Reversing cerebellar long-term depression.
The discovery of a postsynaptically expressed form of cerebellar parallel fiber-Purkinje cell long-term potentiation (LTP) raises the question whether this is the long-sought resetting mechanism for long-term depression (LTD). Extracellular monitoring of PC spikes enables stable prolonged recordings of parallel fiber-Purkinje cell synaptic efficacy. LTD, saturated by repeated induction protocols, can be reversed by a single round of postsynaptic LTP or nitric oxide (NO), enabling LTD to be reinduced. Conversely, after postsynaptic LTP has been saturated, one round of LTD permits fresh postsynaptic LTP. By contrast, after saturation of LTD, induction of presynaptic LTP or application of forskolin leaves LTD still saturated. Likewise, presynaptic LTP cannot be reversed by LTD. Therefore postsynaptic LTP mediated by NO without postsynaptic Ca2+ elevation, unlike presynaptic LTP mediated by cAMP, is a true counterbalance to LTD mediated by coincidence of NO plus postsynaptic Ca2+
Lev-Ram
Varda
V
Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093-0647, USA.
Mehta
Samar B
SB
Kleinfeld
David
D
Tsien
Roger Y
RY
D000818:Animals; D002531:Cerebellum / Q000502:physiology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D017774:Long-Term Potentiation / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats
D009569:Nitric Oxide