Long-term depression in cerebellar Purkinje neurons results from coincidence of nitric oxide and depolarization-induced Ca2+ transients

Neuron. 1995 Aug;15(2):407-15. doi: 10.1016/0896-6273(95)90044-6.


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

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Calcium / physiology*
  • Carbon Monoxide / pharmacology
  • Neuronal Plasticity / physiology*
  • Nitric Oxide / physiology*
  • Nitric Oxide / radiation effects
  • Nitroarginine
  • Oxyhemoglobins / pharmacology
  • Photolysis
  • Purkinje Cells / physiology*
  • Rats
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Oxyhemoglobins
  • Nitroarginine
  • Nitric Oxide
  • Carbon Monoxide
  • Arginine
  • Calcium