Erwin Neher

Biophysics of Short-term Synaptic Plasticity (Lecture + Discussion)


Abstract

The term "synaptic plasticity" describes the fact that connection strengths between the neurons of our brain change constantly in a use-dependent manner. These changes occur on many time scales and underly many of the computational capabilities of our brain. Molecular mechanisms for the fast forms, so-called "short-term plasticity" are still a matter of debate.
The "Calyx of Held", a glutamatergic presynaptic terminal in the auditory pathway is large enough that quantitative biophysical techniques, such as voltage clamp, Ca++ fluorimetry and Ca++ uncaging can be applied. Using these experimental tools, we have studied the role of Ca++ and other second messengers in neurotransmitter release and short-term synaptic plasticity (see E. Neher and T. Sakaba, 2008, Neuron 59, 861-872 for review). We found that the concentration of free calcium ([Ca++]i) has at least three roles i) it triggers neurotransmitter release in a highly cooperative fashion ii) it accelerates linearly the recruitment of new releasable synaptic vesicles during ongoing stimulation and iii) it mediates short-term facilitation. Recruitment of vesicles is rate-limiting for neurotransmitter release during sustained high-frequency activity. Therefore, the acceleration of this process by Ca++ has a very important modulatory role. Surprisingly we found that this process is not limited by the availability of vesicles or the assembly of a molecular release machinery. Rather, new vesicles rapidly enter a state in which they can be released by caged Ca++. Another slower step is required to bring them near Ca++-channels, such that they may also be released by short action potentials.


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