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  • Synaptic transmission is a signal transduction process that begins with action potential–dependent neurotransmitter release from a presynaptic nerve terminal. The neurotransmitter then binds to and activates postsynaptic receptors on a nearby neuron that modify the electrical and biochemical properties of that postsynaptic cell.

  • The major classes of neurotransmitters are amino acid transmitters, such as glutamate and GABA; monoamines, including dopamine, norepinephrine, and serotonin; acetylcholine; peptides; diffusible gases, such as nitric oxide; lipid–derived molecules, such as endocannabinoids; and nucleosides and their derivatives, such as adenosine and ATP.

  • Most neurotransmitters are stored in small organelles called synaptic vesicles that fuse with the presynaptic terminal plasma membrane and release their contents when an action potential invades the terminal and causes a rise in Ca2+ due to activation of voltage–gated Ca2+ channels.

  • A single neurotransmitter typically activates several different subtypes of receptors.

  • Neurotransmitter receptors are classified as ligand–gated ion channels or G protein–coupled receptors.

  • After being released, most neurotransmitters are transported back into the presynaptic terminal or into nearby glia by specialized proteins called plasma membrane transporters. A different family of transporters is responsible for pumping and concentrating neurotransmitter into synaptic vesicles.

  • Neurotransmitter transporters are important targets of many antidepressant medications and psychostimulant drugs such as cocaine and amphetamines.

  • The proteins that are responsible for the fusion of synaptic vesicles with the presynaptic plasma membrane, a process known as exocytosis, have been identified and extensively characterized. Some of these proteins are targets of bacterial toxins (eg, tetanus and botulinum toxin).

  • After exocytosis, synaptic vesicles are recycled and used again by repackaging them with neurotransmitter.

When we think, feel, or move, information passes rapidly between neurons across specialized gaps called synapses. When we learn and remember, synapses undergo significant activity–dependent alterations. Given the centrality of synaptic transmission to the function of the nervous system, it is not surprising that the large majority of drugs used to treat neuropsychiatric illnesses act on various protein components of specific synapses. This chapter explores the biochemical basis of synaptic transmission and explains how this process is regulated.


Neurons are morphologically specialized to receive, process, and send information (Figure 3-1). As discussed in Chapter 2, the key structure across which information is transferred, by use of chemical neurotransmitters, is the synapse. Synaptic transmission is a result of three types of processes that convert electrical information into a chemical signal and then back again: (1) electrical information in the axon of a presynaptic neuron is converted to the release of a chemical signal from a nerve terminal, (2) this chemical signal—called a neurotransmitter—diffuses across a synapse to a nearby postsynaptic neuron, and (3) the chemical message is sensed by the postsynaptic cell through specialized receptor proteins, which then convert the information into an electrical signal plus a range of chemical signals. It should be noted that a small percentage of connections ...

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