Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.

The Allen Brain Atlas (http://www.brain-map.org) provides a unique online public resource integrating extensive gene expression data, connectivity data and neuroanatomical information with powerful search and viewing tools for the adult and developing brain in mouse, human and non-human primate. Here, we review the resources available at the Allen Brain Atlas, describing each product and data type [such as in situ hybridization (ISH) and supporting histology, microarray, RNA sequencing, reference atlases, projection mapping and magnetic resonance imaging]. In addition, standardized and unique features in the web applications are described that enable users to search and mine the various data sets. Features include both simple and sophisticated methods for gene searches, colorimetric and fluorescent ISH image viewers, graphical displays of ISH, microarray and RNA sequencing data, Brain Explorer software for 3D navigation of anatomy and gene expression, and an interactive reference atlas viewer. In addition, cross data set searches enable users to query multiple Allen Brain Atlas data sets simultaneously. All of the Allen Brain Atlas resources can be accessed through the Allen Brain Atlas data portal.

Cryptochromes regulate the circadian clock in animals and plants. Humans and mice have two cryptochrome (Cry) genes. A previous study showed that mice lacking the Cry2 gene had reduced sensitivity to acute light induction of the circadian gene mPer1 in the suprachiasmatic nucleus (SCN) and had an intrinsic period 1 hr longer than normal. In this study, Cry1 ؊͞؊ and Cry1 ؊͞؊ Cry2 ؊͞؊ mice were generated and their circadian clocks were analyzed at behavioral and molecular levels. Behaviorally, the Cry1 ؊͞؊ mice had a circadian period 1 hr shorter than wild type and the Cry1 ؊͞؊ Cry2 ؊͞؊ mice were arrhythmic in constant darkness (DD). Biochemically, acute light induction of mPer1 mRNA in the SCN was blunted in Cry1 ؊͞؊ and abolished in Cry1 ؊͞؊ Cry2 ؊͞؊ mice. In contrast, the acute light induction of mPer2 in the SCN was intact in Cry1 ؊͞؊ and Cry1 ؊͞؊ Cry2 ؊͞؊ animals. Importantly, in double mutants, mPer1 expression was constitutively elevated and no rhythmicity was detected in either 12-hr light͞12-hr dark or DD, whereas mPer2 expression appeared rhythmic in 12-hr light͞12-hr dark, but nonrhythmic in DD with intermediate levels. These results demonstrate that Cry1 and Cry2 are required for the normal expression of circadian behavioral rhythms, as well as circadian rhythms of mPer1 and mPer2 in the SCN. The differential regulation of mPer1 and mPer2 by light in Cry double mutants reveals a surprising complexity in the role of cryptochromes in mammals.gene targeting ͉ photoreceptor ͉ suprachiasmatic nucleus C ircadian rhythms are oscillations with daily periodicities in physiological and behavioral functions of organisms (1-3). The rhythms are generated by a cell-autonomous circadian oscillator (4) that is synchronized with the environment by light. Recently, it was proposed that, in mammals, the nonopsin pigments, cryptochrome blue-light photoreceptors (5, 6), may be the photoactive pigments that synchronized the molecular oscillator and, ultimately, the organismic circadian rhythm with the daily light-dark cycle (7,8). In humans and mice there are two genes encoding the apoproteins of the cryptochromes: CRY1 and CRY2 in humans and Cry1 and Cry2 in mice (6,8,9). Both genes are expressed throughout the body (8-11). Of particular interest, both Cry1 and Cry2 are expressed at high levels in the ganglion cells and the inner nuclear layer of the retina, which are known to be important for circadian photoreception, and Cry1 is expressed with a robust circadian rhythm in the suprachiasmatic nucleus (SCN) (8).In a previous study (12), we found that mice lacking a functional Cry2 gene (i) had reduced sensitivity to acute light induction of the clock gene mPer1 (mouse period gene 1) in the SCN, (ii) had an intrinsic circadian period about 1 hr longer than normal, and (iii) exhibited high amplitude phase shifts in response to light pulses administered at circadian time (CT) 17. These data, and related findings in cryptochrome mutants of Drosophila melanogaster (13) and Arabidopsis thaliana (14), supported the notion that cr...