Single-cell analysis of gene expression in the nervous system. Measurements at the edge of chaos.
The characteristic functions of tissues and organs result from the integrated activity of individual cells. Nowhere is this more evident than in the nervous system, where the activities of single neurons communicating via electrical and chemical signals mediate complex functions, such as learning and memory. The past decade has seen an explosion in the identification of genes encoding proteins, such as voltage-gated channels and neurotransmitter receptors, responsible for neuronal excitability. These studies have highlighted the fact that even within a neuroanatomically defined region, the coexistence of multiple cell types makes it difficult, if not impossible, to correlate patterns of gene expression with function. The recent development of techniques sensitive enough to study gene expression at the single-cell level promises to break this bottleneck to our further understanding. Using examples taken from our own laboratories and the work of others, we review these techniques, their application, and discuss some of the difficulties associated with the interpretation of the data.