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. Author manuscript; available in PMC: 2009 Mar 13.
Published in final edited form as: Neuron. 2008 Mar 13;57(5):634–660. doi: 10.1016/j.neuron.2008.01.002

Table 2.

Genetically Targeted Methods for Inducible Inactivation of Neuronal Function

Method Model Systems Tested Inducible (Timescale) Reversible (Timescale) Target of Action Inducer Caveats References
Shibirets Dm minutes minutes ST temperature shift not applicable to mammals and birds Kitamoto, 2001
MIST Mm, MC, MBS tens of minutes hours ST small- molecule dimerizers some dimerizer drugs may have poor BBB penetration; expression levels need to be high Karpova et al., 2005
Allatostatin receptor/ Allatostatin R, F, M, Mm minutes minutes Vm, Rm peptide Allatostatin does not penetrate the BBB and needs to be applied locally Lechner et al., 2002; Gosgnach et al., 2006; Tan et al., 2006
Halorhodopsin MC, MBS, Ce milliseconds milliseconds Vm yellow light High expression levels and light intensities required Han and Boyden, 2007; Zhang et al., 2007
Rhodopsin-4 MC, Ch milliseconds tens of milliseconds ST, Vm, Rm blue light multiple nonspecific effects Li et al., 2005
GABAA-R/ zolpidem Mm, MBS minutes hours Vm, Rm small- molecule requires gamma-2 knockin mice and receptors containing α1–α3 subunits of the GABAA receptor Wulff et al., 2007
5-HT Receptor Mm hours hours Vm, Rm small- molecule limited to Htr1a knockout mice Tsetsenis et al., 2007
Inducible Expression of TeTxLc Mm days weeks ST small- molecule slow induction and reversal Sweeney et al., 1995; Yamamoto et al., 2003
Expression of K+ Channels MC days weeks Vm, Rm small- molecule slow induction and reversal; expression of K+ channels in vivo can have variable and paradoxical effects in the mammalian CNS Johns et al., 1999
GluCl/IVM Mm, MC tens of minutes hours to days Vm, Rm small- molecule the inducer drug is potentially toxic; slow reversibility Slimko et al., 2002; Lerchner et al., 2007
Expression of Tethered Toxins Zf NA NA Vm NA inducible expression has not been demonstrated Ibanez-Tallon et al., 2004

Abbreviations: Ce, C. elegans; Dm, Drosophila melanogaster; Zf, zebrafish; Ch, chick; M, monkey; Mm, mouse; R, rat; F, ferret; MC, mammalian cultured neurons; MBS, mammalian brain slices; BBB, blood-brain barrier; Vm, membrane potential; Rm, membrane resistance; ST, synaptic transmission.