INDUCTION OF LONG-TERM DEPRESSION AND REBOUND POTENTIATION BY INOSITOL TRISPHOSPHATE IN CEREBELLAR PURKINJE NEURONS

Cerebellar Purkinje neurons receive two major excitatory inputs, the c limbing fibers (CFs) and parallel fibers (PFs). Simultaneous, repeated activation of CFs and PFs results in the long-term depression (LTD) o f the amplitude of PF-evoked synaptic currents. To induce LTD, activat ion of CFs may be substituted with depolarization of the Purkinje neur on to turn on voltage-activated calcium channels and increase the intr acellular calcium concentration. The role of PFs in the induction of L TD, however, is less clear. PFs activate glutamate metabotropic recept ors that increase phosphoinositide turnover and elevate cytosolic inos itol 1,4,5-trisphosphate (InsP(3)). It has been proposed that calcium release from intracellular stores via InsP(3) receptors may be importa nt in the induction of LTD. We studied the role of InsP(3) in the indu ction of LTD by photolytic release of InsP(3) from its biologically in active ''caged'' precursor in voltage-clamped Purkinje neurons in acut ely prepared cerebellar slices. We find that InsP(3)-evoked calcium re lease is as effective in LTD induction as activation of PFs. InsP(3)-i nduced LTD was prevented by calcium chelator 1,2-bis(2-amino phenoxy) ethane-N,N,N',N'-tetraacetic acid. LTD produced either by repeated act ivation of PFs combined with depolarization (PF+Delta V), or by InsP(3 ) combined with depolarization (InsP(3)+Delta V) saturated at approxim ate to 50%. Maximal LTD induced by PF+Delta V could not be further inc reased by InsP(3)+Delta V and vice versa, which suggests that both pro tocols for induction of LTD share a common path. In addition to induci ng LTD, photorelease of InsP(3)+Delta V resulted in the rebound potent iation 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 ro le in LTD induction under physiological conditions.