Neurotransmitters single neurons

Harris-Warrick R. (2005). Synaptic chemistry in single neurons GABA is identified as an inhibitory neurotransmitter. J. Neurophysiol. 93, 3029-31. 

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... 

Important non-DNA application areas for precapillary derivatiation with LIF detection include the determination of amino acids and amines in cerebrospinal fluid to distinguish disease states such as Alzheimer s disease and leukemia from the normal population. In vivo monitoring of microdialysates from the brain of living animals has been employed for the determination neuropeptides, amphetamine, neurotransmitters, and amino acids. The contents of single neurons and red blood cells have been studied as well. 

Lapainis, T., Scanlan, C., Rubakhin, S. S., and Sweedler, J. V., A multichannel native fluorescence detection system for capiUary electrophoretic analysis of neurotransmitters in single neurons. Anal. Bioanal. Chem., 387, 97-105, 2007. 

Despite the predominant use of fluorescence and/or patch clamp techniques in single cell measurements, there has been a steady increase in the demand for new electroanalytical tools applicable to single cell studies [4]. Traditionally, such methods have been confined to the development and production of hand crafted sensors including the aforementioned glass capillaries [1-3] for patch clamping, as well as conical microelectrodes for scanning electrochemical microscopy (SECM) [5, 6] and carbon fiber microelectrodes to measure for example, the release of neurotransmitter from single neurons [7, 8]. 

The release of neurotransmitters from neuronal terminals in the brain can be viewed as a quantal event. When an action potential arrives at a nerve terminal, a finite number of synaptic vesicles fuse with the terminal membrane and release their contents into the extracellular space. This release event occurs very rapidly studies of exocytotic events in single isolated cells show that they occur on a sub-miUisecond timescale [34, 35]. Furthermore, the event is spatially discrete, since the nerve terminals themselves have dimensions of just a few hundred nanometers [36, 37). With this description in mind, it is reasonable to regard each nerve terminal as... 

Figure 1.3 Some possible basic neurotransmitter-synaptic arrangements for the excitation and inhibition of different neurons, (a) The single NT activates neuron B and inhibits neuron C by being able to activate both excitatory and inhibitory receptors or, more probably, acting on one receptor linked to both events. There is potential, however, for the NT to activate any inhibitory receptors that may be on B or excitatory receptors on C. (b) The same NT is used as in (a) but the excitatory receptors are now only on dendrites and separated from the inhibitory receptors only on the soma. There is less chance of unwanted mixed effects, (c) Neuron A releases distinct excitatory and inhibitory NTs from its two terminals each acting on specific and morphologically separated receptors. But this depends on a neuron being able to release two NTs. (d) Neuron A releases the same NT from both terminals. It directly excites B but inhibits C through activating an inhibitory interneuron (I) which releases an inhibitory NT onto specific receptors on C. This last scheme (d) is clearly more functional and is widely used...

Almost invariably, a neuron is genetically programmed to synthesize and release only a single type of neurotransmitter. Therefore, a given synapse is either always excitatory or always inhibitory. Once a neurotransmitter has bound to its receptor on the postsynaptic neuron and has caused its effect, it is important to inactivate or remove it from the synapse in order to prevent its continuing activity indefinitely. Several mechanisms to carry this out have been identified ... 

Synapses between the autonomic postganglionic neuron and effector tissue — the neuroeffector junction — differ greatly from the neuron-to-neuron synapses discussed previously in Chapter 5 (see Table 9.1). The postganglionic fibers in the ANS do not terminate in a single swelling like the synaptic knob, nor do they synapse directly with the cells of a tissue. Instead, the axon terminals branch and contain multiple swellings called varicosities that lie across the surface of the tissue. When the neuron is stimulated, these varicosities release neurotransmitter over a large surface area of the effector tissue. This diffuse release of the neurotransmitter affects many tissue cells simultaneously. Furthermore, cardiac muscle and most smooth muscle have gap junctions between cells. These specialized intercellular communications... 

One characteristic of regulated exocytosis is the ability to store secretory vesicles in a reserve pool for utilization upon stimulation. In the presynaptic terminal, this principle is expanded to define multiple pools of synaptic vesicles a ready releasable pool, a recycled synaptic vesicle pool and a larger reserve pool. This reserve pool assures that neurotransmitter is available for release in response to even the highest physiological demands. Neurons can fire so many times per minute because synaptic vesicles from the ready releasable pool at a given synapse undergo exocytosis in response to a single action potential. 

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