Regulation of cortical acetylcholine release in the rat as studied by in vivo microdialysis.
Date
2000
Authors
Materi, Leticia Michelle.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
Description
Cortical acetylcholine (ACh) has been implicated in diverse cognitive processes such as learning, memory, and attention. The release of ACh in the cortex is greatest during periods of high-frequency, low-voltage electroencephalographic (EEG) activity which occurs naturally during wakefulness and rapid-eye-movement sleep. Anatomical studies have demonstrated that cortical ACh in the rat is primarily released from the axon terminals of cortically projecting cholinergic neurons located in the nucleus basalis magnocellularis of the basal forebrain. Thus, factors that modulate the activity of the basal forebrain cholinergic neurons or act presynaptically at intracortical cholinergic terminals may alter cortical ACh release and influence cortical EEG arousal.
One factor that may act to regulate cortical ACh efflux and promote sleep is the purine nucleoside adenosine. The effects of intracortical administration of adenosine and selective adenosine receptor agonists and antagonists on cortical ACh release evoked by electrical stimulation of the pedunculopontine tegmental nucleus was tested using in vivo microdialysis in urethane anesthetized Wistar rats. The results demonstrated that cortical ACh release was inhibited by activation of intracortical A1 adenosine receptors but unaffected by infusion of an A2A adenosine receptor agonist.
A second factor that may regulate cortical ACh outflow is the excitatory amino acid glutamate. The cortex receives dense glutamatergic input from a number of subcortical structures and there is increasing evidence for extrasynaptic spillover of glutamate. Thus, glutamate may act at cholinergic terminals to regulate the release of ACh in the cortex. Using in vivo microdialysis, the effects of glutamate and selective ionotropic glutamate receptor agonists and antagonists were examined. It was determined that glutamate regulates cortical ACh outflow via an indirect pathway involving GABAergic neurons.
To determine if a similar circuit existed within the basal forebrain to regulate cortical ACh release and EEG activity, selective ionotropic glutamate receptor agonists were applied to the basal forebrain of urethane anesthetized rats. Activation of these receptors elicited a significant increase in cortical ACh outflow but had only minor effects on cortical EEG activity. Specifically, ionotropic glutamate receptor agonists evoked modest increases in the relative power of high-frequency EEG activity with no change to low-frequency activity.
Together, these data suggest that changes in cortical ACh outflow may be regulated at the level of the axon terminal by adenosine and, indirectly, glutamate. Activation of basal forebrain ionotropic glutamate receptors also influences cortical ACh release as well as EEG activity. Such regulation of cortical ACh release and EEG arousal may contribute to behavioural state regulation, synaptic plasticity, and attentional processes.
Thesis (Ph.D.)--Dalhousie University (Canada), 2000.
One factor that may act to regulate cortical ACh efflux and promote sleep is the purine nucleoside adenosine. The effects of intracortical administration of adenosine and selective adenosine receptor agonists and antagonists on cortical ACh release evoked by electrical stimulation of the pedunculopontine tegmental nucleus was tested using in vivo microdialysis in urethane anesthetized Wistar rats. The results demonstrated that cortical ACh release was inhibited by activation of intracortical A1 adenosine receptors but unaffected by infusion of an A2A adenosine receptor agonist.
A second factor that may regulate cortical ACh outflow is the excitatory amino acid glutamate. The cortex receives dense glutamatergic input from a number of subcortical structures and there is increasing evidence for extrasynaptic spillover of glutamate. Thus, glutamate may act at cholinergic terminals to regulate the release of ACh in the cortex. Using in vivo microdialysis, the effects of glutamate and selective ionotropic glutamate receptor agonists and antagonists were examined. It was determined that glutamate regulates cortical ACh outflow via an indirect pathway involving GABAergic neurons.
To determine if a similar circuit existed within the basal forebrain to regulate cortical ACh release and EEG activity, selective ionotropic glutamate receptor agonists were applied to the basal forebrain of urethane anesthetized rats. Activation of these receptors elicited a significant increase in cortical ACh outflow but had only minor effects on cortical EEG activity. Specifically, ionotropic glutamate receptor agonists evoked modest increases in the relative power of high-frequency EEG activity with no change to low-frequency activity.
Together, these data suggest that changes in cortical ACh outflow may be regulated at the level of the axon terminal by adenosine and, indirectly, glutamate. Activation of basal forebrain ionotropic glutamate receptors also influences cortical ACh release as well as EEG activity. Such regulation of cortical ACh release and EEG arousal may contribute to behavioural state regulation, synaptic plasticity, and attentional processes.
Thesis (Ph.D.)--Dalhousie University (Canada), 2000.
Keywords
Biology, Neuroscience.