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 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.
Lev-Ram
V
V
Department of Pharmacology, University of California, San Diego, La Jolla 92093-0647, USA.
Makings
L R
LR
Keitz
P F
PF
Kao
J P
JP
Tsien
R Y
RY
D000200:Action Potentials; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002248:Carbon Monoxide / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology* / Q000528:radiation effects; D019335:Nitroarginine; D010108:Oxyhemoglobins / Q000494:pharmacology; D010782:Photolysis; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D010108:Oxyhemoglobins; D019335:Nitroarginine; D009569:Nitric Oxide; D002248:Carbon Monoxide; D001120:Arginine; D002118:Calcium