, 2013). This general approach may also synergize with the studies of the development and assembly of neural structures beginning

from the other direction, with biology rather than chemistry, as in the stem cell/brain organoid (Lancaster et al., 2013) approach described above. A newly emerged concept at the interface of neuroscience and chemical learn more engineering, CLARITY (Figure 3), involves the chemical construction of new physical forms from within biological systems such as the brain (Chung and Deisseroth, 2013 and Chung et al., 2013). For example, hydrogel infrastructures can be constructed from within intact brains to covalently stabilize native proteins and nucleic acids in preparation for stringent removal

of membrane phospholipids with strong ionic detergents and active electrophoresis of the entire brain. This lipid removal, in turn, allows interrogation of the intact brain with photons (which no longer scatter heavily due to removal of the lipid-aqueous interfaces) and macromolecules (such as antibodies and oligonucleotide probes, which can at that point penetrate the tissue without interference from intact plasma membranes). We expect this kind of approach to find utility in mapping volumetric anatomical features from animal models as well as clinical samples; moreover, many kinds of gels and scaffolds could be constructed in this way with a range of passive and active properties for a broad range of different kinds of structural and functional GS-7340 clinical trial studies of nervous systems. Finally, distinct from gel and scaffold diversity, there also exists

a broad diversity of macromolecular probe type that can be used to interrogate the resulting nanoporous hybrid structures, including functionalized proteins and active enzymes. As exciting as these domains of neuroscience have become, the future may hold even greater opportunities—for example, via combinations of multiple engineering subdisciplines (e.g., computer science with chemical engineering, or optical instrumentation with bioengineering, for applications to increasingly sophisticated questions in increasingly complex nervous systems; Figure 3). CLARITY is already being used in human tissue, and advanced electrical and optical interfaces else have already been designed for human and nonhuman primate applications. Emerging optical methods may bring among the most exciting synergistic possibilities for integrative studies of neural circuit dynamics, connectivity, cytoarchitecture, and molecular composition. Specifically, in vivo optical recordings of neural activity and optogenetic manipulations in cells defined genetically or by anatomical projections can be naturally combined and registered with technologically advanced studies of circuitry, synaptic structure, and other macromolecular information (e.g., using CLARITY).