Molecular dissection of the amygdala and its relevance to autism.

The limbic system, and in particular the amygdala, have been implicated in autism. The amygdala is a complex structure that in rodents consists of at least 12 different nuclei or subnuclei. A comparative analysis of amygdala neuroanatomy in normal vs. autistic brains would be aided by the availability of molecular markers to unambiguously recognize these different amygdala substructures. Here we report on the development of methods to identify genes enriched in the central, lateral and medial nuclei of the rodent amygdala. Our results suggest that laser-capture microdissection of specific amygdala subnuclei, when combined with linear amplification of cRNA probes for oligonucleotide microarray hybridization, can efficiently identify genes whose expression is confined to these substructures. Importantly, many of these genes were missed in previous gene expression-profiling experiments using whole amygdala tissue. The isolation of human orthologs of these subnucleus-specific genes, and/or the application of these methods directly to human tissue, may provide useful markers for characterizing neuropathological correlates of autism, as well as for identifying molecular differences between normal and autistic brains.