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.

Nyckelord

classical conditioning

Purkinje cell

protein kinase C

IP3 induced calcium release

computer modeling

LTD

long-term depression

inositol 1,4,5-trisphosphate

calcium

membrane

range

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ref (ämneskategori)

art (ämneskategori)