Remember DREADDs (Designer Receptors Activated Exclusively by Designer Drugs)? They’re one of the cooler technologies out there for neuroscientists. As a quick reminder, DREADDS are special receptors that respond to only a synthetic ligand (i.e. designer drug). The DNA for these receptors is inserted is transduced into a neuron, that neuron will begin to express that receptor. When the designer drug is introduced it activates only that receptor, either exciting or inhibiting the neuron without affecting other cells.
The image above is from a paper demonstrating a super neat use of this technique. Here’s the quick a dirty explanation. Scientists use viruses to edit a cells DNA, causing it to express the DREADD. They inject the viral vector into a brain region, and all the cells near the injection site is infected and begins expressing the DREADD. They can also use a virus that infects a neuron through its axon, functioning as a retrograde tracer. The virus travels up the axon and into the cell body. Now, imagine what happens if you inject that virus into a particular region. It will infect the cell bodies of that region, but it will also infect all the neurons that connect to that region. What the authors of the the above paper did was attach the gene for a particular enzyme to the virus used as a retrograde tracer. They also constructed a DREADD that wouldn’t be expressed correctly if that enzyme wasn’t also in the cell. They injected the DREADD virus into region A, and the enzyme virus into region B. Now, all the cells that start at region A, and send signals to region B, are infected with both the enzyme virus and the DREADD virus. These are the only cells with a functioning DREADD. Introducing the designer drug now only affects those cells that are infected with both viruses. This allows for very fine study of connections between brain regions.
This paper does a great job of illustrating this technique’s use by proposing using it to study the lateral habenula. Those who have trouble understanding the first paper (including me) should definitely read the latter at the very least.
