BMS248 Lecture 13 - Correction of faulty neural circuits

Question 1

What is a channelrhodopsin? What is it activated by? What happens when activated?

Answer 1

Non-selective ion channel activated by blue light (480nm) - depolarisation - activation

Question 2

When ChR is expressed in the motor cortex of a mouse what occurs?

Answer 2

When activated by light - mouse moves fast in circles

Question 3

What is a halorhodopsin? What is it activated by? What happens when activated?

Answer 3

Chloride ion selective channel activated by yellow light (570nm) - hyperpolarisation - blocks activity of neuron

Question 4

How do small organic compounds modify the activity of ion channels?

Answer 4

Light-induced cis-trans isomerism: small organic compounds change conformation depending on light
These are attached to proteins - so the conformation of the ion channel changes with light

Question 5

What property of GABA receptors means they can be under photo control

Answer 5

Double bond allows two different conformations - open/closed
Acetylcholine, potassium, and glutamate also under photocontrol as well as normal ligand binding

Question 6

What is Retinitis pigmentosa?

Answer 6

Progressive decrease in the field of view until a patient becomes blind - retinal degeneration
Genetic disease due to mutation

Question 7

What is lost in retinitis pigmentosa? What does this mean for bipolar cells?

Answer 7

Progressive decrease in number of photoreceptors - bipolar cells begin to degenerate as they don’t receive input from photoRs
Can artificially stimulate retina

Question 8

Why is it important to activate as early as anatomically possible in the visual pathway in regards to artificially activating the retina?

Answer 8

1. Retina performs complex computations
2. Ganglion cells - have different functions and project to different brain areas
3. Stimulation of RGC with simple stimuli is useless - e.g. motion sensitive RGC is active only when there is motion

Question 9

What are two ways to artificially activate the retina?

Answer 9

1. Electric stimulation - heat is an issue
2. Channelrhodopsin and Halorhodopsin - need to be delivered and expression in specific neurons

Question 10

What is the artificial retina and what does it activate?

Answer 10

Microelectrode array on retina activated by light - generates a current which stimulates the neurons
However it stimulates RGCs, NOT photoreceptors or bipolar cells

Question 11

Why is it a problem that the artificial retina activates RGCs?

Answer 11

Some RGCs are direction selective - respond to movement in some directions but not others - therefore will not respond when activated with a simple stimulus
Solution: use light to stimulate deeper layers - bipolar cells/photoRs

Question 12

What can be expressed in retinitis pigmentosa retina (instead of photoRs) and why

Answer 12

Halorhodopsin - because they hyperpolarise in response to light the same as photoRs

Question 13

What 3 functions of photoRs and RGCs are restored when halorhodopsin is expressed in photoRs?

Answer 13

1. Ability of photoRs to hyperpolarise in response to light
2. Centre-surround organisation of RGCs
3. Direction selectivity of RGCs

Question 14

What is the main excitatory NT?

Answer 14

Glutamate - depolarisation

Question 15

What is the main inhibitory NT?

Answer 15

GABA - hyperpolarisation

Question 16

What does epilepsy arise from?

Answer 16

Imbalances between excitatory and inhibitory neurotransmission
Mutations can disrupt this balance - leading to over excitation of neurons