Optogenetic analysis of mammalian neural circuits

The identification, characterization and development of optogenetic probes,
described extensively in the previous chapters, have provided us with a remarkable set of tools for probing brain function. The resulting “optogenetic revolution” has captured the attention of a whole generation of scientists working at different levels of nervous system function. The power of the optogenetic approach is particularly appealing for those working at the levels of neural circuits and neural systems in the mammalian brain. This is because circuits and systems pose special challenges – and offer remarkable opportunities – for experimenters seeking to understand the functional organization of the mammalian brain. Neural circuits and systems are at the interface between the cellular and molecular levels of analysis and higher-level functions such as behavior and cognition; thus, any mechanistic understanding of brain function must embrace the level of the circuit as an essential bridging element. However, not only are mammalian circuits incredibly complex, consisting of diverse cell types with elaborate morphologies linked by intricate webs of synaptic connections; but activity patterns in neural circuits during behavior take place on the millisecond timescale and engage thousands to millions of neurons. It is partly because of this complexity that optogenetics holds such promise, because it offers the possibility of precisely targeted interventions both in space and time. In this chapter we will discuss how optogenetics has helped us to address fundamental questions at each of these levels, and also outline some of the challenges that remain, both for interpreting existing experimental data, and in designing new probes and approaches for maximizing the power of optogenetic intervention.