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Genetic control of neuronal activity in mice conditionally expressing TRPV1


Here we describe a knock-in mouse model for Cre-loxP–based conditional expression of TRPV1 in central nervous system neurons. Expression of Cre recombinase using biolistics, lentivirus or genetic intercrosses triggered heterologous expression of TRPV1 in a cell-specific manner. Application of the TRPV1 ligand capsaicin induced strong inward currents, triggered action potentials and activated stereotyped behaviors, allowing cell type–specific chemical genetic control of neuronal activity in vitro and in vivo.

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Figure 1: Conditional expression of TRPV1 by Cre recombinase.
Figure 2: Conditional neuronal expression of TRPV1-IRES-ECFP in vivo by genetic intercross with mice harboring the nestin-Cre driver.
Figure 3: In vivo activation of neurons that conditionally express TRPV1.

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We thank D. Julius (University of California, San Francisco) for the rat Trpv1X cDNA, F. Wang for sharing both space and embryonic stem cell culture reagents, J. Gross for technical assistance, and Y. Ben-Shaul, I. Davison, C. Hanus, T. Helton, J. Hernandez, M. Kennedy, R. Mooney and J. Yi for helpful input and critical review of the manuscript. This work was supported by grants from the US National Institutes of Health (to M.D.E.). M.D.E. is an Investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations



B.R.A. designed experiments, generated and characterized knock-in mice, conducted electrophysiological and behavioral experiments, and wrote the paper. M.E.K. generated lentivirus. I.G.D. helped design and conduct electrophysiological experiments. L.C.K. participated in initial experimental design. M.D.E. designed experiments and wrote the manuscript.

Corresponding author

Correspondence to Michael D Ehlers.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7, Supplementary Methods (PDF 1179 kb)

Supplementary Movie 1

Capsaicin-mediated neuronal activation modifies behavior in awake behaving mice conditionally expressing TRPV1. Shown is the behavioral response of a nestin-Cre::ROSA-stopflox-TRPV1-IRES-ECFP mouse that was infused with 500 nM capsaicin via a cannula implanted in the dorsal left striatum. The movie shows representative activity prior to, 5 min after, and 15 min after capsaicin treatment. Mice fully recovered by 15 min post-infusion. (MOV 1072 kb)

Supplementary Movie 2

Capsaicin infusion does not affect locomotor behavior in control mice. Shown is the normal locomotor behavior before and after capsaicin infusion in ROSA-stopflox-TRPV1-IRES-ECFP control animals lacking Cre expression. (MOV 620 kb)

Supplementary Movie 3

Focal expression of TRPV1 unilaterally in the striatum results in contralateral circling behavior upon infusion with capsaicin. Shown is the behavioral response from a ROSA-stopflox-TRPV1-IRES-ECFP mouse locally infected in the right striatum with a YFP-IRES-Cre expressing lentivirus following infusion with 500 nM capsaicin 1 week post-infection. (MOV 1055 kb)

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Arenkiel, B., Klein, M., Davison, I. et al. Genetic control of neuronal activity in mice conditionally expressing TRPV1. Nat Methods 5, 299–302 (2008).

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