Experience shapes the functional capacity of the brain to suit the unique needs and environment of the individual. How such adaptive change occurs is of great interest as it circumscribes the individual's long-term behavior and capabilities. Despite this importance, the underlying molecular mechanisms are largely unknown. The goal of this proposal is to identify how the global pattern of neural gene expression changes during adaptive plasticity. The neural circuit under study is the barn owl sound localization pathway. Within this pathway, auditory and visual maps of space are aligned and integrated to yield a unified representation of the animal's surround. The co-registration of these maps can be manipulated by fitting owls with horizontally displacing prismatic spectacles (prisms). After several weeks of prism experience, the auditory space maps in the external nucleus of the inferior colliculus (ICX) and optic tectum (OT) adaptively adjust, restoring proper alignment and behavioral performance. This adaptive plasticity involves topographically appropriate axonal sprouting and synaptogenesis. The scope and persistence of structural remodeling strongly suggest that changes in neural gene expression underlie adaptive adjustment. To identify the crucial plasticity molecules, we will analyze genome-wide expression in the ICX and OT using serial analysis of gene expression (SAGE). The first set of experiments focuses on prism adaptation in juvenile owls. Functional phases of adaptive plasticity will be defined by auditory mapping experiments. SAGE analysis will be performed on adapted and non-adapted parts of the auditory map extracted from the same individual. Direct comparison will reveal the known and novel neural genes that are differentially regulated by prism experience. The second set of experiments will identify changes in gene expression associated with the enhanced capacity for plasticity displayed by prism-adapted adult owls. The third set of experiments involves mapping the spatio.-temporal patterns of expression of differentially regulated transcripts to different neuronal cell types using in situ hybridization. We expect that the data obtained by this approach will be broadly applicable to higher mammals including humans. Our long-term objective is to identify novel genes that play crucial roles during normal learning processes, and by extension, whose malfunction may contribute to learning disabilities and neurological disorders that involve a failure in neuroplasticity.
