Muscarinic receptor M-2 in cat visual cortex: Laminar distribution, relationship to gamma-aminobutyric acidergic neurons, and effect of cingulate lesions

Acetylcholine can have diverse effects on visual cortical neurons as a resu lt of variations in postsynaptic receptor subtypes as well as the types of neurons and subcellular sites targeted. This study examines the cellular ba sis for cholinergic activation in visual cortex via M-2 type muscarinic rec eptors in gamma -aminobutyric acid (GABA)-ergic and non-GABAergic cells, us ing immunocytochemical techniques. At light microscopic resolution, M-2 imm unoreactivity (-ir) was seen in all layers except area and sublayer specifi c bands in layer 4. Subcellularly, M-2-ir occurred in both dendrites and te rminals that form symmetric and asymmetric junctions. Layers 5 and 6 were c haracterized by axosomatic contacts that displayed labeling in the presynap tic component, and layer 6 displayed perikaryal postsynaptic staining, sugg esting that corticofugal output neurons may be modulated particularly stron gly via M-2. Infragranular layers differed from the supragranular layers in that more labeled profiles were axonal than dendritic, indicating a domina nt presynaptic effect by acetylcholine via M-2 there. Unilateral cingulate cortex cuts caused reduction of cholinergic and noradrenergic fibers in the lesioned hemisphere at light microscopic resolution; at electron microscop ic resolution, the synapse density and axonal M-2 labeling were reduced, su ggesting that M-2 was localized presynaptically on extrathalamic modulatory inputs. Dual labeling with GABA in visual cortex layer 5 showed that half of M-2-labeled dendrites originated from GABAergic neurons. Given that only one-fifth of all cortical dendritic profiles are GABAergic, this prevalenc e of dual labeling indicates an enrichment of M-2 within GABAergic dendrite s and, thus, implicates abundant postsynaptic action on GABAergic neurons v ia M-2. In contrast, only one-tenth of M-2-labeled terminals originated fro m GABAergic neurons, suggesting that the presynaptic action of acetylcholin e via M-2 receptors would be more selective for non-GABAergic terminals. J. Comp. Neurol. 441:168-185, 2001. (C) 2001 Wiley-Liss, Inc.