Connected by trillions of synapses

Connected by trillions of synapses and gap junctions, neurons and glia in the brain ex- change (bio)chemical, electrical, and me- chanical cues. This symphony of signals originates at the nanoscale, where molecu- lar machinery coordinates chemical reac- tions and conformation changes, e.g., ion channel opening. Combined, these events govern cellular function at the microscale, e.g., action potential firing. Coordination on the microscale then translates into emer- gence of macroscale neural circuits, which drive behavior. Creating tools capable of recording and manipulating this signaling diversity across scales ranging from nano- meters (biomolecules) to centimeters (entire organisms) requires seamless integration of many functional features within neurobiolog- ical probes. Such integration, in turn, relies on a continuous dialog between the biolog- ical and physical scientists and cannot be simply limited to the sequential attach- ment of engineering modules designed to ‘‘service’’ molecular or electrophysiological tools. The physical properties of the neural tissue and its adverse response to the external hardware further impart design con- straints onto synthetic sensors and actua- tors of brain signaling. To deterministically link naturally occurring behaviors to a series of molecular events within the brain, it may be necessary to pivot away from existing engineering infrastructures toward biologi- cally inspired design of materials and de- vices that can transduce signals to and from molecular machines within behaving organisms.