title: Subcellular interactions between parallel fibre and climbing fibre signals in Purkinje cells predict sensitivity of classical conditioning to interstimulus interval.
abstract: Classical conditioning of the nictitating membrane response requires a specific temporal interval between conditioned stimulus and unconditioned stimulus, and produces an increase in Protein Kinase C (PKC) activation in Purkinje cells. To evaluate whether biochemical interactions within the Purkinje cell may explain the temporal sensitivity, a model of PKC activation by Ca2+, diacylglycerol (DAG), and arachidonic acid (AA) is developed. Ca2+ elevation is due to CF stimulation and IP3 induced Ca2+ release (IICR). DAG and IP3 result from PF stimulation, while AA results from phospholipase A2 (PLA2). Simulations predict increased PKC activation when PF stimulation precedes CF stimulation by 0.1 to 3 s. The sensitivity of IICR to the temporal relation between PF and CF stimulation, together with the buffering system of Purkinje cells, significantly contribute to the temporal sensitivity.
authors.affiliation: George Mason University, School of Computational Sciences, The Krasnow Institute for Advanced Studies, USA. jeanette@nada.kth.se
authors.forename: Jeanette Hellgren
authors.initials: JH
authors.lastname: Kotaleski
authors.forename: David
authors.initials: D
authors.lastname: Lester
authors.forename: Kim T
authors.initials: KT
authors.lastname: Blackwell
mesh_terms: D000465:Algorithms; D016718:Arachidonic Acid / Q000378:metabolism; D001767:Blinking / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D003198:Computer Simulation; D003214:Conditioning, Classical / Q000502:physiology*; D004075:Diglycerides / Q000096:biosynthesis; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D007293:Inosine Triphosphate / Q000096:biosynthesis; D007700:Kinetics; D008563:Membrane Lipids / Q000378:metabolism; D008959:Models, Neurological; D008960:Models, Psychological; D009412:Nerve Fibers / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010812:Physical Stimulation; D011493:Protein Kinase C / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D017470:Receptors, Glutamate / Q000187:drug effects; D013347:Subcellular Fractions / Q000378:metabolism / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D004075:Diglycerides; D008563:Membrane Lipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D017470:Receptors, Glutamate; D007293:Inosine Triphosphate; D016718:Arachidonic Acid; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium