate a cyclic reaction at a very important locale in a nerve synaptic structure. This hypothetical involvement of sialic acid metabolism in synaptic transmission has gained support from several studies which have suggested a synaptic localization of the glycosyltransferases (8, 9,10,11) and from proposed theoretical models in which the sialo-glycolipids are considered an important constituent in the functional units of neuronal membranes (12,13,14). 

In contractile experiments the time from the stimulation of the nerve to the CMAP recorded in muscle provides an estimate of NCV. The length of the nerve from the stimulating electrode to the muscle can simply be measured and divided by the time. However, the time recorded in this way includes the delay for synaptic transmission, which may be increased in models with synaptic defects. If this is a concern or if the only parameter desired is NCV, then the measurement can be obtained non-invasively with a relatively simple setup (e.g., (3)). Using the sciatic nerve, NCV can be calculated by measuring the latency of compound motor action potentials recorded in the muscle of a rear paw. Action potentials are produced by subcutaneous stimulation at two separate sites proximal stimulation at the sciatic notch and distally at the ankle. NCV is then calculated by using the two latencies and conduction distance. Decreases in nerve conduction velocity most often reflect defects in myelination, but may also be the result of changes in internodal distance, decreased axon diameters, or altered excitability. 

One of the major problems in thinking about dopamine neurotransmission is the number of features which do not fit into the textbook model of classical synaptic transmission, based on the neuromuscular junction. These include an extremely wide divergence of release sites of a single axon, extrasynaptic location of receptors, termination of neurotransmitter action by diffusion and uptake from extrasynaptic sites, and significant overflow of neurotransmitter from the synaptic cleft into the extracellular space. 

The availability of genetically modified mice has advanced our understanding of several neurodegenerative processes. Cellular neurobiology experiments have informed us about mechanisms of neuronal dysfunction in AD and PD mouse models. For instance, recent studies have identified that synaptic transmission is one of the earliest events in the cognitive abnormalities that characterize AD and PD. The integration of this information with data-based circuits modeling, in which neuronal electrical properties, synaptic transmission parameters, and brain oscillations can now be evaluated and it has been recently addressed in PD and AD. 

It must be conceded that these tentative models for learning and memory are concerned with neural functions far from those presumed to be involved with the interaction of serotonin or an analogous hallucinogen with its receptor site. However, the fact that the hallucinogenically induced state represents a novel learning experience and at times results in an alteration in behavior patterns indicates that the processes effected by hallucinogens (synaptic transmission) may indeed have some influence on... 

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