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The Journal of Neuroscience, October 27, 2004, 24(43):9612-9622; doi:10.1523/JNEUROSCI.5583-03.2004

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Cellular/Molecular
Calcium Release from Presynaptic Ryanodine-Sensitive Stores Is Required for Long-Term Depression at Hippocampal CA3-CA3 Pyramidal Neuron Synapses

Vivek K. Unni,1 Stanislav S. Zakharenko,1 Leonard Zablow,1,3 Anthony J. DeCostanzo,2 and Steven A. Siegelbaum1,2,3

1Center for Neurobiology and Behavior, 2Department of Pharmacology, and 3Howard Hughes Medical Institute, Columbia University, New York, New York 10032

Although Ca2+ release from internal stores has been proposed to be important for the induction of long-term synaptic plasticity, the importance of Ca2+ stores localized in presynaptic terminals remains unclear. Here, we have selectively applied pharmacological antagonists to either the presynaptic or postsynaptic cell in paired whole-cell recordings from hippocampal CA3 pyramidal neurons in slice culture. We demonstrate directly the necessary role of presynaptic, but not postsynaptic, ryanodine-sensitive Ca2+ stores in the induction of NMDA receptor (NMDAR)-dependent long-term depression (LTD). Using two-photon laser scanning microscopy, we further find that release from the ryanodine-sensitive stores during prolonged synaptic stimulation generates a slowly rising Ca2+ signal in the presynaptic terminal that is required for the induction of LTD. Moreover, this form of LTD has a significant presynaptic component of expression because it causes a marked decrease in the rate of release from CA3 neuron presynaptic terminals of FM 1-43, a fluorescent probe of synaptic vesicle cycling. Thus, Ca2+ release from presynaptic ryanodine-sensitive stores is critical in the induction of a presynaptic component of NMDAR-dependent LTD.

Key words: long-term depression; CA3; internal calcium stores; ryanodine-sensitive stores; hippocampus; synaptic plasticity


Received Dec 18, 2003; revised September 7, 2004; accepted September 9, 2004.




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