Tiny fibers open new windows into the brain

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A multifunctional flexible fiber that enables viral delivery, optical stimulation, and recording with one-step surgery. (credit: Seongjun Park et al./Nature Neuroscience)

Imagine a single flexible polymer fiber 200 micrometers across — about the width of a human hair — that can deliver a combination of optical, electrical, and chemical signals between different brain regions, with the softness and flexibility of brain tissue — allowing neuroscientists to leave implants in place and have them retain their functions over much longer periods than is currently possible with typical stiff, metallic fibers.

That’s what a team of MIT scientists has reported in the journal Nature Neuroscience. (Previous research efforts in neuroscience have generally relied on separate devices: needles to inject viral vectors for optogenetics, optical fibers for light delivery, and arrays of electrodes for recording, adding complication and the need for tricky alignments among the different devices.)

Multifunctional

For example, in tests with lab mice, the researchers were able to inject viral vectors that carried genes called opsins (which sensitize neurons to light) through one of two fluid channels in the fiber. They waited for the opsins to take effect, then sent a pulse of light through the optical waveguide in the center, and recorded the resulting neuronal activity, using six electrodes to pinpoint specific reactions. All of this was done through a single flexible fiber.

“It can deliver the virus [containing the opsins] straight to the cell, and then stimulate the response and record the activity — and [the fiber] is sufficiently small and biocompatible so it can be kept in for a long time,” says Polina Anikeeva, a professor in the MIT Department of Materials Science and Engineering.

Since each fiber is so small, “potentially, we could use many of them to observe different regions of activity,” she says. In their initial tests, the researchers placed probes in two different brain regions at once, varying which regions they used from one experiment to the next, and measuring how long it took for responses to travel between them.

The key ingredient that made this multifunctional fiber possible was the development of conductive “wires” that maintained the needed flexibility while also carrying electrical signals well. The team engineered a composite of conductive polyethylene doped with graphite flakes. The polyethylene was initially formed into layers, sprinkled with graphite flakes, then compressed; then another pair of layers was added and compressed, and then another, and so on.

The team aims to reduce the width of the fibers further, to make their properties even closer to those of the neural tissue and use material that is even softer to match the adjacent tissue.

The research team included members of MIT’s Research Laboratory of Electronics, Department of Electrical Engineering and Computer Science, McGovern Institute for Brain Research, Department of Chemical Engineering, and Department of Mechanical Engineering, as well as researchers at Tohuku University in Japan and Virginia Polytechnic Institute. It was supported by the National Institute of Neurological Disorders and Stroke, the National Science Foundation, the MIT Center for Materials Science and Engineering, the Center for Sensorimotor Neural Engineering, and the McGovern Institute for Brain Research.


Abstract of One-step optogenetics with multifunctional flexible polymer fibers

Optogenetic interrogation of neural pathways relies on delivery of light-sensitive opsins into tissue and subsequent optical illumination and electrical recording from the regions of interest. Despite the recent development of multifunctional neural probes, integration of these modalities in a single biocompatible platform remains a challenge. We developed a device composed of an optical waveguide, six electrodes and two microfluidic channels produced via fiber drawing. Our probes facilitated injections of viral vectors carrying opsin genes while providing collocated neural recording and optical stimulation. The miniature (<200 μm) footprint and modest weight (<0.5 g) of these probes allowed for multiple implantations into the mouse brain, which enabled opto-electrophysiological investigation of projections from the basolateral amygdala to the medial prefrontal cortex and ventral hippocampus during behavioral experiments. Fabricated solely from polymers and polymer composites, these flexible probes minimized tissue response to achieve chronic multimodal interrogation of brain circuits with high fidelity.

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