ASSOCIATION OF M1 AND M2 MUSCARINIC RECEPTOR PROTEINS WITH ASYMMETRICSYNAPSES IN THE PRIMATE CEREBRAL-CORTEX - MORPHOLOGICAL EVIDENCE FOR CHOLINERGIC MODULATION OF EXCITATORY NEUROTRANSMISSION

Muscarinic m1 receptors traditionally are considered to be postsynapti c to cholinergic fibers, while m2 receptors are largely presynaptic re ceptors associated with axons. We have examined the distribution of th ese receptor proteins in the monkey cerebral cortex and obtained resul ts that are at odds with this expectation. Using immunohistochemistry with specific antibodies to recombinant m1 and m2 muscarinic receptor proteins, we have demonstrated that both m1 and m2 receptors are promi nently associated with non-cholinergic asymmetric synapses as well as with the symmetric synapses that characterize the cholinergic pathways in the neocortex. At asymmetric synapses, both m1 and m2 receptor imm unoreactivity is observed postsynaptically within spines and dendrites ; the m2 receptor is also found in presynaptic axon terminals which, i n the visual cortex, resemble the parvicellular geniculocortical pathw ay. In addition, m2 labeling was also found in a subset of nonpyramida l neurons. These findings establish that the m2 receptor is located po stsynaptically as well as presynaptically. The association of m1 and m 2 receptors with asymmetric synapses in central pathways, which use ex citatory amino acids as neurotransmitters, provides a morphological ba sis for cholinergic modulation of excitatory neurotransmission.