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The Journal of Neuroscience, April 7, 2004, 24(14):3618-3626; doi:10.1523/JNEUROSCI.3567-03.2004

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Cellular/Molecular
Optical Quantal Analysis Indicates That Long-Term Potentiation at Single Hippocampal Mossy Fiber Synapses Is Expressed through Increased Release Probability, Recruitment of New Release Sites, and Activation of Silent Synapses

Christopher A. Reid,^1 * Don B. Dixon,^1 * Michiko Takahashi,¹ Tim V. P. Bliss,¹ and Alan Fine^1,2

¹Division of Neurophysiology, National Institute for Medical Research, London NW7 1AA, United Kingdom, and ²Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada

It is generally believed that long-term potentiation (LTP) at hippocampal mossy fiber synapses between dentate granule and CA3 pyramidal cells is expressed through presynaptic mechanisms leading to an increase in quantal content. The source of this increase has remained undefined but could include enhanced probability of transmitter release at existing functional release sites or increases in the number of active release sites. We performed optical quantal analyses of transmission at individual mossy fiber synapses in cultured hippocampal slices, using confocal microscopy and intracellular fluorescent Ca²⁺ indicators. Our results indicate that LTP is expressed at functional synapses by both increased probability of transmitter release and recruitment of new release sites, including the activation of previously silent synapses here visualized for the first time.

Key words: quantal analysis; synapse; plasticity; long-term potentiation; silent synapse; hippocampus; calcium; confocal microscopy; dendritic spine; mossy fiber; CA3 pyramidal cell; fluorescence imaging

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Received July 30, 2003; revised February 16, 2004; accepted February 20, 2004.

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