SYNTHESIS, PACKAGING, RELEASE, AND REMOVAL OF NEUROTRANSMITTERS

Where are neurotransmitters made and how are they packaged?

Small neurotransmitters (like NO and CO ) are synthesized at the presynaptic terminals of a neuron using enzymes manufactured in the cell body. Neurotransmitter precursors are pulled into the cell at the synaptic terminal and used to create neurotransmitter molecules that will be loaded into vesicles before being dumped into the synapse. See diagram below, part B.

In contrast, larger polypeptide neurotransmitters such as acetylcholine and serotonin tend to be synthesized in the cell body of the neuron by the rough endoplasmic reticulum before being packaged into vesicles by the Golgi apparatus. These peptide neurotransmitters may undergo further processing inside the vesicles as well. See diagram below, part C.

So how do the peptide neurotransmitters get from the cell body to the terminal end of the axon?

Fast axonal transport allows vesicles to travel as fast as 400 mm/day (as opposed to ~5 mm/day for the slow axon transport that carries enzymes to the axon terminus). In this fast mode of transport vesicles are moved along long microtubule "tracks" by ATP-driven motor proteins.

What happens to neurotransmitters after they are released into the synpase?

Once the vesicle holding a neurotransmitter merges with the presynaptic terminal membrane of the neuron, the neurotransmitter molecules are released into the synapse. They then diffuse across the synaptic cleft and bind with receptors on the postsynaptic membrane, opening specific ion channels there. After release neurotransmitter molecules may diffuse away from the synapse, may be broken down by an enzyme (ex. acetylcholinesterase), or may be taken up by a neuron via a membrane protein transporter. In any case, the effect of the neurotransmitter is brief as quick, prompt removal of the neurotransmitter terminates signal transmission. See diagram below, part A, #5.

The synthesis, packaging, secretion, and removal of neurotransmitters. (A) The life cycle of transmitter agents entails (1) neurotransmitter synthesis, (2) packaging into vesicles, (3) fusion of vesicles resulting in neurotransmitter release, and (4) activation of postsynaptic receptors. Neurotransmitters are then removed from the synaptic cleft (5). In many cases, the neurotransmitter and/or a breakdown product is reused for neurotransmitter synthesis. (B) Small-molecule neurotransmitters are synthesized at nerve terminals. The enzymes necessary for neurotransmitter synthesis are made in the cell body of the presynaptic cell (1) and are transported down the axon by slow axonal transport (2). Precursors are taken up into the terminals by specific transporters, and neurotransmitter synthesis and packaging take place within the nerve endings (3). After vesicle fusion and release (4), the neurotransmitter may be enzymatically degraded. The reuptake of the neurotransmitter (or its metabolites) starts another cycle of synthesis, packaging, release, and removal (5). (C) Peptide neurotransmitters, as well as the enzymes that modify their precursors, are synthesized in the cell body (1). Enzymes and propeptides are packaged into vesicles in the Golgi apparatus. During fast axonal transport of these vesicles to the nerve terminals (2), the enzymes modify the propeptides to produce one or more neurotransmitter peptides (3). After vesicle fusion and exocytosis, the peptides diffuse away and are degraded by proteolytic enzymes (4). © 2001 by Sinauer Associates, Inc. Source of figure and caption text: Figure 6.6 in Neuroscience, 2nd edition, edited by Dale Purves.

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