title: Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons.
abstract: Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons to environmental stimuli, coded in the pattern of action potential firing, can be very sensitive to the temporal nature of action potential delivery rather than the intensity of stimulation or the total number of action potentials delivered. These data identify temporal kinetics of action potential firing as critical components regulating intracellular signalling pathways and gene expression in neurons to extracellular cues during early development and throughout life.
authors.affiliation: Nervous System Development and Plasticity Section, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Lee
authors.affiliation: Nervous System Development and Plasticity Section, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Cohen
authors.affiliation: Department of Pathology, New York Medical College, Valhalla, NY, USA.|DP Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: Dumitru A
authors.initials: DA
authors.lastname: Iacobas
authors.affiliation: Department of Pathology, New York Medical College, Valhalla, NY, USA.
authors.forename: Sanda
authors.initials: S
authors.lastname: Iacobas
authors.affiliation: Nervous System Development and Plasticity Section, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, USA.
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Fields
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000465:Algorithms; D000818:Animals; D002478:Cells, Cultured; D016000:Cluster Analysis; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction