| Title | Linking genetically defined neurons to behavior through a broadly applicable silencing allele. | | Author(s) | Kim JC, Cook MN, Carey MR, Shen C, Regehr WG, Dymecki SM | | Institution | Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. | | Source | Neuron 2009 Aug 13; 63(3):305-15. | | MeSH | Acoustic Stimulation
Analysis of Variance
Animals
Animals, Newborn
Basic Helix-Loop-Helix Transcription Factors
Behavior, Animal
Biophysics
Cerebellum
Conditioning (Psychology)
Electric Stimulation
Exploratory Behavior
Fear
GABA Antagonists
Green Fluorescent Proteins
Linkage (Genetics)
Maze Learning
Mice
Mice, Transgenic
Microscopy, Electron, Transmission
Models, Neurological
Nerve Tissue Proteins
Neurons
Patch-Clamp Techniques
Phenotype
Phosphinic Acids
Propanolamines
Proteins
Recombinases
Serotonin
Startle Reaction
Synaptic Transmission
Tetanus Toxin
Vesicle-Associated Membrane Protein 2
| | Abstract | Tools for suppressing synaptic transmission gain power when able to target highly selective neuron subtypes, thereby sharpening attainable links between neuron type, behavior, and disease; and when able to silence most any neuron subtype, thereby offering broad applicability. Here, we present such a tool, RC::PFtox, that harnesses breadth in scope along with high cell-type selection via combinatorial gene expression to deliver tetanus toxin light chain (tox), an inhibitor of vesicular neurotransmission. When applied in mice, we observed cell-type-specific disruption of vesicle exocytosis accompanied by loss of excitatory postsynaptic currents and commensurately perturbed behaviors. Among various test populations, we applied RC::PFtox to silence serotonergic neurons, en masse or a subset defined combinatorially. Of the behavioral phenotypes observed upon en masse serotonergic silencing, only one mapped to the combinatorially defined subset. These findings provide evidence for separability by genetic lineage of serotonin-modulated behaviors; collectively, these findings demonstrate broad utility of RC::PFtox for dissecting neuron functions. | | Language | eng | | Pub Type(s) | In Vitro
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19679071 |
|
