Muscarinic acetylcholine receptors in the hippocampus, neocortex and amygdala: A review of immunocytochemical localization in relation to learning and memory

Immunocytochemical mapping studies employing the extensively used monoclona l antimuscarinic acetylcholine: receptor (mAChR) antibody M35 are reviewed; sd. We focus on three neuronal muscarinic cholinoceptive substrates. which are target regions of the cholinergic basal forebrain system intimately inv olved in cognitive functions: the hippocampus: neocortex: and amygdala. Thr distribution and neurochemistry of mAChR-immunoreactive cells as wall as b ehaviorally induced alterations in mAChR-immunoreactivity; (ir) are describ ed in detail. M35(+) neurons are viewed as cells actively engaged in neuron al functions in which the cholinergic system is typically involved. Phosphorylation and subsequent internalization of muscarinic receptors dete rmine the immunocytochemical outcome, and hence M35 as a tool to visualize muscarinic receptors is less suitable for detection of the entire pool of m AChRs in the central nervous system (CNS). Instead, M35 is sensitive to and capable of detecting alterations in the physiological condition of muscari nic receptors. Therefore. M35 is an excellent tool to, localize alterations in cellular cholinoceptivity in the CNS. M35-ir is not only deter mined by acetylcholine (ACh), but by any substance that changes the phosphorylation /internalization state of the mAChR. An important consequence of this propo sition is that other neurotransmitters than ACh (especially; glutamate) can regulate M35-ir and the cholinoceptive state of a neuron. and hence the fu nctional properties of a neuron. One of the primary objectives of this review is to provide a synthesis of o ur data and literature data on mAChR-ir. We propose a hypothesis: for the r ole of muscarinic receptors in learning and memory in terms of modulation b etween learning and recall states of brain areas at the postsynaptic level as studied by way of immunocytochemistry employing the monoclonal antibody M35. (C) 1999 Elsevier Science Ltd. All rights reserved.