AbstractCellular activities within the brain display regional specificity and a neuronal and glia interdependence. Components characterizing the regional specificity of neurons have been identified. However, characterization of the astrocyte remains in question. To identify region specific features of astrocytes, we have characterized the molecular phenotype of cells derived from regions with different levels of neuronal excitability, the cortex and striatum. Astrocytes were identified in cryostat sections of adult rat brain by rapid immunostaining for glial fibrillary acidic protein (GFAP), and individual cells were collected from each region by using laser microdissection (LMD). Total RNA was isolated and subjected to DNA microarray analysis. At least eight genes showed a differential expression level. Among them, aquaporin 4 (AQP4), a water channel protein, was expressed at higher levels within the cortex compared with the striatum, as confirmed by immunohistochemistry. Primary cultured astrocytes isolated from rat cortex or striatum also showed a differential expression of AQP4. These data may reflect unique properties of astrocytes across different brain regions. However, they may also reflect the interactive demands of neurons with different activity levels. Further examination of the heterogeneous astrocyte populations within each region will lend additional support to the regional specificity of neuronal functions and neuronal–glial interactions. © 2012 Wiley Periodicals, Inc.