Figure: A3036B Implantable Sensor Transmitter (IST). 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 series of devices. Here we present results obtained with the A3036B, but the A3036 devices have since been replaced by the A3041 Implantable Stimulator-Transponders. 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 Clear-Epoxy Implantable Light-Emitting Diode (CE-ILED), Blunt-Fiber Light-Emitting Diode (BFLED) and the Tapered-Fiber Implantable Light-Emitting Diode (TF-ILED).
The Tapered-Fiber Implantable Light-Emitting Diode (TF-ILED) is an LED with an optical fiber placed directly on the LED. The end of the fiber is tapered to a point. In these experiments, the fiber is 4 mm long, with a diameter of 270 μm.
When deployed in a mouse, the CE-ILEDs do not require a hole to be drilled through the skull. Their light intensity is strong enough that they can shine through the thin skull of the mouse and provoke optogenetic response. We can invoke optogenetic response with a less invasive procedure and be more certain we have not damaged brain tissue with our surgery. The TF-ILEDs are far more effective at delivering light to the light-sensitive brain tissue. Where we need 3-ms flashes at 10 Hz from an CE-ILED to invoke optogenetic response, we need only 1-ms flashes from an TF-ILED in the same type of animal. This is despite the fact that the CE-ILED emits three times as much optical power as the tip of the TF-ILED 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 A3049W2Z Subcutaneous Transmitter (SCT) 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 blue Tapered-Fiber Implantable Light-Emitting Diode (TF-ILED) coupled with an A3036B Implantable Stimultor-Transponder (IST). Lamp current 15 mA, optical power at fiber tip 4.2 mW. Local field potential recorded by two-channel 0.0-80 Hz A3049W2Z Subcutaneous Transmitter (SCT).
 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 blue TF-ILED with an A3036B Implantable Stimultor-Transponder (IST). Lamp current 15 mA, optical power at fiber tip 4.2 mW. Local field potential recorded by two-channel 0.0-80 Hz A3049W2Z Subcutaneous Transmitter (SCT).
 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. |
