L19 - Sensory - Motor Integration (REWATCH THIS LECTURE)

Question 1

What is optogenetics?

Answer 1

The use of light to control cell s in living tissue (neurons) that have been genetically modified to express light sensitive ion channels.

Question 2

Advantages and disadvantages/caveats of Optogenetics

Answer 2

ADV

1) Genetically defined (promoter controlled) targeting specific neuronal sub-types
2) Temporal precision
3) Bimodal - the same or diff neurons can be excited or inhibited if both types of proteins are expressed by neurons

DIS

1) Invasive - optic fibre probe
2) Imperfect targeting
3) Bulk illumination = synchrous discharge
3) Stim and inhib go beyond normal phys ranges

Question 3

Blue light excit or inhib

Answer 3

Excit

Question 4

Difference between human type 2 opsin and bacterial type 1 opsin

Answer 4

Human
11-cis retinal -> all trrans retinal
GPCR

Bacterial
All trans retinal -> 13-cis retinal
Ion channels (Rhodopsin protein is the ion channel)

Question 5

OPSINS AS CHANNELS

• Baceriorhodopsin
• Halorhodopsin
• Channelrhodopsin

Answer 5

1) Bacterio- H+ from intra to extra
2) Halo - Cl from extra to intra
3) Channel - All ions in both directions

Question 6

Results - in normal vs parkinsonian mouse

Answer 6

Normal mice

• Bilateral excitation of indirect pathway MSNs = parkinsonia state (increase freezing, bradykinesia, decreased locomotor initiations)
• Direct pathway (decrease parkinsonian state)

Parkinsonian mouse
-Direct pathway - decreased parkinsonian state

Question 7

Implications of results

Answer 7

Dual pathways model validated

Capacity to selectively and precisely modulate the pathways offer a therapeutic approach not dependent on SN projections