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Basal forebrain cholinergic neurons: regulation by dopamine and responses to arousing stimuli Day, Jamie Catherine
Abstract
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.
Item Metadata
Title |
Basal forebrain cholinergic neurons: regulation by dopamine and responses to arousing stimuli
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1994
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Description |
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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Extent |
2495489 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-04-14
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0088020
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1994-11
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.