Microarrays and the microscope: balancing throughput with resolution

Abstract

The cellular complexity of the brain is a major issue in the planning, execution and interpretation of microarray studies. Recent technical advances allow for high-throughput study of specific cell populations and circuits. Here we review representative examples of currently available methods that allow high resolution and specificity in brain microarray studies, while maintaining the goal of comprehensive, high-throughput analysis.

Figure 1. Schematic illustrating the major methods currently available to address regional and cell specificity in human brain and experimental models

In human brain, neuroanatomical methods can be used to guide dissection and laser-guided microdissection. Voxelation approaches allow visualization of 3D gene expression maps. In experimental models, in addition to image-based methods, cell specificity can be achieved with labelling methods, based on both neuroanatomical and genetic markers (e.g. http://www.ncbi.nlm.nih.gov/projects/gensat/). Such intrinsic labels can be used to guide dissection or FACS-based approaches. Most of these methods require an amplification step due to low RNA amounts, prior to gene expression profiling using microarrays. Many robust methods for such amplification are now widely available, making this a worthwhile approach.