Chapter 34: Central cholinergic mechanisms and function

Abstract

Central actions of ACh, liberated at cholinergic synapses, are mediated by both muscarinic and nicotinic receptors. So far, much the most prominent have been muscarinic actions. Activation of muscarinic receptors can result in either excitation (most often, especially in cortical regions) or inhibition. These excitatory or inhibitory effects are mediated by a variety of mechanisms, as described in this chapter. In contrast to the (nicotinic) paradigmal fast excitatory transmitter actions of ACh at the neuromuscular junction and sympathetic ganglia and of glutamate at central synapses, both of which are produced by the opening of membrane conductances that generate an inward current, muscarinic excitations are produced by the suppression of on-going outward currents. Although indirect and slower, this can be a powerful effect, because most central neurons are subject to the continual stabilizing action of endogenous, more-or-less voltage-dependent K-currents, as well as synaptically activated C1 channels. Both of these muscarinic actions are discussed. Two other excitatory effects listed in the chapter, enhanced NMDA-receptor mediated synaptic responses and increased ephaptic (direct electrical) interactions between neighboring neurons, are also discussed in the final section of this chapter.