Chemogenetics Flashcards

1
Q

What is chemogenetics?

A

Use unique (inert) ligands to activate engineered receptors.

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2
Q

What can we use chemogenetics for?

A

Can use this approach to reversibly alter function of neurons in circuits, and alter behaviour

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3
Q

What can neurotransmitters bind to?

A

Membrane receptors (GPCRs)

These activate signalling pathways and change neural activity

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4
Q

What is a common chemogenetic approach?

A

DREADDs

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5
Q

What does DREADD stand for?

A

Designer Receptors Exclusively Activated by Designer Drugs

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6
Q

What are DREADDs

A

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

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7
Q

What is the temporal scale of chemogenetics?

A

Slower than optogenetic lights
Drug can take hours to take effect

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8
Q

What are variants of DREADD

A

hM3Dq
hM4Di

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9
Q

How does hM3Dq work?

A
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10
Q

How does hM4Di work?

A
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11
Q

How are dreads similar to optogenetics?

A

Can both excite/inhibit neural activity

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12
Q

How are dreads different to optogenetics?

A
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13
Q

What is an issue with DREADDs?

A
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14
Q

How do we drive the expression of DREADDs?

A
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15
Q

What is the ligand for DREADD?

A

CNO

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16
Q

How can CNO be administered?

A
17
Q

What an assumption about CNO?

A

CNO when given systemically was assumed to cross the BBB

18
Q

What is the issue with this assumption?

A

Wasn’t actually crossing the BBB, it was binding

19
Q

How does this make us cautious?

A
20
Q

How can we control for this issue with CNO?

A
21
Q

What is the advantage of chemogenetics over optogenetics?

A

Doesnt need light or fibres

22
Q

What is a disadvantage compared to optogenetics?

A
23
Q

What was the first paper to combine in vivo Ca2+ measurements and fMRI?

A

Schulz et al. (2012)

24
Q

What did Schulz et al. (2012) find?

A

Demonstration that it was possible to simultaneously measure fMRI BOLD and cellular calcium responses to electrical paw stimulation in their set up

25
Q

What is an important consideration?

A

Air - filled spaces around inserted optic fibre with agar to compensate for this