Chapter 8: Neurotransmitter Systems I: Acetylcholine & the Amino Acids

Anne B. Theibert

OBJECTIVES

Objectives

After studying this chapter, the student should be able to:

Diagram the synthesis, packaging, and degradation of acetylcholine (ACh).
Distinguish the 2 types of ACh receptors and describe their mechanisms of action.
Identify the main types and location of cholinergic neurons in the central and peripheral nervous systems.
Illustrate the mechanisms of glutamate packaging, interconversion with glutamine, and glutamate uptake.
Describe the different types of ionotropic and metabotropic glutamate receptors and their modes of regulation and function.
Identify the general types and locations of glutamatergic neurons.
Diagram the synthesis, packaging, and uptake of γ-aminobutyric acid (GABA) and glycine.
Identify the locations where GABAergic and glycinergic neurons function.
Distinguish the types of ionotropic and metabotropic GABA receptors and the glycine receptor.
Describe the mechanisms of GABA and glycine-mediated synaptic inhibition.
Define glutamate excitotoxicity and the excitation/inhibition (E/I) ratio, and identify the importance of each.

NEUROTRANSMITTERS IN NEURONAL TRANSMISSION

The previous chapter provided an overview of synapses and general mechanisms of neurotransmitter (NT) packaging, release, and receptors. In this chapter, the specific NT systems involving acetylcholine (ACh) and the amino acids glutamate (Glu), γ-aminobutyric acid (GABA), and glycine (Gly) are described. For these NT systems, neurotransmission between the presynaptic neuron that releases the NT and its target can be complex (Figure 8–1). Synaptic/wiring transmission involves activation of NT receptors in the postsynaptic and presynaptic regions. Volume transmission involves receptors in the perisynaptic or extrasynaptic regions and/or adjacent neurons. Fast synaptic transmission involves ionotropic NT receptors, which produce rapid changes in the postsynaptic membrane potential. Slow synaptic transmission involves metabotropic G-protein–coupled receptors (GPCRs), which produce slow changes in the membrane potential. GPCRs also act as neuromodulators to alter the cellular or synaptic properties of neurons so that synaptic transmission between them is modified. Many target neurons express both ionotropic and metabotropic receptors for the same NT, and the NT receptors can be localized postsynaptically, presynaptically, perisynaptically, and/or extrasynaptically. Consequently, using NTs, the presynaptic neurons can excite, inhibit, and/or modulate their postsynaptic targets, with short-term effects on membrane potential and/or longer lasting effects on neuronal excitability, synaptic transmission, metabolism, morphology, and gene expression.

FIGURE 8–1

Types of synaptic transmission at chemical synapses. A. In fast, direct transmission, a presynaptic action potential activates voltage-gated Ca²⁺ channels, influx of Ca²⁺ (red spheres) and release of neurotransmitter (purple spheres) into the synaptic cleft. Neurotransmitters bind to ionotropic receptors leading to changes in the postsynaptic membrane potential. B. In slow, indirect transmission, released neurotransmitters (blue spheres) can diffuse inside and outside the synaptic cleft and activate receptors located at different sites. Left, activation of presynaptic metabotropic receptors leads to regulation of neurotransmitter release. Middle, activation of postsynaptic metabotropic receptors leads to modulation of ionotropic receptors. Right, activation of metabotropic receptors in the cell body or nearby synapses or neurons, can lead to effects on multiple targets including ion channels and other activities.