title: Opposing functions of CREB and MKK1 synergistically regulate the geometry of dendritic spines in visual cortex.
abstract: Most excitatory inputs onto pyramidal neurons are made on dendritic spines. The geometry of dendritic spines modulates synaptic function; yet we know little regarding the molecular signals that regulate spine geometry. Here we report that neurons coordinately regulate the geometry of spines to compensate for variability in spine number, by a process requiring the transcription factor CREB and the kinase MKK1. We find that CREB function is induced, whereas MKK1 is inhibited, by activity blockade. To obtain evidence that CREB and MKK1 regulate dendritic spine geometry in vivo, we coexpressed green fluorescent protein and dominant negative CREB or MKK1 in pyramidal neurons of the intact rat visual cortex. Spines on apical dendrites of layer 3 neurons were then characterized by confocal microscopy. We find that CREB and MKK1 regulate spine geometry in opposite ways. MKK1 is required to reduce spine head size when spine density is high, whereas CREB is required to enlarge spines when spine density is low. Our data suggest that CREB and MKK1 might function as complementary negative feedback mechanisms to maintain synaptic drive within bounds.
authors.affiliation: Department of Molecular and Cellular Biology, Psychiatry and Behavioral Sciences, and Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Seigo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhou
authors.forename: John F
authors.initials: JF
authors.lastname: Neumaier
authors.forename: Tony A
authors.initials: TA
authors.lastname: Pham
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001931:Brain Mapping; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D049229:Dendritic Spines / Q000502:physiology* / Q000648:ultrastructure; D004569:Electroencephalography; D005074:Evoked Potentials, Visual / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000502:physiology*; D018613:Microscopy, Confocal; D008954:Models, Biological; D010775:Photic Stimulation / Q000379:methods; D017966:Pyramidal Cells / Q000187:drug effects / Q000648:ultrastructure*; D051381:Rats; D020318:Rats, Long-Evans; D012044:Regression Analysis; D013779:Tetrodotoxin / Q000494:pharmacology; D014793:Visual Cortex / Q000166:cytology*
chemical_list: D000779:Anesthetics, Local; D017362:Cyclic AMP Response Element-Binding Protein; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D048369:MAP Kinase Kinase 1