DREADD users blog

I'm frequently asked "Which is better, opto- or chemogenetics?" To which I'm tempted to reply:  "Which is better, red or green ?" Clearly, depends on the experiment and it is likely that there is a perfect (or nearly so) way to do it.  Sometimes this will be with light, other times with chemicals--sometimes neither. At any rate, here's a nice example of combining them to deconstruct interneuron activity and odorant in Nature Neurosciences " Neuronal pattern separation is thought to enable the brain to disambiguate sensory stimuli with overlapping features, thereby extracting valuable information. In the olfactory system, it remains unknown whether pattern separation acts as a driving force for sensory discrimination and the learning thereof. We found that overlapping odor-evoked input patterns to the mouse olfactory bulb (OB) were dynamically reformatted in the network on the timescale of a single breath, giving rise to separated patterns

Nice paper here in Neuron today as well as commentary . One of interesting tidbits (for me at least) was that apparently DREADD technology is so widely used that the authors no longer cite any papers (or reviews) to it as a technology--I guess this means anyone will know what they mean....

For reasons that are not entirely clear to me we are getting many requests for hM4Di and hM3Dq in lentiviral vectors. We will make what we have available via ADDGENE over the next couple of weeks.

A nice paper on the effect of food palatability and feeding as well as a nice independent replication of effects of KORD in Cell Metabolism

Interesting paper here:  " the chemogenetic reduction of cholinergic activity in freely behaving animals disrupted odor discrimination of simple odors, and the investigation of social odors associated with behaviors signaled by the Vomeronasal system."

"   We virally expressed inhibitory hM4Di designer receptor exclusively activated by a designer drug (DREADD) in dACC neurons, and examined the effects of this inhibitory action with the attention-based 5-choice serial reaction time task. DREADD inactivation of the dACC neurons during the task significantly increased omission and correct response latencies, indicating that the neuronal activities of dACC contribute to attention and processing speed. Selective inactivation of excitatory neurons in the dACC not only increased omission, but also decreased accuracy. The effect of inactivating dACC neurons was selective to attention as response control, motivation and locomotion remain normal. This finding suggests that dACC excitatory neurons play a principal role in modulating attention to task relevant stimuli. This study establishes a foundation to chemogenetically dissect specific cell-type and circuit mechanisms underlying attentional behaviors in a genetically tractable species

Nature, Trachtenberg lab GCaMP6-expressing PV neurons in vivo. and a nice image from a Neuron paper demonstrating same

I received an email last week asking if there was any evidence of this (other than readouts like cFos and bath application of CNO to slices). There is a nice paper in Nature 2015 ( Fig 4 ) using GCAMP as  a readout, here in Nature Communications using power-spectrum EEG as  a readout and in Neuron using single unit recordings in vivo. There are >100 papers citing use of hM4Di for this purpose in vivo but most (not surprisingly) look at slices to validate silencing/suppression of activity.