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 (PLA(2)). 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.