title: Calcium-dependent phosphorylation regulates neuronal stability and plasticity in a highly precise pacemaker nucleus.
abstract: Specific types of neurons show stable, predictable excitability properties, while other neurons show transient adaptive plasticity of their excitability. However, little attention has been paid to how the cellular pathways underlying adaptive plasticity interact with those that maintain neuronal stability. We addressed this question in the pacemaker neurons from a weakly electric fish because these neurons show a highly stable spontaneous firing rate as well as an N-methyl-D-aspartate (NMDA) receptor-dependent form of plasticity. We found that basal firing rates were regulated by a serial interaction of conventional and atypical PKC isoforms and that this interaction establishes individual differences within the species. We observed that NMDA receptor-dependent plasticity is achieved by further activation of these kinases. Importantly, the PKC pathway is maintained in an unsaturated baseline state to allow further Ca(2+)-dependent activation during plasticity. On the other hand, the Ca(2+)/calmodulin-dependent phosphatase calcineurin does not regulate baseline firing but is recruited to control the duration of the NMDA receptor-dependent plasticity and return the pacemaker firing rate back to baseline. This work illustrates how neuronal plasticity can be realized by biasing ongoing mechanisms of stability (e.g., PKC) and terminated by recruiting alternative mechanisms (e.g., calcineurin) that constrain excitability. We propose this as a general model for regulating activity-dependent change in neuronal excitability.
authors.affiliation: Section of Neurobiology and Institute for Neuroscience, Patterson Laboratory, University of Texas at Austin, Texas, USA. ageorge@biology2.wustl.edu
authors.forename: Andrew A
authors.initials: AA
authors.lastname: George
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Macleod
authors.forename: Harold H
authors.initials: HH
authors.lastname: Zakon
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D004555:Electric Fish / Q000378:metabolism / Q000502:physiology; D005260:Female; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology; D012737:Sex Factors
chemical_list: D007527:Isoenzymes; D016194:Receptors, N-Methyl-D-Aspartate; D011493:Protein Kinase C; D019703:Calcineurin; D002118:Calcium