Subcellular interactions between parallel fibre and climbing fibre signals in Purkinje cells predict sensitivity of classical conditioning to interstimulus interval.
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.
Kotaleski
Jeanette Hellgren
JH
George Mason University, School of Computational Sciences, The Krasnow Institute for Advanced Studies, USA. jeanette@nada.kth.se
Lester
David
D
Blackwell
Kim T
KT
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
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