Neuromodulation Techniques

Question 1

Compare and contrast electrical and optogenetic stimulation?

Answer 1

Electrical stimulation (ES):
- use of electrodes (nerve cuffs) to stimulate the CNS
- never cuffs contain strain sensor (allows electrode to grow with mice specimen)

Optogenetic Stimulation (OS):
opto –> light
genetic –> genes

express opsin genes to sensitize a group of cells to light
- able to excite / inhibit cells via diff wavelengths of light

Question 2

Compare and contrast electrical and optical stimulation shortcomings

Answer 2

Shortcomings of ES:
- stimulates neighboring tissue
- desensitization
- muscle fatigue
- invasive delivery (most of the time)

Shortcomings of optogenetic stimulation:
- use of transgenes (transfer opsin genes into organisms)
- heating (mitigate heat via pulsating light)
- light delivery tools (ensure that light can penetrate tissue at the right intensity)

Question 3

What are some advantages of optical stimulation over electrical stimulation (3)

Answer 3

1. specificity
2. controllability and reduced fatigue
   - reduced fatigue how? (specificty plays a role in ensuring that only specific motor units are activated and not the neighboring muscles)
3. less sensitive to simulator’s location (generate less inflammatory responses)

Question 4

Examples of electrical stimulation (4)

Answer 4

(invasive)
- cochlear implants
- pacemakers
- epidural stimulation
- retinal ganglion cell stimulation
- auditory brainstem implants

(non-invasive)
- deep brain stimulation via interference fields

Question 5

How can optical modulation be less invasive?

Answer 5

1. Increase depth of actuation
   - adopt infrared light for its higher penetration
   - modify optsin to operate at lower intensity thresholds
2. alternatives to transgenes
   - use photoswitchable molecules to reversibly sensitize cells to respond to light
   - generate heat to change the membrane capacitance of excitable cells
   - use thermally-responsive ion channels

Question 6

What is chemogentics (adv + disadv)

Answer 6

Engineer proteins to be recognized / respond to target molecules

Adv:
- doesn’t need a hardware which would disturb behavioral studies

Disadv:
- slow kinetics
- low spatial resolution (side effects)
- low temporal resolution (can’t control time or length of stimulation)

Question 7

What is acoustic stimulation? (adv + disadv)

Answer 7

(ultrasound is a type of acoustic stimulation)

sound waves that penetrate soft tissue and organs but are scattered / absorbed by hard tissues (bones)
- used to actuate mechano- / thermal responsive ion channels (LIFU in pulsed mode –> mechanical cell modulation)

Adv:
- higher penetration depth than light or electricity

disadv:
- low resolution (inversely proportional to penetration)
- non-specific
- tissue dmg / inflammation
- heating (HIFU –> cancer therapy)

Question 8

What are nanomaterials (modulation techniques) (adv + disadv)

Answer 8

alternative to implants and transgenes
- modulate nanomaterials outside of the body instead of modulating proteins / cells in the body

Adv:
- specificity (same size as proteins / DNA)
- variety in modulation (optical, mechano-, magnetism)
- unlimited depth penetration (due to magnetic field)

ex.
- mechanically open channels using MNDs under magnetic field
- MNDs absorb heat to activate heat-sensitive ion channels in adrenal gland

disadv:
- toxicity due to nanomaterials leakage (difficult to control where it goes after its been flushed away –> could accumulate in one specific area)
- protein coronas (coating of biological proteins around the nanomaterials)