title: Activity-dependent feedback regulates correlated ion channel mRNA levels in single identified motor neurons.
abstract: Neurons generate cell-specific outputs via interactions of conductances carried by ion channel proteins that are homeostatically regulated to maintain key quantitative relationships among subsets of conductances. Given the challenges of both normal channel protein turnover and short-term plasticity, how is the balance of membrane conductances maintained over long-term timescales to ensure stable electrophysiological phenotype? One possible mechanism is to dynamically regulate production of channel protein via feedback that constrains relationships at the channel mRNA level. Recent modeling work has postulated that such mRNA relationships could emerge as a result of activity-dependent homeostatic tuning rules that ensure an appropriate ratio of mRNA for key ion channels is maintained to preserve robust cellular output. Yet, this has never been demonstrated in biological neurons. In this study, we quantified multiple ion channel mRNAs from single identified motor neurons of the stomatogastric ganglion to determine whether correlations among channel mRNAs are actively maintained, and, if so, by what form of feedback. In these neurons, we identified correlations among mRNAs for voltage-gated calcium and potassium channels. By performing experiments that decoupled activity, synaptic connectivity, and neuromodulatory state, we determined that correlated channel mRNAs are maintained by an activity-dependent process. This is the first study to demonstrate that distinct relationships across channel mRNAs are dynamically maintained in an activity-dependent manner. This feedback from cellular activity to coordinated transcriptome-level interactions represents a novel aspect of regulation of neuronal output with implications for long-term stability of neuron function.
authors.affiliation: Division of Biological Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Temporal
authors.affiliation: Division of Biological Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: Kawasi M
authors.initials: KM
authors.lastname: Lett
authors.affiliation: Division of Biological Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA. Electronic address: schulzd@missouri.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Schulz
mesh_terms: D000818:Animals; D003386:Brachyura / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism*; D025461:Feedback, Physiological; D005260:Female; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D012333:RNA, Messenger