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Gene expression in the adult brain

Detailed genomic comparison among sensory receptors performed by leading European scientists produced a detailed map of gene expression during signalling cascades. Association of the molecular profile with activity will help unravel how neuronal cells function.

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Neuronal activity is governed by a complex interplay of signals among different cell types which potentially changes during development. In order to delineate the neural network, we need to understand how large neuronal assemblies are regulated and potential differences and similarities in gene expression among them. The aim of the EU-funded ‘Functional genomics of the adult and developing brain’ (NFG) project was to identify and characterise the functional activity of neuronal cells and networks, and to understand how they are orchestrated at a cellular and molecular level in patterns of gene expression. The project focused on the visual sensory and cortex receptors (hippocampus and neocortex). Using laser capture microdissection, project scientists were able to isolate photoreceptors and cultured retina cells, and analyse their molecular profile using gene expression microarrays. In all the cells analysed, NFG observed a consistent up-regulation of three genes known to be involved in transduction of light (Arrestin (SAG), Guanylate Cyclase Activator 1a (Guca1a) and Guanylate Cyclase Activator 1b (Guca1b)). Up-regulation of these genes was considered to mediate a component of light adaptation occurring after hours of light exposure. Functional tests in animals revealed that prolonged illumination with a steady light induced a partial recovery of the dark current after about two hours. This was associated with gene expression changes that altered the signalling cascade of phototransduction and light adaptation. Additionally, NFG partners characterised different classes of cortical neurons in terms of their electrophysiological phenotypes and cortical activity. In particular, they found that the Pax6 gene was involved in neocortical stem cell maintenance and priming of neuronal gene expression. Collectively, the NFG project obtained a vast array of gene expression data in single neuronal cell groups providing basic knowledge on how a specific molecular profile is translated into neuronal activity. Results are promising for future application in genomics technology in the field of neuroscience.

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