Induction of long-term depression and rebound potentiation by inositol trisphosphate in cerebellar Purkinje neurons

Cerebellar Purkinje neurons receive two major excitatory inputs, the climbing fibers (CFs) and parallel fibers (PFs). Simultaneous, repeated activation of CFs and PFs results in the long-term depression (LTD) of the amplitude of PF-evoked synaptic currents. To induce LTD, activation of CFs may be substituted with depolarization of the Purkinje neuron to turn on voltage-activated calcium channels and increase the intracellular calcium concentration. The role of PFs in the induction of LTD, however, is less clear. PFs activate glutamate metabotropic receptors that increase phosphoinositide turnover and elevate cytosolic inositol 1,4,5-trisphosphate (InsP(3)). It has been proposed that calcium release from intracellular stores via InsP(3) receptors may be important in the induction of LTD. We studied the role of InsP(3) in the induction of LTD by photolytic release of InsP(3) from its biologically inactive ''caged'' precursor in voltage-clamped Purkinje neurons in acutely prepared cerebellar slices. We find that InsP(3)-evoked calcium release is as effective in LTD induction as activation of PFs. InsP(3)-induced LTD was prevented by calcium chelator 1,2-bis(2-amino phenoxy) ethane-N,N,N',N'-tetraacetic acid. LTD produced either by repeated activation of PFs combined with depolarization (PF+Delta V), or by InsP(3) combined with depolarization (InsP(3)+Delta V) saturated at approximate to 50%. Maximal LTD induced by PF+Delta V could not be further increased by InsP(3)+Delta V and vice versa, which suggests that both protocols for induction of LTD share a common path. In addition to inducing LTD, photorelease of InsP(3)+Delta V resulted in the rebound potentiation of inhibitory synaptic currents. In the presence of heparin, an InsP(3) receptor antagonist, repeated activation of PF+Delta V failed to induce LTD, suggesting that InsP(3) receptors play an important role in LTD induction under physiological conditions.