Phospholipase A2 controls the induction of short-term versus long-term depression in the cerebellar Purkinje neuron in culture

Cerebellar long-term depression (LTD) may be reliably induced in the cultured Purkinje neuron when glutamate pulses and Purkinje neuron depolarization are applied together 6 times. When the number of these conjunctive stimuli was reduced to 2, a short-term depression (STD) lasting 20-40 min was induced in 4/12 cells. The enzyme phospholipase A2 cleaves membrane phospholipids causing liberation of free unsaturated fatty acids, which in turn synergistically activate protein kinase C when present with diacylglycerol and Ca. Application of free unsaturated fatty acids with 2 conjunctive stimuli resulted in an apparent conversion of STD cases to LTD. Application of phospholipase A2 inhibitors during 6 conjunctions converted LTD to STD. These findings suggest a model in which liberation of unsaturated fatty acids by phospholipase A2 contributes to a synergistic activation of protein kinase C, the full activation of which results in LTD induction, and the partial activation of which results in STD induction.