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The Journal of Neuroscience, June 28, 2006, 26(26):7071-7081; doi:10.1523/JNEUROSCI.0946-06.2006

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Cellular/Molecular
Main Determinants of Presynaptic Ca²⁺ Dynamics at Individual Mossy Fiber–CA3 Pyramidal Cell Synapses

Ricardo Scott and Dmitri A. Rusakov

Institute of Neurology, University College London, London WC1N 3BG, United Kingdom

Correspondence should be addressed to Dmitri A. Rusakov, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK. Email: d.rusakov{at}ion.ucl.ac.uk

Synaptic transmission between hippocampal mossy fibers (MFs) and CA3 pyramidal cells exhibits remarkable use-dependent plasticity. The underlying presynaptic mechanisms, however, remain poorly understood. Here, we have used fluorescent Ca²⁺ indicators Fluo-4, Fluo-5F, and Oregon Green BAPTA-1 to investigate Ca²⁺ dynamics in individual giant MF boutons (MFBs) in area CA3 traced from the somata of granule cells held in whole-cell mode. In an individual MFB, a single action potential induces a brief peak of free Ca²⁺ (estimated in the range of 8–9 µM) followed by an elevation to 320 nM, which slowly decays to its resting level of 110 nM. Changes in the somatic membrane potential influence presynaptic Ca²⁺ entry at proximal MFBs in the hilus. This influence decays with distance along the axon, with a length constant of 200 µm. In giant MFBs in CA3, progressive saturation of endogenous Ca²⁺ buffers during repetitive spiking amplifies rapid Ca²⁺ peaks and the residual Ca²⁺ severalfold, suggesting a causal link to synaptic facilitation. We find that internal Ca²⁺ stores contribute to maintaining the low resting Ca²⁺ providing 22% of the buffering/extrusion capacity of giant MFBs. Rapid Ca²⁺ release from stores represents up to 20% of the presynaptic Ca²⁺ transient evoked by a brief train of action potentials. The results identify the main components of presynaptic Ca²⁺ dynamics at this important cortical synapse.

Key words: synaptic transmission; synaptic plasticity; presynaptic regulation; calcium; CA3; hippocampus

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Received Nov. 21, 2005; revised May 24, 2006; accepted May 24, 2006.

Correspondence should be addressed to Dmitri A. Rusakov, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK. Email: d.rusakov{at}ion.ucl.ac.uk

This article has been cited by other articles:

				L. P. Savtchenko and D. A. Rusakov The optimal height of the synaptic cleft PNAS, February 6, 2007; 104(6): 1823 - 1828. [Abstract] [Full Text] [PDF]

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