10-ElectricalStimulationsOfNeurons

works well and for very long time

nerve-based electrode

• in / on / around peripheral nerve trunk

• directly stimulate peripheral nerve

muscle-based electrode

• in / on skeletal muscle

• stimulate terminal nerve fibers that activate muscle

tube of membrane, surrounded by myelin sheath:

• insulates the axon

• enhances signal conduction

myelin sheath regularly interrupted by exposed sections of membran: nodes of Ranvier

—> allow electrical signals to ‘jump’ from node to node

—> increases speed and efficiency of neural sinal transmission

change of membrane potential (ΔVm) due to an electrical field (E)

d = thickness of membrane (typically 7.5–10 nm)

E = strenght of electrical field

one side of membrane depolarizes

opposite side hyperpolarizes

membrane potenetial change:

E = strength of electric field

r = radius of axon

θ = angle btw electric field and position on axon

axon isolated with myelin sheaths, with nodes of Ranvier extracellular stimulating electrode generates elecrtical field

voltage at distance r:

electrical circuit representation: (Resistors and Capacitors)

Cm = membrane capacitance (storage of charge)

Rm = membrane resistance (to ion flow across membrane)

Ra = Axial Resistance (to ion flow along axon)

—> change of membrane potential locally -> depolarization / hyperpolarization -> signal propagation

• increases membrane resistance (Rm), reducing signal leakage

• decreases membrane capacitance (Cm), requiring less charge for depolarization

• enables saltatory conduction (action potentials ‘jump’ between nodes of Ranvier)

• Voltage (V) - potential difference along neuron due to external electric field

• First Derivative of Voltage - represents electric field (E)

  = spatial gradient of voltage

• Second Derivative of Voltage - Activation Function

  determines regions of de- and hyperpolarization in response to external electric field —> show where stimulation most effective

Anisotropy

differences in tissue condutctivity (gray matter vs. white matter) affect how electric field is distributed

Tissue type

inhomogenous tissues (gray and white matter) create non-uniform electric fields -> alter activation functions spatial distribution

• localizes effects of stimulation -> help targeting brain regions effectively

• ensures stimulation is optimized for therapy

cutting-edge technique

uses light to control neurons genetically modified to express light-sensitive proteins

-> allows precise manipulation of neuronal activity

• Electrical Stimulation - traditional method

  non-specific activation of nearby neurons -> simulatneous excitation and inhibition

• Optogenetic Excitation

  with light-sensitive ion channels, like channelrhodopsins

  blue light -> channels open -> Na+ flow in neuron

  —> depolarization and excitation

• Optogenetic Inhibition

  with light-sensitive protein, like halorhodopsins or archaeorhodopsins

  yellow or green light -> activates proteins -> Cl- flow in or H+ out of neuron

  —> hyperpolarization and inhibition

• Light source properties

  wavelength, intensity, beam focus

• Attenuation

  tissue absorption and scattering reduce photon deilvery to neurons

• Distance

  greater distances from light decrease photon flux

• optogenetics: targets only neurons genetically modified to express light-sensitive proteins

• electrical stimulation: acitvates all nearby -> unwanted side effects like excitation and inhibition

1. hø photon energy triggers from closed to open state

2. Open-state dynamics: transitions btw open states

3. light ends -> channels back to closed states via Recovery Paths (Gd1, Gd2, Gr)

channelrhodopsins = light-sensitive proteins genetically expressed in auditory neurons

when activated by light -> neuronal depolarization -> simulating natural auditory signals

LED

broad beam divergence (~120°) -> diffuse light that expands over distance

for stimulating larger neural regions where high precision no critical

—> more cost-effective and simpler but lack precision

VCSEL

narrow beam divergence (~16°) -> focused and precise light output

for precise, localized stimulation in optogenetics or applications requiring high spatial resolution

—> superior targeting but require careful alignment and more complex

+ increased precision with narrow light sources

+ more independent stimulation channels (up to 100)

+ temporal precision with fast opsin variants -> stimulation rates upt to 200 spikes/second

Challenges:

• narrow light sources and precise targeting required

• energy consumption significanltly higher

• fast opsin deactivation necessary to limit Na+ influx

• long-term stability is concerned

• implantation, stability and alignment need improvement