7 Muscarinic receptors M1 – M5 metabotropicexcitatory: slow long lasting depolarisationdue to closure of the K+ channelM1, M3, M5inhibitory: slow long lasting hyperpolarisationdue to opening of the K+ channelM2, M4ACH auto-receptorsN receptor: positive feed-back, fast onsetfast desensitizationM receptor negative feed back, slow onsetslow desensitization
11 Specific toxins for ACH neurons AF 64: CAT inactivationinhibits the transporter (by alcylation)192 IgG-Saporin: Immunotoxinantibody against p75NGF(=low affinity NGF receptor whichis localized upon ACH neurons)
12 Anatomy of the ACH System Periphery: Motor end plateVegetaive NS:Sympathicus preganglionic: ACH - N receptorpostganglionic: NoradrenalinParasympath. preganglionic: ACH – N receptorpostanglionic: ACH – M receptorBrain: –10 % are ACH ergicNucleus basalis whole cortexSeptum hippocampusPPTg VTA (mesencephalon)
13 Figure: Central cholinergic pathways Figure: Central cholinergic pathways. The six major cholinergic projection groups (sectors) are depicted (Ch1-Ch6). Therein, projections from Ch1/Ch2 and Ch4 to hippocampal, limbic and neocortical areas are implicated in learning and memory processes.
14 Physiology/Pathophysiology of ACH Septum – hippocampus: learning, M-receptor mediatedhippocampal theta rhythmtransiently during orienting behaviourM-receptor mediatedNBM - cortex learning N+M receptor mediatedattentionPPTg – VTA brain reward