代謝型GABA受容体‐代謝型グルタミン酸受容体クロストークによる小脳プルキンエ細胞LTDの増強

抄録

Type-1 metabotropic glutamate receptor (mGluR1) in cerebellar Purkinje cells (PCs) plays a central role in induction of cerebellar long-term depression (LTD), a form of synaptic plasticity crucial for cerebellar motor learning. We previously revealed complex formation between mGluR1 and B-type γ-aminobutyric acid receptor (GABA_BR) in PCs. Here we examined in cultured mouse PCs whether and how GABA_BR influences LTD of the postsynaptic glutamate-responsiveness (LTD_glu) that is induced by conjunctive dendritic glutamate application and somatic depolarization. GABA and baclofen, GABA_BR agonists increased the magnitude of LTD_glu. This effect was mimicked by mastoparan, a G_i/o protein activator and abolished by pertussis toxin, a G_i/o protein inhibitor. Baclofen augmented Ca²⁺ release from the intracellular stores, a response coupled to mGluR1 via phospholipase C. These findings suggest that GABA_BR enhances LTD_glu by potentiating the downstream signaling of mGluR1 via G_i/o protein. Moreover, in mouse cerebellar slices, CGP55845, a GABA_BR inhibitor decreased the magnitude of LTD at parallel fiber-PC synapses. GABA_BR-mGluR1 crosstalk may regulate the extent of cerebellar LTD in situ. [J Physiol Sci. 2008;58 Suppl:S120]