Participation of postsynaptic PKC in cerebellar long-term depression in culture.
Long-term depression (LTD) in the intact cerebellum is a decrease in the efficacy of the parallel fiber-Purkinje neuron synapse induced by coactivation of climbing fiber and parallel fiber inputs. In cultured Purkinje neurons, a similar depression can be induced by iontophoretic glutamate pulses and Purkinje neuron depolarization. This form of LTD is expressed as a depression of alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid (AMPA)-mediated current, and its induction is dependent on activation of metabotropic quisqualate receptors. The effect of inhibitors of protein kinase C (PKC) on LTD induction was studied. Inhibitors of PKC blocked LTD induction, while phorbol-12,13-diacetate (PDA), a PKC activator, mimicked LTD. These results suggest that PKC activation is necessary for the induction of cerebellar LTD.
Linden
D J
DJ
Department of Neurosciences, Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110.
Connor
J A
JA
D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles; D051379:Mice; D009281:Naphthalenes; D010703:Phorbol Esters / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D016318:Quisqualic Acid / Q000494:pharmacology; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter / Q000502:physiology; D013570:Synaptic Membranes / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D007211:Indoles; D009281:Naphthalenes; D010703:Phorbol Esters; D011083:Polycyclic Compounds; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D011493:Protein Kinase C; C058819:calphostin C; D002118:Calcium; C064758:Ro 31-8220