Extra synaptic

Parkinsonism is unique among diseases of the CNS, in that it results from the known loss of a particular NT, i.e. DA, resulting from the degeneration of a particular pathway, the nigrostriatal. Dopamine also has a relatively limited distribution in the brain and few peripheral effects. It should therefore be amenable to therapy based on augmenting its function. Also since the role of DA appears to be to maintain a tonic inhibitory control on GABA output pathways from the striatum, possibly in part by an extra synaptic action (Chapter 6), it may not be necessary for it to be released physiologically from nerve terminals. Thus it may be adequate to just provide DA extracellularly. 

Ascaris somatic muscle cells also possess inhibitory synaptic and extra-synaptic GABA-gated Cl channels (Martin, 1980). Activation of these... 

Balfour DJK, Ridley DL (2000) The effects of nicotine on neural pathways implicated in depression a factor in nicotine addiction Pharmacol Biochem Behav 66 79-85 Balfour DJK, Birrell CE, Moran RJ, Benwell MEM (1996) Effects of acute D-CPPene on mesoac-cumbens dopamine responses to nicotine in the rat. Eur J Pharmacol 316 153-156 Balfour DJK, Wright AE, Benwell MEM, BirreU CE (2000) The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence. Behav Brain Res 113 73-83... 

Barnard, E.A., Lai, J., Pizzey, J. (1984). Synaptic and extra-synaptic forms of acetylcholinesterase in skeletal muscles variation with fiber type and functional considerations. In... 

Interest in the PGs has recently reverted to their precursor arachidonic acid (AA), which seems to be able to act intracellulary as a second messenger, and also extra-cellularly. In this latter mode it may play a part in LTP. It is known that AA produces a long-lasting enhancement of synaptic transmission in the hippocampus that resembles LTP and in fact activation of NMDA receptors leads to the release of AA by phospholipase A2 (see Dumuis et al. 1988) and inhibition of this enzyme prevents the induction of LTP. AA has also been shown to block the uptake of glutamate (see Williams and Bliss 1989) which would potentiate its effects on NMDA receptors. This would not only prolong LTP but also cause neurotoxicity. 

Reduce destruction. This may be achieved by blocking the neuronal or glial uptake (3a) of the NT or its extra- (3b) or intraneuronal metabolism (3c). Its success depends on there still being an adequate, even if reduced, release of the NT, and the protected NT being able to work postsynaptically and not stimulate autoreceptors to reduce the synaptic release of the endogenous NT even further. If the uptake sites are outside the synapse then the protected NT may not easily gain access to the receptors located postsynaptically. 

The technical problems involved with any attempt to use analogously systematic research approaches to a potential transmitter in the central nervous system are great. Peripheral synapses can be isolated by microdissection, they can remain functional in an isolated profusion experimental situation for hours, and their activation can be manifested by clearly defined and measurable phenomena (such as the miniature end-plate potential or the contraction of smooth muscle). The central nervous system has little in the way of focal synaptic regions. The dendrites and the cell bodies of central neurons are densely covered with synapses, many of which may be of a chemically heterogenous nature. In addition, the extra-neuronal space is packed with a tangle of glia, closely approximating the membranous surfaces of nerve cells and possibly intrinsically important to their function. This makes the isolated, chemical manipulation of central synapses extremely difficult. (Mandell and Spooner 1968, p. 1443)... 

As the action potential sweeps into presynaptic region, there is a rapid influx of calcium from the extra cellular fluid into a qtecialized area of the presynaptic terminus termed the maptic knob. Via the process of exocytosis, specific neurotransmitters are then released from synaptic vesicles into the synaptic gap. The neurotransmitters drfiuse across the synaptic gap and specifically bind to specialized receptor sites cn the dendrite of the post aptic neurcn. 

The FFBP distinguishes itself by the presence of one or more hidden layers, whose computation nodes are correspondingly called hidden neurons of hidden units. The function of hidden neurons is to intervene between the external input and the network output in some useful manner. By adding one or more hidden layers, the network is enabled to extract higher order statistics. In a rather loose sense, the network acquires a global perspective despite its local connectivity due to the extra set of synaptic connections and the extra dimension of NN interconnections (Hagan and Menhaj, 1994). Figure 1 depicts die structure of a FFBP neural network. 

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