DREADD users blog

In 2015 there were 358 papers where DREADD technology played an important role.  I created a WORDLE using these and it looks like (no surprise) Neurons were used as frequent targets. My top picks for 2015: 1.   Chemogenetic  disconnection of monkey orbitofrontal and rhinal cortex reversibly disrupts reward value. Eldridge MA, Lerchner W, Saunders RC, Kaneko H, Krausz KW, Gonzalez FJ, Ji B, Higuchi M, Minamimoto T, Richmond BJ. Nat Neurosci . 2016 Jan;19(1):37-9. doi: 10.1038/nn.4192. Epub 2015 Dec 14. 2.   A New  DREADD  Facilitates the Multiplexed  Chemogenetic  Interrogation of Behavior. Vardy E, Robinson JE, Li C, Olsen RH, DiBerto JF, Giguere PM, Sassano FM, Huang XP, Zhu H, Urban DJ, White KL, Rittiner JE, Crowley NA, Pleil KE, Mazzone CM, Mosier PD, Song J, Kash TL, Malanga CJ, Krashes MJ, Roth BL. Neuron . 2015 May 20;86(4):936-46. doi: 10.1016/j.neuron.2015.03.065. Epub 2015 Apr 30 3.   The first structure-activity relationship studies for  designer   receptor

Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect of the sickness response reduces the quality of life for people suffering from chronic inflammatory diseases and is a nuisance during mild infections like common colds or the flu. To investigate how inflammation is perceived as unpleasant and causes negative affect, we used a behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced discomfort. Using a combination of cell-type–specific gene deletions, pharmacology, and chemogenetics, we found that systemic inflammation triggered aversion through MyD88-dependent activation of the brain endothelium followed by COX1-mediated cerebral prostaglandin E 2  (PGE 2 ) synthesis. Further, we showed that inflammation-induced PGE 2  targeted EP1 receptors on striatal dopamine D1 receptor–expressing neurons and that this signaling sequence induced aversion through GABA-mediated inhibition of dopamine

Cell Metabolism Advances in neuro-technology for mapping, manipulating, and monitoring molecularly defined cell types are rapidly advancing insight into neural circuits that regulate appetite. Here, we review these important tools and their applications in circuits that control food seeking and consumption. Technical capabilities provided by these tools establish a rigorous experimental framework for research into the neurobiology of hunger. Nicely balanced view of all the current technological approaches.

Another interesting paper from the Gutkind lab  

 Previous research has focused on feeding circuits residing in the hindbrain and midbrain that govern homeostatic or hedonic control of food intake. However, the feeding circuits controlling emotional or cognitive aspects of food intake are largely unknown. Here we use chemical genetics and optogenetic techniques to dissect appetite control circuits originating from ventral hippocampus (vHPC), a brain region implicated in emotion and cognition. We find that the vHPC projects functional glutamatergic synaptic inputs to the lateral septum (LS) and optogenetic activation of vHPC projections in LS reduces food intake. Consistently, food intake is suppressed by chemogenetic activation of glutamatergic neurons in the vHPC that project to the LS and inactivation of LS neurons blunts vHPC-induced suppression of feeding. Collectively, our results identify an anorexigenic neural circuit originating from vHPC to LS in the brain, revealing a potential therapeutic target for the treatment of ano

Here's the first of likely many of these papers --has some interesting proof-of-concept findings as well as caveats related to CNO in primates.  For those interested in DREADDs in primates you may find our new CNO analogues more useful.

Very cool and comprehensive paper ; again use chemogenetic not pharmacogenetic A single sub-anesthetic dose of ketamine exerts rapid and sustained antidepressant effects. Here, we examined the role of the ventral hippocampus (vHipp)-medial prefrontal cortex (mPFC) pathway in ketamine’s antidepressant response. Inactivation of the vHipp with lidocaine prevented the sustained, but not acute, antidepressant-like effect of ketamine as measured by the forced swim test (FST). Moreover, optogenetic as well as pharmacogenetic specific activation of the vHipp–mPFC pathway using DREADDs (designer receptors exclusively activated by designer drugs) mimicked the antidepressant-like response to ketamine; importantly, this was pathway specific, in that activation of a vHipp to nucleus accumbens circuit did not do this. Furthermore, optogenetic inactivation of the vHipp / mPFC pathway at the time of FST completely reversed ketamine’s antidepressant response. In addition, we found that a transient i