Engineering approaches to illuminating brain structure and dynamics

Abstract

Historical milestones in neuroscience have come in diverse forms, ranging from the resolution of specific biological mysteries via creative experimentation to broad technological advances allowing neuroscientists to ask new kinds of questions. The continuous development of tools is driven with a special necessity by the complexity, fragility, and inaccessibility of intact nervous systems, such that inventive technique development and application drawing upon engineering and the applied sciences has long been essential to neuroscience. Here we highlight recent technological directions in neuroscience spurred by progress in optical, electrical, mechanical, chemical, and biological engineering. These research areas are poised for rapid growth and will likely be central to the practice of neuroscience well into the future.

Figure 1. Optics and Protein Engineering Converge for Ca²⁺ Imaging in >1,200 CA1 Pyramidal Cells in Freely Moving Mice

(A) An integrated microscope is equipped with a microendoscope to image CA1 neurons expressing the engineered Ca²⁺ indicator GCaMP3 under control of the Camk2a promoter. The base plate and microendoscope are fixed to the cranium for repeated access to the same field of view. Republished from Ziv et al., 2013. (B) Shown are 1,202 CA1 pyramidal cells (red somata) identified by Ca²⁺ imaging in a freely moving mouse atop a mean fluorescence image (green) of CA1. Vessels appear as dark shadows. Image courtesy of Yaniv Ziv and Lacey Kitch, Stanford University. (C) Example traces of [Ca²⁺]_i dynamics from 15 cells. Scale bars denote 5% ΔF/F (vertical) and 10 s (horizontal).

Figure 2. Materials Science and Optoelectronics Converge for Neural Interface Research

Left: exploded-view layout of injectable semiconductor device for integrated stimulation/sensing/actuation, highlighting distinct layers for electrophysiological measurement (1), optical measurement (2), optical stimulation (3, micro-ILED array), and temperature sensing (4), all bonded to a releasable base for injection with a microneedle. Top right: injection and release of the microneedle. After insertion (left), artificial cerebrospinal fluid dissolves an external silk-based adhesive (middle) and the microneedle can be removed (right), leaving the active device in the brain. Bottom right: SEM of an injectable micro-LED array, 8.5 μm thick; flexible and rigid forms shown. Adapted with permission from Kim et al., 2013.

Figure 3. Chemical Engineering, Bioengineering, and Photonics Give Rise to Circuit-Probing Hardware and Wetware

Top: construction of a hydrogel from within tissue (CLARITY) creates a transparent mammalian brain for intact-system anatomical analysis; adapted from Chung et al., 2013. Bottom left: 2.3Å crystal structure of the channel-rhodopsin optogenetic control tool enables directed protein engineering for enhanced interventional functionality; adapted from Kato et al., 2012. Bottom right: optogenetic neural interfaces deliver light from laser diodes or advanced LEDs; flexible fiberoptic control in freely moving mouse shown. Photo credit Inbal Goshen and Karl Deisseroth.