Spectrally distinct channelrhodopsins for two-colour optogenetic peripheral nerve stimulation.

Technologies for peripheral nerve stimulation have conventionally relied on the anatomic placement of electrodes adjacent to subsets of sensory fibres or motor fibres that selectively target an end effector. Here, we demonstrate the use of optogenetics to directly target the innervating fibres of an end effector by relying on retrograde transfection of adeno-associated virus serotype 6 to restrict axonal opsin expression to the desired fibre targets. By using an in vivo screen in rats, we identify the first channelrhodopsins as well as a halorhodopsin that respond to red light in the peripheral nerve.

The Ewing Amputation: The First Human Implementation of the Agonist-Antagonist Myoneural Interface.

Background: The agonist-antagonist myoneural interface (AMI) comprises a surgical construct and neural control architecture designed to serve as a bidirectional interface, capable of reflecting proprioceptive sensation of prosthetic joint position, speed, and torque from and advanced limb prosthesis onto the central nervous system. The AMI surgical procedure has previously been vetted in animal models; we here present the surgical results of its translation to human subjects.

Methods: Modified unilateral below knee amputations were performed in the elective setting in 3 human subjects between July 2016 and April 2017.

A murine model of a novel surgical architecture for proprioceptive muscle feedback and its potential application to control of advanced limb prostheses.

Objective: Proprioceptive mechanisms play a critical role in both reflexive and volitional lower extremity control. Significant strides have been made in the development of bionic limbs that are capable of bi-directional communication with the peripheral nervous system, but none of these systems have been capable of providing physiologically-relevant muscle-based proprioceptive feedback through natural neural pathways. In this study, we present the agonist-antagonist myoneural interface (AMI), a surgical approach with the capacity to provide graded kinesthetic feedback from a prosthesis through mechanical activation of native mechanoreceptors within residual agonist-antagonist muscle pairs.

Transdermal optogenetic peripheral nerve stimulation.

Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks.

Approach: Here we report an alternative approach involving transdermal illumination.

Three-dimensional multiwaveguide probe array for light delivery to distributed brain circuits.

To deliver light to the brain for neuroscientific and neuroengineering applications like optogenetics, in which light is used to activate or silence neurons expressing specific photosensitive proteins, optical fibers are commonly used. However, an optical fiber is limited to delivering light to a single target within the 3D structure of the brain. Here, we describe the design and fabrication of an array of thin microwaveguides, which terminates at a three-dimensionally distributed set of points, appropriate for delivering light to targets distributed in a 3D pattern throughout the brain.

Towards optogenetic sensory replacement.

Over the last several years we have developed a rapidly-expanding suite of genetically-encoded reagents (e.g., ChR2, Halo, Arch, Mac, and others) that, when expressed in specific neuron types in the nervous system, enable their activities to be powerfully and precisely activated and silenced in response to light.

Multiwaveguide implantable probe for light delivery to sets of distributed brain targets.

Optical fibers are commonly inserted into living tissues such as the brain in order to deliver light to deep targets for neuroscientific and neuroengineering applications such as optogenetics, in which light is used to activate or silence neurons expressing specific photosensitive proteins. However, an optical fiber is limited to delivering light to a single target within the three-dimensional structure of the brain. We here demonstrate a multiwaveguide probe capable of independently delivering light to multiple targets along the probe axis, thus enabling versatile optical control of sets of distributed brain targets.