Pharmacological but not physiological modulation of cortical acetylcholine release by cholinergic mechanisms in the nucleus basalis magnocellularis.
The role of muscarinic transmission in the activation of cholinergic neurons ascending to the neocortex from the nucleus basalis magnocellularis (NBM) was investigated. The release of acetylcholine (ACh) from the neocortex of urethane-anesthetized rats was measured using microdialysis, and a second microdialysis probe was inserted into the NBM to apply drugs to the NBM and to measure ACh release from this area. Cholinergic neurons in the NBM were activated synaptically by stimulating the pedunculopontine tegmentum (PPT). Systemically administered scopolamine greatly increased the PPT stimulation evoked cortical release of ACh when the cortical probe was perfused with the cholinesterase inhibitor neostigmine. PPT stimulation evoked release was also high when the cortical probe was perfused with atropine plus neostigmine, but it was not increased any further by systemic scopolamine or by scopolamine perfused through the NBM probe. When neostigmine was perfused through the NBM probe, PPT stimulation evoked cortical ACh release was halved, but the release was restored when the NBM solution also contained scopolamine. The resting release of ACh within the NBM was increased by local neostigmine, but evoked release in the NBM was large only in the presence of local scopolamine. Both of these increases were blocked by perfusion of the NBM with tetrodotoxin. These results suggest that muscarinic transmission within the NBM does not control the activation of cholinergic neurons under physiological conditions, when the diffusion of ACh is limited by its hydrolysis. However, when ACh is allowed to diffuse to a wider area, it may inhibit the release of an excitatory transmitter, probably glutamate, via presynaptic muscarinic receptors.
Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada.
J C
JC
Szerb
K
K
Clow
D D
DD
Rasmusson
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D018678:Cholinergic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D017551:Microdialysis / Q000379:methods; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology; D013377:Substantia Innominata / Q000187:drug effects / Q000378:metabolism*
D018678:Cholinergic Agents; D012601:Scopolamine; D000109:Acetylcholine