title: Extracellular calcium regulates postsynaptic efficacy through group 1 metabotropic glutamate receptors.
abstract: 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.
authors.affiliation: The University Laboratory of Physiology, Oxford University, Oxford OX1 3PT, United Kingdom. sbinrh@cardiff.ac.uk
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hardingham
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Bannister
authors.forename: Jenny C A
authors.initials: JC
authors.lastname: Read
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Fox
authors.forename: Giles E
authors.initials: GE
authors.lastname: Hardingham
authors.forename: J Julian B
authors.initials: JJ
authors.lastname: Jack
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D005110:Extracellular Space / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
chemical_list: D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D008274:Magnesium; D002118:Calcium