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Viral vector and RNAi strategies to determine the role of beta2 containing nicotinic receptors in aversive learning

Final Activity Report Summary - NICOTINIC RECEPTORS (Viral vector and RNAi strategies to determine the role of beta2 containing nicotinic receptors in aversive learning)

Nicotine, the main addictive component in tobacco, acts at nicotinic acetylcholine receptors (nAChRs) present throughout the brain. Understanding the consequences of nAChR activation in the brain and its relationship to both addiction and other psychiatric disorders will be of great societal value. Investigating the underlying neuroscience provides information that will point to new targets for interventions and therapies that will reduce tobacco consumption or treat psychiatric disorders.

This project has served to begin the development and validation of new tools to study nicotinic receptor function in vivo. Five shRNA constructs, tagged with green fluorescent protein (GFP) have been developed in viral vectors that we can use to down-regulate nAChR function in specific areas of mouse brain, the GFP acts as a marker so we can ascertain the site of infection and gene down-regulation in the brain. These constructs utilise a cutting edge technology where RNA molecules targeted to specific DNA sequences are able to interfere with gene expression and thus selectively down-regulate the gene of interest, in this case beta2 subunit containing nicotinic receptors.

Future studies will use these constructs to study the role of nicotinic receptors in passive avoidance behaviour. A fear associated learning paradigm that is sensitive to both nicotine administration and disruption of nicotinic receptors (in beta2 knockout mice).