Chemogenetics Flashcards
What is chemogenetics?
Use unique (inert) ligands to activate engineered receptors.
What can we use chemogenetics for?
Can use this approach to reversibly alter function of neurons in circuits, and alter behaviour
What can neurotransmitters bind to?
Membrane receptors (GPCRs)
These activate signalling pathways and change neural activity
What is a common chemogenetic approach?
DREADDs
What does DREADD stand for?
Designer Receptors Exclusively Activated by Designer Drugs
What are DREADDs
Receptors are engineered to interact with pharmacologically inert ligand (designer drug), no longer activated by neurotransmitters
Administration of the designer drug allows non-invasive control of function of cells, so you can give this drug orally or in water without invasive approaches
Cell-type specific expression of the exogenous receptor- drug is designed not to activate other receptors and the drug doesnt get activated by endogenous neurotransmitters e.g. dopamine so it means it has great cell specificity
What is the temporal scale of chemogenetics?
Slower than optogenetic lights
Drug can take hours to take effect
What are variants of DREADD
hM3Dq
hM4Di
How does hM3Dq work?
How does hM4Di work?
How are dreads similar to optogenetics?
Can both excite/inhibit neural activity
How are dreads different to optogenetics?
What is an issue with DREADDs?
How do we drive the expression of DREADDs?
What is the ligand for DREADD?
CNO
How can CNO be administered?
What an assumption about CNO?
CNO when given systemically was assumed to cross the BBB
What is the issue with this assumption?
Wasn’t actually crossing the BBB, it was binding
How does this make us cautious?
How can we control for this issue with CNO?
What is the advantage of chemogenetics over optogenetics?
Doesnt need light or fibres
What is a disadvantage compared to optogenetics?
What was the first paper to combine in vivo Ca2+ measurements and fMRI?
Schulz et al. (2012)
What did Schulz et al. (2012) find?
Demonstration that it was possible to simultaneously measure fMRI BOLD and cellular calcium responses to electrical paw stimulation in their set up
What is an important consideration?
Air - filled spaces around inserted optic fibre with agar to compensate for this