Opposing regulation of dopaminergic activity and exploratory motor behavior by forebrain and brainstem cholinergic circuits
TL;DR: It is shown that mice lacking total forebrain acetylcholine exhibit enhanced frequency-dependent striatal dopamine release and are hyperactive in a novel environment, whereas mice lacking rostral brainstem acetylCholine are hypoactive, which supports a model in which forebrain and brainstem cholinergic systems act in tandem to regulatestriatal dopamine signalling for proper control of motor activity.
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Abstract: Dopamine transmission is critical for exploratory motor behaviour. A key regulator is acetylcholine; forebrain acetylcholine regulates striatal dopamine release, whereas brainstem cholinergic inputs regulate the transition of dopamine neurons from tonic to burst firing modes. How these sources of cholinergic activity combine to control dopamine efflux and exploratory motor behaviour is unclear. Here we show that mice lacking total forebrain acetylcholine exhibit enhanced frequency-dependent striatal dopamine release and are hyperactive in a novel environment, whereas mice lacking rostral brainstem acetylcholine are hypoactive. Exploratory motor behaviour is normalized by the removal of both cholinergic sources. Involvement of dopamine in the exploratory motor phenotypes observed in these mutants is indicated by their altered sensitivity to the dopamine D2 receptor antagonist raclopride. These results support a model in which forebrain and brainstem cholinergic systems act in tandem to regulate striatal dopamine signalling for proper control of motor activity. Dopaminergic circuits are implicated in exploratory motor behaviour and are modulated by acetylcholine. Using transgenic mouse models, Patelet al. find that loss of forebrain acetylcholine results in exaggerated dopamine efflux and hyperactivity, whereas loss of brainstem acetylcholine leads to hypoactivity.
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