Correction of Faulty Neural Circuits

Question 1

How does channelrhodopsin work? (2)

Answer 1

• Non-selective cation channel activated by 460nm wavelength blue light
• Channel opens = cations into the neuron = depolarisation of the neuron

Question 2

How does halorhodopsin work? (2)

Answer 2

• Chloride channel activated by 570nm wavelength yellow light
• Channel opens = Cl- into the neuron = hyperpolarisation of the neuron

Question 3

How can small organic molecules be used to manipulate neurons instead of channelrhodopsin/halorhodopsin? (3)

Answer 3

• Use small molecules containing double bonds which can change cis/ trans conformation when light is shone on them
• Molecule can block an ion channel when in one conformation and dissociates when in the other conformation
• Light-induced isomerisation

Question 4

What is retinitis pigmentosa?

Answer 4

Degeneration of the retina which progressively decreases the field of view and leads to blindness

Question 5

Which parts of the brain could you artificially stimulate to restore vision in retinitis pigmentosa? (2)

Answer 5

• Retina
• V1 cortex if there is damage to the optic nerve

Question 6

Why is it important to activate as anatomically early in the visual pathway as possible? (3)

Answer 6

• The retina performs complex computations
• Different ganglion cells have different functions and project to different brain areas
• Stimulation of retinal ganglion cells with simple stimuli is useless

Question 7

How could you artificially activate the brain? (2)

Answer 7

• Electrical stimulation
• Channelrhodopsin and halorhodopsin

Question 8

What are the disadvantages of using electrical stimulation of the brain to restore vision? (2)

Answer 8

• Electrodes heat up when you stimulate them which eventually kills the neuron
• Wouldn’t work for restoring vision which would require electrodes to work every day for the duration of a patient’s life

Question 9

What are the disadvantages of using channelrhodopsin and halorhodopsin to restore vision? (2)

Answer 9

• Need to somehow deliver the channel genes into specific neurons
• Need to implant light guides which heat up when used

Question 10

Which cells would you need to stimulate with electrodes for an artificial retina? (2)

Answer 10

• The photoreceptors or bipolar cells not the retinal ganglion cells
• Problem because the retinal ganglion cells cover the photoreceptors and bipolar cells

Question 11

What are the 2 types of ganglion cells?

Answer 11

• Parvocellular
• Magnocellular

Question 12

How was vision restored in a mouse model for retinitis pigmentosa? (2)

Answer 12

• Express halorhodopsin in what is left of the photoreceptors
• Restored the activity of the on/off ganglion cells, the centre-surround organisation of ganglion cells and the direction selective cells

Question 13

Why would you express halorhodopsin in photoreceptors over channelrhodopsin?

Answer 13

Photoreceptors hyperpolarise in response to light so this is mimicked by halorhodopsin which causes hyperpolarisation

Question 14

How could seizures be controlled using optogenetics? (2)

Answer 14

• Express halorhodopsin in excitatory neurons/express channelrhodopsin in inhibitory neurons and activate these just before the seizure starts
• Inject a virus expressing optogenetic tools into the area of the brain where the seizures originate

Question 15

What are the problems with using optogenetics for epilepsy? (6)

Answer 15

• Large brain size and many areas are deep within the brain
• Need to know the seizure origin for each individual patient
• Need to express the optogenetic tools in specific neurons
• Decide whether to target excitatory or inhibitory neurons
• Problems associated with chronic light implants
• Need to detect the seizure before it starts