Though we discovered this some time ago , there has been lingering controversy regarding it's mechanism of action in humans. Here is a controlled study consistent with k-opioid being essential target.
On-line here . A fair amount of time was spent on this to make sure key issues were addressed --especially those which may not be obvious to those who do not study GPCRs. BTW: DREADDs are engineered GPCRs......
This will be useful for determining how and to what extent canonical (G protein) vs non-canonical (arrestin) singaling is essential for the actions of a particular biological/physiological phenomenon.
A nice paper just published using the M1-DREADD which like M3 is Gq coupled to interrogate learning and memory. As predicted M1 behaves similarly to M3.
Several of these papers have been appearing the past few days--my guess is reviewers who are fans of one technology or the other require that both be used. At any rate here is the key figure from a paper on-line in Nature today . Nice to see all the relevant controls....in addition to citing the original DREADD paper (which sadly few do).
Frequently am asked whether anyone has actually seen neurons 'silenced in vivo' via hM4Di. Here is the relevant data from a paper just out in PNAS . It shows a great example of how chemogenetics can provide the killer experiment when linked with in vivo neuronal imaging of neuronal activity.
Occasionally we get emails from users regarding AAV serotypes/lots which they believe are problematic. We normally forward these to the UNC vector core but would greatly appreciate having a 'running total' of those lots/serotypes/constructs which are problematic. That way we can take that information back to the vector core and help them to institute rigorous (and recommended) quality control above and beyond what they typically do. So here's what you should do: Simply reply to this listing the AAV lot/serotype/construct which works as expected or which does not work as expected. Example: Lot#666/8/ DEADDREADD : works fine--all cells exploded upon contact with CNO as predicted.