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Cholinergic modulation of the cortical microvascular bed
1Laboratory of Cerebrovascular Research, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada. edith.hamel@mcgill.ca
Progress in Brain Research
|December 4, 2003
Summary
Basal forebrain stimulation dilates cortical microvessels via acetylcholine (ACh) acting on M5 receptors, influencing NO production. Alzheimer's disease impairs this crucial cortical perfusion regulation.
Area of Science:
- Neuroscience
- Vascular Biology
- Cholinergic System
Background:
- Cortical microvessels are modulated by cholinergic input from basal forebrain neurons.
- Muscarinic acetylcholine receptors (mAChRs) subtypes M1-M5 are present in cortical microvessels.
- Acetylcholine (ACh) influences cortical blood flow and microvessel diameter.
Purpose of the Study:
- To investigate the direct effects of basal forebrain cholinergic stimulation on cortical microcirculation.
- To identify the specific mAChR subtypes involved in ACh-mediated microvascular responses.
- To explore the role of intracortical neurons and their projections in mediating these effects.
Main Methods:
- Application of ACh to isolated, pressurized rat cortical microarterioles.
- Assessment of nitric oxide (NO) production and mAChR pharmacology.
- Investigation of GABA interneuron projections and VPAC1 receptor expression.
Main Results:
- ACh application caused vasodilation in cortical microarterioles, dependent on NO production.
- The vasodilation was mediated by a mAChR consistent with the M5 subtype.
- ACh also targets intracortical neurons, including GABA interneurons projecting to microvessels, suggesting a relay mechanism.
Conclusions:
- Basal forebrain ACh directly impacts the cortical microvascular bed, primarily through M5 mAChRs and NO.
- GABA interneurons may act as a functional relay, adapting cortical perfusion to neuronal activity.
- Dysfunction of ACh and NO regulation in Alzheimer's disease suggests impaired cortical perfusion control.