? ? Many forms of drug addiction lead to longstanding behavioral sensitization and to changes in neural circuits that persist well after administration of the addictive substance is terminated. Neuronal changes can involve drug-induced alterations in patterns of gene expression, increased levels of particular proteins, or morphological changes in specific neuron types. These changes likely contribute to the enduring behavioral effects of drug addiction. Understanding of such long-lasting cellular changes is important for medical efforts towards counteracting their contributions to addiction and to cognitive deficits. Unfortunately, current studies are severely hampered by the dearth of methods that can track long-term progression of cellular properties in live animals. This proposal explores an exciting new in vivo imaging technology that will enable longitudinal studies of how abused substances affect individual neurons and neuronal dendrites. The proposed research will rely on newly developed high-resolution fluorescence endoscopes that are 350-1000 um in diameter and that enable in vivo imaging of neurons and dendrites with micron-scale resolution. The first specific aim seeks to establish the ability to monitor chronically individual neurons deep in the mammalian brain over days to months. This would be powerful for studying cellular consequences of drug abuse, because specific fluorescence probes can reveal changes in neuronal morphology, gene expression, or protein distribution.
The second aim seeks to demonstrate the broad utility of this methodology by using chronic endoscopic imaging to visualize long-term structural effects of fetal ethanol exposure on mouse CA1 hippocampal pyramidal cell dendrites. ? ?
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