Download Neural Stimulation from an Implantable Optogenetics System

Neural Stimulation from an Implantable Optogenetics System
Fu-yu B. Chen, David M. Budgett, Simon Malpas, Daniel McCormick, Peter S. Freestone, The University of Auckland, New Zealand
Results
Design Concept
Optical Power Regulation
Optogenetics uses light to manipulate neural
activity with millisecond precision1.
Placing the light source and electronics in rat
abdomen and delivering light to deep brain via
optical fibre.
• LED Optical power can be regulated by (a)
current or (b) Pulse-Width Modulation (PWM).
It involves transfecting targeted cells with opsin
(photosensitive protein) and exciting/silencing
them with pulses of visible light.
Optical
Fiber
Brain
Advantages:
Targeted Cells
• Specific cell-type targeting
Neuron
• Simultaneous stimulation
Optogenetic Stimulation
Configurator
• PWM easily implemented in microprocessor, a
huge advantage for implantation.
• PWM technique: at high frequency, the amount
of photons emitted can be perceived as an
integration of the pulses.
Photocurrents evoked by a series of optical power
levels with 4ms light pulse using (a) DC voltage
and (b) PWM technique
(a)
Photocurrent (pA)
Introduction
Rat Brain
Optical Fibre
• We want to validate whether PWM can achieve
equivalent light stimulation as DC voltage
regulation.
• Harmless to tissue
EMG Signals
Sensing
Clinical Applications2:
(b)
100
50
0
-50
-100
-150
-200
-250
-300
-350
-400
200μW
150μW
100μW
75μW
60μW
50μW
0
10
20
30
40
50
60
70
80
90
100 110 120 130
Time (ms)
100
50
Rat Abdomen
Telemeter
x photons
Opsin
• Activating heart muscle
DC Voltage
• Restoring hearing
Vs
Photocurrent (pA)
0
• Parkinson’s Disease3, Epilepsy
50% x photons
1/2Vs
Equivalent
Wireless Power Transfer
State-of-the-art:
Vs
(A) Bench-top fibre-optic system – readily
available4
• Small for implantation in rat.
(B) Wirelessly powered device
(C) Integrate μLEDs in neuro-probe5
• Low heat dissipation.
100% Duty Cycle PWM
• Robust and precise light delivery.
• Remote control of light stimulation.
(A)
Light Generation & Delivery
(B)
(C)
Light source: 280μm x 280μm Blue (465nm)
LED – suitable for activating ChR2 expressed
neuron.
Light delivery: a 200μm (core) optical fibre.
Prototype:
Telemeter LED Light Module
Optical Fibre
150μW
100μW
-200
75μW
-250
60μW
-300
50μW
-350
10
20
30
40
50
60 70 80
Time (ms)
90
100 110 120 130
Both DC voltage and PWM techniques evoked equal
drops in photocurrent for a given reduction in
power.
p
Vs
Design considerations:
New approaches:
200μW
-150
0
Vs
PWM
-50
-100
50% Duty Cycle PWM
Mouse Brain Slices Validation
Experiment
To validate our implantable optogenetics system,
whole-cell recordings of neuron from transgenic
mouse brain slices using photocurrent patch
clamp was performed.
Intention:
Conclusion
• Show LED light source is able to evoke
photocurrent response
• PWM is a good technique to regulate optical
power
Optical Fibre
Pipette
Manipulator
Our LED optogenetics system is implantable:
• Small and robust light delivery system.
• Sufficient optical power to evoke photocurrent in
neuron with low power consumption.
• PWM is a feasible method for controlling light
power.
References
Neuron
Aim of this Study
Eliminate risk of infection by implementing a fully
implantable optogenetics stimulation system for
chronic studies.
• Optical power at the tip of fibre is 100μW –
sufficient to activate a ChR2 expressed neuron.
• Light module power consumption is 6.4mW.
Live Brain Slice
Optical Fibre
Pipette
1. E. S. Boyden, et al., "Millisecond-timescale, genetically targeted optical control of
neural activity," Nat Neurosci, vol. 8, pp. 1263-1268, 2005.
2. Lamballais, S. (2013). Optogenetics and its Applications in Psychology: Manipulating
the Brain Using Light. Journal of European Psychology Students, 4(1), 87-100.
3. Gradinaru, et al., "Optical Deconstruction of Parkinsonian Neural Circuitry," Science,
vol. 324, pp. 354-359, April 17, 2009 2009.
4. http://www.thorlabs.com/
5. T.-i. Kim, et al., "Injectable, Cellular-Scale Optoelectronics with Applications for
Wireless Optogenetics," Science, vol. 340, pp. 211-216, April 12, 2013 2013