Photochemical Actuators

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Background

The idea of using light-sensitive molecular tools for the optical control of neuronal activity (actuators) had been latently present in the literature well before Crick articulated their theoretical utility in 1999 [1]. In particular, photochemistry had already provided insights into how to convert a ligand from an inert state into a high affinity form, a field which would become popular in neuroscience with the use of caged neurotransmitters [2]. Using this technique, synthetic photoconvertible ligands can be used to optically modulate neuronal activity through the activation of specific receptor proteins. To restrict the action of the ligand to genetically designated neurons, the receptor itself has to be targeted to these neurons [3]. This method was used by Lima and Miesenböck (2005) to elicit specific behaviors in fruit flies using light as a trigger, providing the first example of an optically “remote-controlled” animal.

The photoactivation process can be made more efficient by linking the ligand to the protein through a covalent bond and obtaining a photoswitched tethered ligand (PTL), a technique used successfully to control nicotinic receptors [4], ionotropic glutamate receptors [5], potassium channels [6, 7, 8] and recently a chimeric potassium-selective glutamate receptor called HyLighter [9]. One major drawback of photochemical approaches is the necessity of either delivering the ligand or conjugating the PTL to the target protein, which limits their use to easily accessible preparations like cultured neurons, brain slices or small organisms such as fruit flies or zebrafish larvae. Photochemical approaches to control neuronal firing have been reviewed by Gorostiza and Isacoff [10, 11] and by Miesenbock (2011).

Photochromic Ligands

Photochromic Tethered Ligands

[LiGluR] [12] HyLighter [9]

Available constructs

Name Description Map Lab Addgene


References

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  1. Error fetching PMID 10670022: [Crick1999]
  2. Error fetching PMID 8794086: [Nerbonne1996]
  3. Error fetching PMID 12540832: [Zemelman2003]
  4. Error fetching PMID 5288770: [Bartels1971]
  5. Error fetching PMID 16408092: [Volgraf2006]
  6. Error fetching PMID 15558062: [Banghart2004]
  7. Error fetching PMID 16870840: [Chambers2006]
  8. Error fetching PMID 21525363: [Fortin2011]
  9. Error fetching PMID 20581843: [Janovjak2010]
  10. Error fetching PMID 17882331: [Gorostiza2007]
  11. Error fetching PMID 18927384: [Gorostiza2008]
All Medline abstracts: PubMed HubMed