Novel approaches to monitor and manipulate single neurons in vivo

The complexity of the vertebrate brain poses an enormous challenge to experimental neuroscience. One way of dealing with this complexity has been to investigate different aspects of brain function in widely different preparations, each best suited to address a particular question. Accordingly, cellular questions are typically addressed with intracellular recordings in in vitro preparations such as brain slices or neuronal cultures, whereas network behavior and sensory or motor response properties are analyzed in vivo, often with extracellular recordings. This division of labor has proved to be an experimentally effective strategy. However, although there seems to be no limit to the wealth of data that can be generated in this way, integrating results derived in different preparations comes with its own set of challenges. The enormous difficulties encountered when one attempts to link cellular phenomena such as synaptic plasticity to systems properties such as spatial memory (Martin et al., 2000) have shown us that close collaboration between molecular−cellular and systems neuroscience is required (Tonegawa et al., 2003) and that we need more convergence of experimental techniques to analyze the cellular basis of neural function under more natural conditions. Studying neurons under naturalistic conditions is, however, easier said than done. A return to in vivo preparations will only be successful if we are able to solve the technical problems that led previous researchers to abandon the study of intact brains in the first place. Thus, studying neurons at the cellular level in vertebrate brains is today first and foremost a technological challenge. Here we highlight recent efforts to improve our ability to analyze functions of single neurons in vivo. Given th