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Basal forebrain cholinergic neurons: regulation by dopamine and responses to arousing stimuli Day, Jamie Catherine


The regulation of forebrain cholinergic systems, specifically those neurons in the cholinergic basal nuclear complex (CBC) which project to the hippocampus and cortex are of great interest, given the involvement of acetyicholine (ACh) in cognitive function. To assess the activity of CBC neurons, in vivo microdialysis has been used in the present experiments to measure ACh release in the hippocampus and cortex of freely moving rats. Dialysate concentrations of ACh in the hippocampus and cortex (and striatum) of freely moving rats were found to correlate positively and significantly with locomotor activity, a behavioural measure of arousal. Two arousing stimuli, injection of vehicle and onset of the rats’ dark phase, increased locomotor activity and ACh release in all three brain regions, as did injection of the muscarinic antagonist scopolamine. These data suggest that forebrain cholinergic neurons are responsive to arousing stimuli and that ACh release in the crtex, hippocampus and striatum generally correlates with arousal. The dopaminergic regulation of CBC neurons was examined by determining the extent to which dopamine (DA) receptor agonists and antagonists affect cortical and hippocampal ACh release. The indirect DA agonist d-amphetamine (AMPH) and the DA receptor agonist apomorphine increased ACh release in both the cortex and hippocampus as did the selective D1 receptor agonist CY 208-243. D2 receptor agonists (quinpirole and/or PHNO) had no effect on ACh release in the cortex and produced slight decreases in the hippocampus. In addition, the AMPH-induced increases in ACh release in both regions were attenuated more by the D1 receptor antagonist SCH 23390 than by the D2 antagonists haloperidol and/or raclopride, as was the apomorphine induced release of ACh in the cortex. That DA mediates AMPH-induced increases in cortical ACh release was supported by the finding that prior selective lesions of ascending dopaminergic but not noradrenergic systems attenuated this effect of AMPH. These results suggest that CBC neurons are regulated in an excitatory manner by DA acting primarily at D1 receptors. The extent to which ACh release in the cortex and hippocampus is related to the performance of a learned behavioural task was assessed in rats trained to anticipate and consume a palatable liquid diet. Hippocampal ACh release increased during the anticipatory and consummatory periods of the task, but the increase observed in rats trained with the liquid diet was not higher than the increases seen in rats trained with water or in naive rats. In contrast, cortical ACh release increased to a greater extent in rewarded rats than it did in the two control groups. This suggests that cholinergic activity in both the cortex and hippocampus is increased by a reward-independent aspect of the task, such as arousal or attention, while an additional reward-dependent component is seen with respect to cortical ACh release.

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