The aim of the project is to determine how disruption of cholinergic activation of striatal GABAergic interneurons alters striatal signalling and striatum-based behaviour by using a mouse model with deletion of the β2 nicotinic acetylcholine receptor subunit in striatal GABAergic interneurons.
The striatum is the main input nucleus of the basal ganglia, a complex structure controlling motor and executive functions, reward-related processes and learning. The striatum is composed of GABAergic output neurons and two types of interneurons, cholinergic (CINs) and GABAergic. CINs, due to their rich axonal branching and semi-synchronized activity, have a large impact on striatal circuits. CINs can modulate the activity of striatal output neurons and they control the release of glutamate and dopamine through the nicotinic acetylcholine receptors (nAChRs) expressed by striatal projection terminals. While these mechanisms have been extensively studied, little is known about cholinergic activation of striatal GABAergic interneurons expressing α4β2 nAChRs. The aim of the project is to determine how disruption of cholinergic activation of striatal GABAergic interneurons alters striatal signalling and striatum-based behaviour. To do that, we will develop a mouse model with deletion of the β2 nAChR subunit in striatal GABAergic interneurons and characterize this model with a special focus on striatum-based behaviour and biochemical alterations in the striatum.
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