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A biophysical dissection of neurotransmitter release at a glutamatergic synapse
Author(s) -
Neher Erwin
Publication year - 2008
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2008.01.017
Subject(s) - nobel laureate , neuroscience , synapse , biophysics , cognitive science , chemistry , biology , philosophy , psychology , linguistics , poetry
A BIOPHYSICAL DISSECTION OF NEUROTRANSMITTER RELEASE AT A GLUTAMATERGIC SYNAPSE Erwin Neher 1991 Nobel Laureate in Physiology or Medicine and Max Planck Institute for Biophysical Chemistry, Department of Membrane Biophysics, 37077 Goettingen, Germany The unique capabilities of our brain as an information processor are critically dependent on the correct function of some 10 billions of neurons, each of which is connected to about 10 000 other neurons by way of synapses. Unlike in electronic computers these connections are not rigid but adapt their coupling strengths in response to the information flow in the system e a phenomenon called synaptic plasticity. A dissection of the process of synaptic transmission as well as of the mechanisms underlying plasticity is essential for understanding some of the major neurological diseases. It has been known since the early fifties, that synaptic transmission is initiated by the release of a signalling substance, the neurotransmitter, from the presynaptic neuron. This, in turn, is triggered by an influx of Calcium ions (Ca) into the nerve terminal. The neurotransmitter, once liberated, induces an increase in the conductance of the postsynaptic membrane. When synaptic strength changes during ‘plasticity‘ this can be a consequence of changes in any of the steps of this complicated process. Unfortunately, most nerve terminals are very small and not readily accessible to detailed investigation, such that usually it is very difficult to assign a given change to one of these molecular mechansims. Quite recently, however, it was discovered that a specialized synapse in the auditory pathway, the ‘Calyx of Held‘, has presynaptic terminals, which are large enough that quantitative biophysical techniques can be applied. Particularly, the postsynaptic current can be measured precisely, while the presynaptic calcium concentration ([Ca]) can be increased or decreased e either by opening and closing of Ca channels or by releasing Ca from a chemically caged form by photolysis. Furthermore, [Ca] can be measured by introducing fluorescent Ca indicators into the terminal. Using these experimental possibilities, we have studied the role of Ca and other second messengers in short-term changes of synaptic strength. We found that there are two steps, which are strongly modulated: i) action potential waveform and Ca influx is modulated in multiple ways by second messengers ii) during ongoing activity new synaptic vesicles have to be recruited, to replace those that have undergone exocytosis. This step of recruitment is also modulated strongly by [Ca], cAMP and other second messengers. The release process itself e although steeply dependent on [Ca] e is relatively immune to other forms of modulation.