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The Journal of Neuroscience, July 30, 2008, 28(31):7765-7773; doi:10.1523/JNEUROSCI.1296-08.2008

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Cellular/Molecular
Analog Modulation of Mossy Fiber Transmission Is Uncoupled from Changes in Presynaptic Ca²⁺

Ricardo Scott, Arnaud Ruiz, Christian Henneberger, Dimitri M. Kullmann, and Dmitri A. Rusakov

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

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

Subthreshold somatic depolarization has been shown recently to modulate presynaptic neurotransmitter release in cortical neurons. To understand the mechanisms underlying this mode of signaling in the axons of dentate granule cells (hippocampal mossy fibers), we have combined two-photon Ca²⁺ imaging with dual-patch recordings from somata and giant boutons forming synapses on CA3 pyramidal cells. In intact axons, subthreshold depolarization propagates both orthodromically and antidromically, with an estimated length constant of 200–600 µm depending on the signal waveform. Surprisingly, presynaptic depolarization sufficient to enhance glutamate release at mossy fiber–CA3 pyramidal cell synapses has no detectable effect on either basal Ca²⁺-dependent fluorescence or action-potential-evoked fluorescence transients in giant boutons. We further estimate that neurotransmitter release varies with presynaptic Ca²⁺ entry with a 2.5-power relationship and that depolarization-induced synaptic facilitation remains intact in the presence of high-affinity presynaptic Ca²⁺ buffers or after blockade of local Ca²⁺ stores. We conclude that depolarization-dependent modulation of transmission at these boutons does not rely on changes in presynaptic Ca²⁺.

Key words: synaptic transmission; mossy fiber; analog modulation; hippocampus; dual-patch recordings; biophysical modeling

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Received Nov. 21, 2007; revised May 14, 2008; accepted June 11, 2008.

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

This article has been cited by other articles:

				T. Hori and T. Takahashi Mechanisms underlying short-term modulation of transmitter release by presynaptic depolarization J. Physiol., June 15, 2009; 587(12): 2987 - 3000. [Abstract] [Full Text] [PDF]

				R. Scott, T. Lalic, D. M. Kullmann, M. Capogna, and D. A. Rusakov Target-Cell Specificity of Kainate Autoreceptor and Ca2+-Store-Dependent Short-Term Plasticity at Hippocampal Mossy Fiber Synapses J. Neurosci., December 3, 2008; 28(49): 13139 - 13149. [Abstract] [Full Text] [PDF]

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