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The Journal of Neuroscience, June 7, 2006, 26(23):6337-6345; doi:10.1523/JNEUROSCI.5128-05.2006

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Cellular/Molecular
Extracellular Calcium Regulates Postsynaptic Efficacy through Group 1 Metabotropic Glutamate Receptors

Neil R. Hardingham,¹ Neil J. Bannister,¹ Jenny C. A. Read,¹ Kevin D. Fox,² Giles E. Hardingham,³ and J. Julian B. Jack¹

¹The University Laboratory of Physiology, Oxford University, Oxford OX1 3PT, United Kingdom, ²The School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom, and ³Centre for Neuroscience Research, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH9 1QH, United Kingdom

Correspondence should be addressed to Dr. Neil R. Hardingham, Biosi 3, The School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, UK. Email: sbinrh{at}cardiff.ac.uk

Bursts of synaptic transmission are known to induce transient depletion of Ca²⁺ within the synaptic cleft. Although Ca²⁺ depletion has been shown to lower presynaptic release probability, effects on the postsynaptic cell have not been reported. In this study, we show that physiologically relevant reductions in extracellular Ca²⁺ lead to a decrease in synaptic strength between synaptically coupled layer 2/3 cortical pyramidal neurons. Using quantal analysis and mEPSP analysis, we demonstrate that a lowered extracellular Ca²⁺ produces a reduction in the postsynaptic quantal size in addition to its known effect on release probability. An elevated Mg²⁺ level can prevent this reduction in postsynaptic efficacy at subphysiological Ca²⁺ levels. We show that the calcium-dependent effect on postsynaptic quantal size is mediated by group 1 metabotropic glutamate receptors, acting via CaMKII (Ca²⁺/calmodulin-dependent protein kinase II) and PKC. Therefore, physiologically relevant changes in extracellular Ca²⁺ can regulate information transfer at cortical synapses via both presynaptic and postsynaptic mechanisms.

Key words: calcium [Ca]; metabotropic glutamate receptor; cortex; postsynaptic; CaMK-II; protein kinase C

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Received Dec. 2, 2005; revised May 4, 2006; accepted May 4, 2006.

Correspondence should be addressed to Dr. Neil R. Hardingham, Biosi 3, The School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, UK. Email: sbinrh{at}cardiff.ac.uk

This article has been cited by other articles:

				N. R. Hardingham, G. E. Hardingham, K. D. Fox, and J. J. B. Jack Presynaptic Efficacy Directs Normalization of Synaptic Strength in Layer 2/3 Rat Neocortex After Paired Activity J Neurophysiol, April 1, 2007; 97(4): 2965 - 2975. [Abstract] [Full Text] [PDF]

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