Nanotools for Neuroscience and Brain Activity Mapping

Abstract

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we 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. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function.

State-of-the-art MEMS and microsystem tools for brain research

“…72,73). Additional investment in brain mapping technology is ongoing and justified because even at this rate of doubling we are still far from achieving recording densities capable of whole-brain mapping 6,74 . Although new optical imaging and recording modalities will certainly accelerate this rate of discovery, electrical recording methods still provide the greatest temporal resolution and frequency range.…”

“…The need for technologies to enable cell typing in brain research was highlighted as the number one priority by the U.S. BRAIN Initiative 84 , and combining recording techniques with genetically targeted methods such as optogenetics and pharmacogenetics 85 is expected to make cell typing more reliable 6 . MEMS-based devices can certainly provide the resolution if this expectation proves to be the enabling requirement for new software tools, but device reliability and micro-sized packaging solutions are significant constraints that must be part of the solution.…”

“…Understanding what makes any one neuron fire, or not fire, is a central question in neuroscience, and thus, the ideal sensing tool must span from the single neuron to its complex network of connections if we are to understand how a particular 'cell type' assimilates information 3,4 . In doing so, neuroscientists will identify new circuit 'elements' or neuronal cell types that may someday provide the world with a general theory of brain activity 5,6 , similar to how the periodic table arose from the study of repeating physical properties. Microelectromechanical systems (MEMS) and microsystems have enabled the study of neurons from the single unit to the scale of large populations, and all indications are that these technologies will continue to be an important tool-making platform for the neuroscience community.…”

Hybrid intracerebral probe with integrated bare LED chips for optogenetic studies

“…for electrocorticography (ECoG), have been applied. For the fabrication of neural systems with high-density electrodes, precision machining is increasingly being replaced by microelectromechanical systems (MEMS) technologies (Alivisatos et al 2013). In general, these MEMS-based devices rely on polymers (Stieglitz et al 2005) or silicon Wise et al 2008) as substrate materials, with the latter enabling the co-integration of electrodes with complementary metal-oxide semiconductor (CMOS) integrated circuits performing data preprocessing and multiplexing tasks.…”

Direct interfacing of neurons to highly integrated microsystems

“…To understand how functions and characteristics of neuronal networks arise from the concerted interactions of the involved neurons, it is necessary to have methods that allow for interacting with neuronal functional subunits and ensembles -somas, axons, dendrites, single neurons, as well as entire networks -at high spatiotemporal resolution and in real time [1][2][3][4]. Electrical recordings are among the oldest techniques [3][4][5][6][7].…”