title: Decreased dendritic spine density as a consequence of tetanus toxin light chain expression in single neurons in vivo.
abstract: Tetanus toxin light chain has been used for some time as a genetically-encoded tool to inhibit neurotransmission and thereby dissect mechanisms underlying neural circuit formation and function. In addition to cleaving v-SNARE proteins involved in axonal neurotransmitter release, tetanus toxin light chain can also block activity-dependent dendritic exocytosis. The application of tetanus toxin light chain as a research tool in mammalian models, however, has been limited to a small number of cell types. Here we have induced expression of tetanus toxin light chain in a very small number of fluorescently labeled neurons in many regions of the adult mouse brain. This was achieved by crossing SLICK (single-neuron labeling with inducible cre-mediated knockout) transgenic lines with RC::Ptox mice that have Cre recombinase-controlled expression of the tetanus toxin light chain. Using this system we have examined the cell-autonomous effects of tetanus toxin light chain expression on dendritic spines in vivo. We find that dendritic spine density is reduced by 15% in tetanus toxin expressing hippocampal CA1 pyramidal cells, while spine morphology is unaltered. This effect is likely to be a consequence of inhibition of activity-dependent dendritic exocytosis and suggests that on-going plasticity-associated exocytosis is required for long-term dendritic spine maintenance in vivo.
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland; Department of Cognitive, Linguistic and Psychological Sciences, Brown University, Providence, RI 02912, USA. Electronic address: victoria_heimer-mcginn@brown.edu.
authors.forename: Victoria
authors.initials: V
authors.lastname: Heimer-McGinn
authors.forename: Anita C H
authors.initials: AC
authors.lastname: Murphy
authors.forename: Jun Chul
authors.initials: JC
authors.lastname: Kim
authors.forename: Susan M
authors.initials: SM
authors.lastname: Dymecki
authors.forename: Paul W
authors.initials: PW
authors.lastname: Young
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013744:Tetanus Toxin / Q000235:genetics / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin; D049452:Green Fluorescent Proteins; D008666:Metalloendopeptidases; C093556:zinc-endopeptidase, tetanus neurotoxin
keywords: Dendritic exocytosis; Dendritic spines; Interneuronal competition; SLICK; Tetanus toxin light chain
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