BBB seminar: Bert Sakmann
Local routes revisited: the space and time dependence of the Ca2+ signal for phasic transmitter release at the rat calyx of Held
Bert Sakmann, Nobel Laureate in Physiology or Medicine
Max Planck Institute for Medical Research, Heidelberg, Germany
During the last decade, advances in experimental techniques and quantitative modelling have resulted in the development of the calyx of Held as one of the best preparations to study synaptic transmission. Here, we review some of these advances, including recording simultaneously pre- and postsynaptic currents, measuring the Ca2+ sensitivity of transmitter release, reconstructing the 3D-anatomy at the EM level, and modelling buffered Ca2+ diffusion. An important outcome of these studies has been an improved understanding of the Ca2+ signal that controls phasic transmitter release. We illustrate the spatial and temporal aspects of the three main steps in the presynaptic signalling cascade: Ca2+ influx through a cluster of voltage gated calcium channels, buffered Ca2+ diffusion from the channels to releasable vesicles, and activation of the Ca2+ sensor for release. Particular emphasis is given to how presynaptic Ca2+ buffers affect the Ca2+ signal and thus the time course of the release probability. Since many aspects of the signalling cascade were first conceived at the squid giant presynaptic terminal, we include comparisons to the squid model and revisit some of its implications. While the characteristics of buffered Ca2+ diffusion presented here are based on the calyx of Held, we demonstrate the circumstances under which they may be valid for other nerve terminals at mammalian CNS synapses.
Bollmann JH, Sakmann B. (2005) Control of synaptic strength and timing by the release-site Ca2+ signal. Nature Neurosci 8:426-34.
Satzler K, Sohl LF, Bollmann JH, Borst JG, Frotscher M, Sakmann B, Lubke JH. (2002) Three-dimensional reconstruction of a calyx of Held and its postsynaptic principal neuron in the medial nucleus of the trapezoid body. J Neurosci 22:10567-79.
Meinrenken CJ, Borst JG, Sakmann B. (2002) Calcium secretion coupling at calyx of Held governed by nonuniform channel-vesicle topography. J Neurosci 22:1648-67.
Bollmann JH, Sakmann B, Borst JG. (2000) Calcium sensitivity of glutamate release in a calyx-type terminal. Science 289:953-7.
Wu LG, Borst JG, Sakmann B. (1998) R-type Ca2+ currents evoke transmitter release at a rat central synapse. Proc Natl Acad Sci U S A 95:4720-5.
Borst JG, Sakmann B. (1996) Calcium influx and transmitter release in a fast CNS synapse. Nature 383:431-4.
Host: Espen Hartveit, Department of Biomedicine
|Prof. Bert Sakmann is Head of the Department of Cell Physiology at the Max Planck Institute for Medical Research in Heidelberg, Germany. The overall goal of his research is to elucidate the mechanisms of fast signalling within nerve cells, between nerve cells and of long-term changes in their synaptic coupling. Nerve cells are highly polarized cells with different compartments referred to as dendrites, soma, axon and terminals. For the communication between these compartments electrical signals are used which are encoded as a transient rise in intracellular calcium. To decipher this code and identify the intracellular receivers of calcium transients is one of his aims. Nerve cells communicate with each other via synapses and the elucidation of transmitter release and its postsynaptic action in CNS synapses is the second main theme of his research work. In 1991, Bert Sakmann was awarded the Nobel Prize in Physiology or Medicine together with Erwin Neher for the "discoveries concerning the function of single ion channels in cells" (http://nobelprize.org/medicine/laureates/1991/index.html).|