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KEY CONCEPTS

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  • Synaptic transmission is a signal transduction process that begins with the action potential–dependent release of a neurotransmitter from a presynaptic terminal. The neurotransmitter then binds to and activates postsynaptic receptors that modify the electrical and biochemical properties of the 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 derivatives, such as adenosine and ATP.

  • Neurotransmitters are stored in small organelles called synaptic vesicles that fuse with the presynaptic terminal membrane and release their contents when an action potential invades the terminal and causes a rise in calcium due to activation of voltage-dependent calcium 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 glia by specialized proteins called plasma membrane transporters. A different family of transporters is responsible for pumping 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 the targets of bacterial toxins (eg, tetanus and botulinum toxin) and black widow spider venom (α-latrotoxin).

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

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INTRODUCTION

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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 different protein components of specific synapses. This chapter explores the biochemical basis of synaptic transmission and explains how this process is regulated.

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THE SYNAPSE

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Neurons are morphologically specialized to receive, process, and send information 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 a chemical signal in its nerve terminal, (2) this chemical signal is transmitted to another cell across a synapse, and (3) the chemical message received by the postsynaptic cell is converted into an electrical signal plus a range of chemical signals. It should be noted that a small percentage of synapses are gap junctions, morphologic connections between two neurons that permit the direct flow of electrical current ...

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