L14 - Fixing Faulty Neural Circuits Flashcards
What are channelrhodopsin?
Unselective channel that transmits Na and K
When it opens the membrane depolarises
What are channelrhodopsins stimulated by?
Blue light
How was channelrhodopsins used in the mouse brain?
Expressed in the motor cortex
If brain stimulated by blue light the mouse moves a lot quicker and in opposite direction
What are halorhodopsins?
When it opens the membrane hyperpolarises
Can also be used in correction of the circularity
- E.g. used in epilepsy
What are halorhodopsins stimulated by?
Yellow light
What can be used instead of channelrhodopsins?
Small organic compounds
What is the benefit of the use of small organic compounds?
More specific
Contains a double bond and a part that binds an ion channel
What happens if light is used on small organic compounds?
The configuration changes
From straight chain (trans) to bent (cis)
- In trans configuration – molecule blocks the channel
- In cis configuration – molecule does not block the channel
How are GABA receptors photocontrolled?
Ligand for the receptor
In one configuration – ligand will bind and activate channel
In another configuration – ligand too far away from the binding site
GABA receptors are therefore activated in light
What other receptors can be photocontrolled?
Acetylcholine receptors
Potassium channels
Glutamate receptors
Either hyperpolarised or depolarised in response to light
What is Retinitis pigmentosa?
Occurs due to retinal degeneration
- Photoreceptors die
Visual field gradually becomes smaller and smaller
How could an artificial retina work?
Could use
- Light activated electrodes
- Don’t last very long
- Ganglion cells are the cells exposed to the electrodes
- Channel/halorodopsin
When is the retina most need to be stimulated?
For retinitis pigmentosa
When is the visual cortex most needed to be stimulated?
When the optic nerve didn’t develop or is destroyed
Why is it important to activate as early as possible in the visual pathway?
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
- E.g. motion sensitive RGC is active only when there is motion
What are the two ways ganglion cells can be artificially activated?
Electric stimulation
Channelrhodopsin and halorhodopsin
Only problem is that these stimulate ganglion cells not photoreceptors or bipolar cells
What are the two classes of ganglion cells?
Magnocellular
Parvocellular
These can respond to light in different colours
Direction selectivity is evident where?
In the retina
Responds to movements in some directions but not the others
Typically shown in ON/OFF cells
What is the hypercomplex in the visual cortex?
Respond only in a certain orientation
If the bar is slightly tilted after leaving the receptive field a response is once again seen
What is the solution to the activation of only ganglion cells by electrodes?
Use light to stimulate deeper layers - bipolar cells or even photoreceptors
In a cell with retinal degeneration with only small parts of the photoreceptor left (still formed synapses with bipolar cells) what was expressed in photoreceptors?
Halorhodopsin
Used yellow light to activate halorhodopsin not photoreceptors
In the cell with retinal degeneration how was it tested that the ganglion cells where intact?
ON cells spike with light
OFF cells spike when no light
Some function of the photoreceptors is restored
In the cell with retinal degeneration how was it tested that the centre surround organisation of ganglion cells was intact?
Further increasing the size of light spot decreases the response of the ganglion cell
In the cell with retinal degeneration how was it tested direction selectivity was intact?
Used moving spot of light
Showed null and preferred direction
Why is injection of small organic molecule in retinitis pigmentosa retina not as successful?
No specificity
Will activate mainly ganglion cells
