Transient upregulation of postsynaptic IP3-gated Ca release underlies short-term potentiation of metabotropic glutamate receptor 1 signaling in cerebellar Purkinje cells.
Synaptic plasticity lasting approximately 100 s has been suggested to function as a temporary buffer for neural information. One example of this was reported by Batchelor and Garthwaite (1997), who found that a slow metabotropic glutamate receptor 1 (mGluR1)-evoked EPSP produced by burst stimulation of cerebellar parallel fiber-Purkinje cell synapses could be potentiated by a conditioning stimulus consisting of prior activation of climbing fiber synapses (or injection of depolarizing current) with a delay of up to 90 s. What is the molecular basis of the signal that spans this temporal gap? Here, we show that mGluR1-evoked slow EPSCs evoked by parallel fiber burst test stimuli show a similar form of short-term potentiation (mGluR1-STP) and that this phenomenon is also observed when parallel fiber bursts are replaced by pressure pulses of an exogenous mGluR1 agonist. Ca imaging experiments revealed that cytosolic Ca levels returned to baseline within several seconds after conditioning depolarization, indicating that this cannot underlie mGluR1-STP. To test the hypothesis that transient upregulation of inositol-1,4,5-trisphosphate (IP(3))-gated Ca release underlies this phenomenon, we used local photolytic uncaging of IP(3) to deplete IP(3)-gated Ca stores. IP(3) uncaging in the interval between conditioning depolarization and the test pulse produced a complete blockade of mGluR1-STP, as did blockade of IP(3) receptors with heparin. When Ca transients evoked by IP(3) uncaging were used as a test stimulus, conditioning depolarization produced a large STP of Ca response amplitudes. These data suggest that transient upregulation of postsynaptic IP(3)-gated Ca signaling constitutes a novel form of short-term synaptic plasticity.
Kim
Sang Jeong
SJ
Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Jin
Yunju
Y
Kim
Jun
J
Shin
Jung Hoon
JH
Worley
Paul F
PF
Linden
David J
DJ
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009924:Organ Culture Techniques; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
D053496:Inositol 1,4,5-Trisphosphate Receptors; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1