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Nat Methods. 2013 Sep;10(9):889-95. doi: 10.1038/nmeth.2559. Epub 2013 Jul 14.

Functional labeling of neurons and their projections using the synthetic activity-dependent promoter E-SARE.

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Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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  • Nat Methods. 2014 Feb;11(2):210.


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.

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