Linking Genetically Defined Neurons to Behavior through a Broadly Applicable Silencing Allele

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...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2009-08, Vol.63 (3), p.305-315
Main Authors: Kim, Jun Chul, Cook, Melloni N., Carey, Megan R., Shen, Chung, Regehr, Wade G., Dymecki, Susan M.
Format: Article
Language:English
Subjects:
Acoustic Stimulation - methods
Analysis of Variance
Animals
Animals, Newborn
Basic Helix-Loop-Helix Transcription Factors - metabolism
Behavior
Behavior, Animal - physiology
Biophysics
Cerebellum - anatomy & histology
Cerebellum - cytology
Cerebellum - metabolism
Conditioning (Psychology) - physiology
Electric Stimulation - methods
Exploratory Behavior - physiology
Fear - physiology
GABA Antagonists - pharmacology
Genetic Linkage - physiology
Green Fluorescent Proteins - genetics
In Vitro Techniques
Maze Learning - physiology
Mice
Mice, Transgenic
Microscopy, Electron, Transmission - methods
Models, Neurological
MOLNEURO
Nerve Tissue Proteins - metabolism
Neurons
Neurons - physiology
Neurons - ultrastructure
Patch-Clamp Techniques
Phenotype
Phosphinic Acids - pharmacology
Propanolamines - pharmacology
Proteins
Proteins - genetics
Recombinases - genetics
Reflex, Startle - genetics
RNA, Untranslated
Rodents
Serotonin - metabolism
Synaptic Transmission - genetics
Synaptic Transmission - physiology
Tetanus Toxin - chemistry
Tetanus Toxin - metabolism
Vesicle-Associated Membrane Protein 2 - metabolism
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Description
Summary: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.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2009.07.010