Trends in Neurosciences
ViewpointParacrine neurotransmission in the CNS: involvement of 5-HT
Section snippets
GABAergic and glutamatergic neurotransmission: examples of synaptic transmission
The most direct way to evaluate synaptic neurotransmission is to measure the time course between synaptic release and the response at a postsynaptic neuron. The binding of neurotransmitters whose receptors are ligand-gated ion channels, such as glutamate9 and GABA (Ref. 10), results in an almost immediate postsynaptic response. Thus, diffusion of released neurotransmitters to receptor sites and the subsequent binding of these neurotransmitters are the rate-limiting factors for the postsynaptic
Architecture of serotonergic nerve terminals
Because 5-HT exerts many of its actions via G-protein coupled receptors, the postsynaptic responses that follow receptor binding are slower than those elicited by the ligand-gated ion channels, and direct electrophysiological approaches to distinguish synaptic and paracrine neurotransmission cannot be used. However, the synaptic morphology and the location and quantity of release sites, receptors and transporters have been characterized in several regions of the brain. Furthermore,
Voltammetrical studies
Early work with carbon-fiber microelectrodes showed that 5-HT could be detected following release elicited by electrical stimulation34. Improvements in the technique led to real-time measurements of its concentration changes35. The sequence of events during detection is shown in Fig. 2. Given that the tip diameter of the carbon-fiber electrode is 10–15 μm, these measurements are of extracellular, rather than synaptic, concentrations. With Nafion-coated electrodes, diffusion through the coating
Quantitative evaluation of elicited release
In order to evaluate the likelihood that 5-HT leaves the synaptic cleft, it is preferable to use a single electrical impulse. Efflux during stimulus trains can be enhanced because of the occupancy of uptake sites and receptor binding sites within the synaptic cleft by previously released neurotransmitter. Furthermore, short trains ensure that release is not modulated by autoreceptor activation38.
In both the DR and SNr, the 5-HT concentration elicited by single stimulation pulses was compared
Paracrine transmission in the brain
As reviewed in this article, 5-HT is emerging as a prominent paracrine neurotransmitter in the brain regions investigated. Surprisingly, paracrine neurotransmission is found in regions where terminals are junctional (SNr) or predominantly nonjunctional (DR). Although the spatial dimensions of the voltammetrical probe preclude direct measurements of synaptic concentrations, voltammetrical measurements nonetheless provide predictive results and conclusions concerning paracrine neurotransmission.
Acknowledgements
The authors’ research was supported by the National Institute of Health (NS 15841).
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