DREADD 2.0 Controls Brain Circuitry and Behavior

Brain connections
Brain connections
The new tool is some of the first research to come out of the BRAIN Initiative.

Neuroscientists working under the BRAIN Initiative have perfected a chemical-genetic remote control that can switch neurons and their associated behaviors on and off in mice. Being able to control these neurons will allow researchers to decode complex behaviors.

The tool, dubbed DREADD (Designer Receptors Exclusively Activated by Designer Drugs), was developed by Bryan Roth, MD, PhD, of the University of North Carolina, and colleagues over a decade ago, and now a second iteration, DREADD 2.0, improves on that original technology by introducing a synthetic brain chemical messenger system that integrates with naturally-occurring systems.

“With its new push-pull control, this tool sharpens the cutting edge of research aimed at improving our understanding of brain circuit disorders, such as schizophrenia and addictive behaviors,” NIH director Francis S. Collins, MD, PhD, said in a news release.

Roth, along with Michael Krashes, PhD, of the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, and colleagues genetically engineered mice with brains containing “designer receptors” in specific circuits. The synthetic proteins on the surface of neurons can only be activated by a coordinating synthetic chemical. When the “designer drug” bind to the receptor, it either triggers or blocks neuronal activity, allowing researchers to have control over the mice’s brain circuits and behaviors.

Advances in the second iteration of DREADD allow for bidirectional control, for instance controlling an animal’s movement and feeding behavior, which can last about an hour, while earlier versions of DREADD only allowed researchers to control activity in one direction, on or off.

The minimally-invasive tool’s prolonged effects will likely make it an important component in studies that require longer control of circuitry and behavior. 

A study documenting the use of the second-generation tool was published in Neuron


  1. Vardy E et al. Neuron. 2015; doi:10.1016/j.neuron.2015.03.065.
  2. NIH News Release