title: Functional labeling of neurons and their projections using the synthetic activity-dependent promoter E-SARE.
abstract: Identifying the neuronal ensembles that respond to specific stimuli and mapping their projection patterns in living animals are fundamental challenges in neuroscience. To this end, we engineered a synthetic promoter, the enhanced synaptic activity-responsive element (E-SARE), that drives neuronal activity-dependent gene expression more potently than other existing immediate-early gene promoters. Expression of a drug-inducible Cre recombinase downstream of E-SARE enabled imaging of neuronal populations that respond to monocular visual stimulation and tracking of their long-distance thalamocortical projections in living mice. Targeted cell-attached recordings and calcium imaging of neurons in sensory cortices revealed that E-SARE reporter expression correlates with sensory-evoked neuronal activity at the single-cell level and is highly specific to the type of stimuli presented to the animals. This activity-dependent promoter can expand the repertoire of genetic approaches for high-resolution anatomical and functional analysis of neural circuits.
authors.affiliation: Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawashima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitamura
authors.forename: Kanzo
authors.initials: K
authors.lastname: Suzuki
authors.forename: Mio
authors.initials: M
authors.lastname: Nonaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kamijo
authors.forename: Sayaka
authors.initials: S
authors.lastname: Takemoto-Kimura
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okuno
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohki
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Bito
mesh_terms: D000818:Animals; D001369:Axons; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005829:Geniculate Bodies / Q000166:cytology / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008967:Molecular Biology / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods; D009474:Neurons / Q000502:physiology*; D010775:Photic Stimulation; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements; D059010:Single-Cell Analysis / Q000379:methods; D014793:Visual Cortex / Q000166:cytology / Q000502:physiology
chemical_list: D049452:Green Fluorescent Proteins; C045073:Cre recombinase; D019426:Integrases; D002118:Calcium