LONG-TERM DEPRESSION IN CEREBELLAR PURKINJE NEURONS RESULTS FROM COINCIDENCE OF NITRIC-OXIDE AND DEPOLARIZATION-INDUCED CA2+ TRANSIENTS

The role of nitric oxide (NO) in the induction of longterm depression (LTD) in the cerebellum was explored using a new, organic, membrane-im permeant form of caged NO. NO photolytically released inside Purkinje neurons mimicked parallel fiber (PF) activity in synergizing with brie f postsynaptic depolarization to induce LTD. Such LTD required a delay of <50 ms between the end of photolysis and the onset of depolarizati on, was prevented by intracellular Ca2+ chelation, and was mutually oc clusive with LTD conventionally produced by PF activation plus depolar ization. Bath application of NO synthase inhibitor or of myoglobin, a NO trap, prevented LTD induction via PF stimulation, but not that from intracellular uncaged NO, whereas intracellular myoglobin blocked bot h protocols. NO is therefore an anterograde transmitter in LTD inducti on. A biochemical requirement for simultaneous NO and elevation of int racellular free Ca2+ would explain why PF activity must coincide with postsynaptic action potentials.