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The Journal of Neuroscience, January 2, 2008, 28(1):133-142; doi:10.1523/JNEUROSCI.1729-07.2008

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Cellular/Molecular
Order-Dependent Coincidence Detection in Cerebellar Purkinje Neurons at the Inositol Trisphosphate Receptor

Dmitry V. Sarkisov and Samuel S.-H. Wang

Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544

Correspondence should be addressed to Samuel Wang, Department of Molecular Biology and Princeton Institute for Neuroscience, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544. Email: sswang{at}princeton.edu

Associative long-term depression (LTD) at cerebellar parallel fiber–Purkinje cell synapses is sensitive to the temporal order in which the parallel fiber is coactivated with the climbing fiber input, but how order sensitivity is achieved is unknown. Here we show that the cerebellar inositol-1,4,5-trisphosphate (IP₃) receptor, whose activation is required for LTD induction, is sensitive in situ to the order of presentation of its coagonists, IP₃ and cytoplasmic calcium. By focally photolyzing a novel caged IP₃ compound in dendritic spines, we find that pairing IP₃ with climbing fiber-mediated calcium entry leads to a large calcium release transient if the climbing fiber is activated up to 100 ms before or up to 500 ms after IP₃ uncaging. This asymmetric timing window for coactivation follows the kinetics of calcium removal and IP₃ unbinding from the receptor and is not limited by IP₃ metabolism. IP₃ receptor binding thus acts as an eligibility trace that can drive temporal order-dependent calcium release and LTD induction in Purkinje cells and event order-dependent sensory plasticity in the whole animal.

Key words: coincidence detection; inositol trisphosphate receptor; IP₃; calcium channels; LTD (long-term depression); plasticity; Purkinje neurons

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Received April 17, 2007; revised Oct. 28, 2007; accepted Nov. 1, 2007.

Correspondence should be addressed to Samuel Wang, Department of Molecular Biology and Princeton Institute for Neuroscience, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544. Email: sswang{at}princeton.edu

Related articles in J. Neurosci.:

The Calcium Kinetics and Inositol Trisphosphate Receptor Properties Shape the Asymmetric Timing Window of Coincidence Detection

Hideaki Ogasawara
J. Neurosci. 2008 28: 4293-4294. [Full Text]  

This article has been cited by other articles:

				S.-A. Brown, F. Morgan, J. Watras, and L. M. Loew Analysis of Phosphatidylinositol-4,5-Bisphosphate Signaling in Cerebellar Purkinje Spines Biophys. J., August 15, 2008; 95(4): 1795 - 1812. [Abstract] [Full Text] [PDF]

				H. Ogasawara The Calcium Kinetics and Inositol Trisphosphate Receptor Properties Shape the Asymmetric Timing Window of Coincidence Detection J. Neurosci., April 23, 2008; 28(17): 4293 - 4294. [Full Text] [PDF]

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