title: Persistent changes in spontaneous firing of Purkinje neurons triggered by the nitric oxide signaling cascade.
abstract: Many types of neurons fire spontaneously because of the activity of pacemaking ion channels. Although endogenous firing can serve as a persistent signal to downstream targets, little attention has been paid to factors that might modulate such intrinsic electrical activity. We tested for modulation of spontaneous firing of Purkinje neurons in cerebellar slices under conditions in which principal synaptic inputs were blocked. Loose-patch recordings from single neurons show that sustained (>40 min) increases in the spontaneous firing rate can be triggered by activation of the nitric oxide-cGMP signaling pathway. Inhibitors of soluble guanylate cyclase and protein kinase G block this modulation. Increases in firing rate are also observed after stimulation of parallel fibers but not in response to basket cell activity. These findings elucidate a novel role for the nitric oxide-cGMP signaling cascade in the brain. This mechanism could permit long-term adjustments in the baseline firing rate of endogenously active neurons in response to changes in afferent activity.
authors.affiliation: Department of Neurobiology and Brain Research Institute, University of California at Los Angeles School of Medicine, Los Angeles, California 90095, USA.
authors.forename: Spencer L
authors.initials: SL
authors.lastname: Smith
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Otis
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002531:Cerebellum / Q000166:cytology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006162:Guanylate Cyclase; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000071756:Soluble Guanylyl Cyclase; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D020030:Nitric Oxide Donors; D018160:Receptors, Cytoplasmic and Nuclear; D013873:Thionucleotides; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D019001:Nitric Oxide Synthase; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP