Nicotinic acetylcholine receptors

Nicotinic acetylcholine receptors (AChRs) are multimeric proteins made of 5 subunits. These subunits can combine in multiple ways to form a wide range of so-called nAChR subtypes. These receptor subtypes are present in different neuronal systems and play different roles in the brain. As a consequence, they contribute to different physiological functions and may be differentially altered in pathological conditions.

In this project, we will determine the subunit composition and functional role of nAChR subtypes in different brain regions, by combining a number of methodological approaches that can characterize these types of receptors in the living animal (in vivo techniques, such as intracerebral microdilaysis and behavioral analysis) or in neuronal tissues extracted from the brain (ex vivo techniques, such as receptor binding and neuromorphological techniques).

Our analysis will be focused on neural systems that are main in vivo targets of nicotine, such as the mesocorticolimbic dopamine system, that mediates its addictive properties. In fact, nicotine is a main component of tobacco smoke and is thought to be responsible for the development of dependence to tobacco. The investigation will apply these techniques to animal models of nicotine addiction taking advantage of a large number of unique experimental tools developed by the partners of the consortium, such as transgenic animals, or animals infected with viruses, that are devoid, or hyperexpress, specific nAChR subtypes, and molecular tools specific for nAChR subtypes.