Nanotechnology tools for neuroscience and brain activity mapping

(Nanowerk Spotlight) A comprehensive understanding of the brain remains an elusive, distant frontier. To arrive at a general theory of brain function would be an historic event, comparable to inferring quantum theory from huge sets of complex spectra and inferring evolutionary theory from vast biological field work. You might have heard about the proposed Brain Activity Map – a project that, like the Human Genome Project, will tap the hive mind of experts to make headway in the understanding of the field. Engineers and nanotechnologists will be needed to help build ever smaller devices for measuring the activity of individual neurons and, later, to control how those neurons function. Computer scientists will be called upon to develop methods for storing and analyzing the vast quantities of imaging and physiological data, and for creating virtual models for studying brain function. Neuroscientists will provide critical biological expertise to guide the research and interpret the results.
The Brain Activity Map project has three goals in terms of building tools for neuroscience capable of 1) measuring the activity of large sets of neurons in complex brain circuits, 2) computationally analyzing and modeling these brain circuits, and 3) testing these models by manipulating the activities of chosen sets of neurons in these brain circuits.
Neuroscientists will require new tools both to study neurons and neural circuits with minimal perturbation and to study the human brain. These tools might include “smart”, active nanoscale devices embedded within the brain that report on neural circuit activity wirelessly and/or entirely new modalities of remote sensing of neural circuit dynamics from outside the body. Remarkable advances in nanoscience and nanotechnology thus have key roles to play in transduction, reporting, power, and communications.
An article in the March 20, 2013 online edition of ACS Nano ("Nanotools for Neuroscience and Brain Activity Mapping"), neuroscientists and nanoscientists discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience.
In light of the advances in resolution of top-down and bottom-up nanofabrication strategies, the endeavor toward matching the sizes of devices that measure and control neuronal activity with the sizes of individual neurons is compelling and appears inevitable. In their article, the authors enumerate a few of the areas in which they anticipate these contributions:
Electrophysiology – The major obstacles that presently limit the use of nanoscale probes are the engineering challenges of building efficient power and communications systems to interface such neural probes with the outside world and at the same time avoid tissue damage and undesirable cell responses.
Brain activity mapping with nanofabricated electrode arrays – Innovations in microelectrode manufacturing techniques have made it possible to deploy simultaneously nearly 1000 measurement sites distributed across several cortical areas of the same animal, allowing the firing patterns of hundreds of neurons to be monitored in parallel. Leveraging micro- and nanofabrication technology raises the prospect for creating vastly greater numbers of electrodes and smaller, less invasive implantable devices.
Advantages and challenges of electrode-array-based mapping approaches – New developments in nano-bio interfacing and 3D microfabrication techniques might provide the means to overcome some of the limitations of planar microelectrode-based extracellular electrophysiology. Nanoscale needle electrodes can provide high-fidelity electrophysiological interfaces to cardiomyocytes and mammalian neurons, with clear cell-to-electrode registry.
Three-dimensional nanoelectrode array (3D-NEA) for in vivo interrogation of neuronal networks. (a) Scanning electron microscope (SEM) image of the nine silicon nanoneedles that constitute the active region of a 3D-NEA. Dimensions of the nanoneedle electrodes are designed to facilitate single-cell intracellular electrical coupling. False colors show metal-coated tips (gray) and insulating silicon oxide (blue). (Copyright 2012 Nature Publishing Group). (b) Scanning electron micrograph of a rat cortical cell (3 days in vitro, false colored yellow) on top of an electrode pad (false colored blue) (Copyright 2012 Nature Publishing Group). (c) Stimulation and recording of rat cortical neurons. Upper traces show that action potentials (blue: measured by a patch pipet) could be reliably stimulated by voltage pulses applied to the nanoelectrodes (magenta). Similarly, lower traces show that the nanoelectrodes can record action potentials (magenta) stimulated by a patch pipet (blue) (Copyright 2012 Nature Publishing Group). (d) Scanning electron micrograph of a representative 3D brain-interfacing device consisting of 24 probes, each containing arrays of active sites distributed along their length. Inset optical image of the 3D probe array (Copyright 2012 Optical Society of America).
Flexible and active electronics offer another potential option for interfaces to neural circuits and the brain. Significant progress has been made in the areas of ultrathin, flexible, light, biocompatible circuits.
An additional challenge is electrode longevity, which is critical for ensuring the success of brain machine interfaces and long-term studies linking brain activity to behavior. An important milestone in addressing electrode longevity challenges could be a minimally invasive wireless nanoscale probe than can attach itself to a single neuron and report its firing activity for greater than one year.
Nanoparticle labeling and reporting – Over the past few decades, the development of more reproducible and accurate tools for monitoring and controlling chemical reactions has enabled the synthesis of an enormous variety of nanoparticles, nanomaterials, and nanostructures, with controlled composition, organization, shape, and functionalization.
Examples include the evolution of fullerenes, carbon nanotubes, and graphene, materials systems in which desirable electrical and mechanical attributes can be obtained by careful vapor deposition of carbon with accurate control over geometry and bonding.
The authors write that they can also envision nanodevices with active optoelectronic properties, so that they become self-powered neural signal transmitters, perhaps tapping into the brain's metabolic pathways for operating power.
New imaging tools – Optical interrogation of populations of neurons in intact animals critically depends on two things: the ability to deliver light efficiently to the brain and the ability to get light out of the brain. These problems are difficult in the single-cell context and become more challenging when parallel simultaneous measurements are required. New techniques offer improvements in the input of light to the system, as well as the detectors measuring light coming out of the sample.
Optogenetics – Brain activity mapping is tightly linked to optogenetics – the use of light to control well-defined events within targeted elements of intact biological systems. Optogenetic tools are themselves nanoscale devices that can be engineered for new classes of brain activity mapping function, building on molecular structure-function relationships.
Biological hybrids and synthetic biology – Synthetic biology can potentially provide hybrid system interfaces with inorganic fabricated components, including building or bridging 3D optical fiber arrays to provide effectively high optical surface area and multiplexing;for example, thin natural light wave guides in glass sponges.
Theory, modeling, and computation – The Brain Activity Map project may bring us closer to answering ultimate questions about how we think and make decisions, which involve the coordinated activity in large numbers of neurons widely distributed throughout the human brain. Understanding the principles of neural computation will also lead to new devices based on these principles.
The authors conclude their article by pointing out that there are tremendous opportunities for nanoscience and nanotechnology to contribute to neuroscience. They hope that the Brain Activity Map project will bring the past decade's national and international investments in science, technology, and people in nanoscience and nanotechnology to bear on important and challenging problems in brain science.
Michael Berger By – Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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