Single-case experimental designs (SCEDs) are commonly used in behavior analytic research but rarely used in behavioral neuroscience research. The recent development of technologies that allow control of the timing of neurobiological events such as gene expression and neuronal firing enable the fruitful application of SCEDs for the study of brain-behavior relations. There are at least 3 benefits expected from applying SCEDs to study how neurobiological events affect behavior. First, SCEDs entail direct within- and across-subject assessments of reliability, likely increasing the probability of replication across studies and encouraging a search for the causes of replication failure when they occur. Second, SCEDs focus on behavior in individual organisms producing a body of knowledge that applies to individuals rather than population parameters. Finally, SCEDs require fewer animals, decreasing costs and effort and addressing the ethical obligation to reduce the number of animals used for research. Examples are provided using hypothetical data generated based on published research. Collaborations between behavior analysts and behavioral neuroscientists will bring the world within the skin under direct experimental control and broaden our understanding of the determinants of behavior.

Plasma membrane voltage is a fundamentally important property of a living cell; its value is tightly coupled to membrane transport, the dynamics of transmembrane proteins, and to intercellular communication. Accurate measurement of the membrane voltage could elucidate subtle changes in cellular physiology, but existing genetically encoded fluorescent voltage reporters are better at reporting relative changes than absolute numbers. We developed an Archaerhodopsin-based fluorescent voltage sensor whose time-domain response to a stepwise change in illumination encodes the absolute membrane voltage. We validated this sensor in human embryonic kidney cells. Measurements were robust to variation in imaging parameters and in gene expression levels, and reported voltage with an absolute accuracy of 10 mV. With further improvements in membrane trafficking and signal amplitude, time-domain encoding of absolute voltage could be applied to investigate many important and previously intractable bioelectric phenomena.