Table 2.
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.