DREADD users blog

I get this question a lot and certainly there are a number of distinctions one can make with regard to these two technologies (Table 1). TABLE 1. COMPARISON OF CHEMO- AND OPTOGENETIC PLATFORMS IDEAL CRITERIA OPTOGENETIC CHEMOGENETIC Non-invasive No: Inherently invasive Yes: chemical actuators may be administered via drinking water Does not require specialized equipment No: Multi-channel programmable light source optic fibers, implantable light source. Yes:   routine laboratory equipment; chemical actuators commercially available Capable of multiplexing Yes: remarkable spectral diversity Yes : at least theoretically Neuronal subdomain-specific modulation Yes/ No: via excitation of opsins in axonal fibers; back-propagating action potentials reported. Yes : via local injections and subdomain specific targeting

I received an email the other day suggesting that some AAV-based DREADDs were not working 'as advertised'. To make a long email saga short it turns out that the Cre-driver line used had not been validated in the particular tissue being used. Thus the reason the DREADD was not being expressed is because there was no expression of Cre in the cells of interest. Here's what my lab does (and what we recommend) before using a Cre-line: Check the literature for expression in the tissue/cell type of interest Check the literature to see if any lab has ever used it to express a FLEX/DIO-based cargo in the cell type of interest If not, use a AAV-FLEX-XFP virus and do a control experiment to see if the experiment will work as advertised Alternatively use an Rosa6-FLOXED XFP reporter mouse If the controls do not work this would indicate: The Cre-line does not express sufficient Cre in the cell of interest There is something wrong with your technique Only after yo

For those who missed the webinar it is available here .

I will give a webinar on DREADD2.0 (updates and enhancements to DREADD technology) Wednesday (3/18/2015; 9 am PT) .  As in the past the presentation will be archived and available on Youtube. If you wish to see this in 'real time' go to the link above and register (it is free);  Q&A available during the talk.

Nice paper in Nature Neuroscience from Kash lab and colleagues--a lot of stuff here going from mice to primates.

A nice review on the use of chemo- and optogenetic technologies for seizure control in Nature Neuroscience .