Figure: Implantable Sensor Transmitter (IST, A3036B). At full power, delivers 15 mA to its ILED.
Optogenetics permits the stimulation of specific populations of neurons. Our implantable stimulators allow this optogenetic stimulation to take place in freely-moving mice. Our implatable stimulators are battery-powered, encapsulated, radio-controlled, fully wireless devices that we connect to implantable light sources for optogenetic stimulation. The same stimulators can be used for electrical stimulation, but here we consider only their optogenetic application. Our first Implantable Stimulator-Transponders (ISTs) were the A3036B Family of devices. We present results obtained with the A3036B in the sections below. The A3036 has since been replaced by the A3041. All our ISTs provide stimulation, command acknowledgements, battery monitoring, and a stimulus synchronizing signal, all by radio control and radio telemetry.
The implanatable light sources that can be coupled with the IST are the Surface-Mount Light-Emitting Diode (SMLED), and the Fiber-Coupled Light-Emitting Diode(FCLED).
The Fiber-Coupled Light-Emitting Diode (FCLED) is the SMLED with a tapered fiber placed directly on tothe LED. The fiber is 4 mm long, with a diameter of 270 μm.
The SMLEDs do not require a hole to be drilled through the skull. We can invoke optogenetic response with a less invasive procedure and be more certain we have not damaged brain tissue with our surgery. The FCLEDs are far more effective at delivering light to the light-sensitive brain tissue. Where we need 3-ms flashes at 10 Hz from an SMLED to invoke optogenetic response, we need only 1-ms flashes from an FCLED in the same type of animal. This is despite the fact that the SMLED emits three times as much optical power as the tip of the FCLED at the same LED current.
In order to validate our technology, we have identified two optogenetic stimulations which should induce distinct behavioral phenotypes. The first identifiable phenotype is circling behavioral. The second phenotype is seizure-like acticity. In order to induce these distinct behavioral phenotypes, we injected ChR2 into the motor cortex of six mice. We implanted our devices and administered light at varying pulses lengths, frequencies, and durations. In order to confirm the behavior was indeed due to abnormal brain activity, we implanted alongside our stimulator a two-channel Subcutaneous Transmitter (SCT, A3049W2Z) to monitor local field potential (LFP) with depth electrodes in both the motor and visual cortex. These two-channel transmitters provided bandwidth 0.0-80 Hz and were connected to solder-free, crimp-contact depth electrodes to reduce low-frequency artifact.
August 8th, 2021, Animal 6, Trial 6. Optogentic stimulus delivered by 270 μm × 4 mm fiber-coupled blue LED coupled with the Implantable Stimultor-Transponder (IST, A3036B). Lamp current 15 mA, optical power at fiber tip 4.2 mW. Local field potential recorded by two-channel 0.0-80 Hz Subcutaneous Transmitter (SCT, A3049W2Z).
 Figure: Intrinsic flourescent image of ChR2 expressing neurons in the right motor cortex of Animal Two. |
 Video: Animal Two Response to 1-ms pulses of 4.2-mW blue light at 10 Hz for 90 s. |
August 3rd, 2021, Animal 2, Trial 4. Optogentic stimulus delivered by 270 μm × 4 mm fiber-coupled blue LED coupled with the Implantable Stimultor-Transponder (IST, A3036B). Lamp current 15 mA, optical power at fiber tip 4.2 mW. Local field potential recorded by two-channel 0.0-80 Hz Subcutaneous Transmitter (SCT, A3049W2Z).
 Figure: Intrinsic flourescent image of ChR2 expressing neurons in the right motor cortex of Animal Six. |
 Video: Animal Six Response to 1-ms pulses of 4.2-mW blue light at 10 Hz for 90s. |
