A glomerulus, a complex synaptic arrangement involving both chemical and electrical synapses, is depicted in Fig. 6.1B. Our understanding of chemical synapses primarily comes from studying two classic preparations: the frog neuromuscular junction (a synapse between a motor neuron and a muscle fiber) and the squid giant synapse (a synapse between a second-order neuron and third-order neurons that innervate the squid's mantle muscle). These preparations have provided valuable insights into synaptic transmission, especially for synapses in the mammalian CNS that use "classic" neurotransmitters. While much of the following discussion is based on results from these preparations, we will also highlight some differences in CNS synapses.

Gaseous transmitters, such as nitric oxide (NO), diffuse out of the cell of origin and directly into other cells. They can act within the originating cell or in distant cells. These transmitters bind to synaptic and extrasynaptic G protein-complex receptors, activating a variety of enzymes. Gaseous transmitters utilize both ionotropic and G protein-coupled receptors for their effects. On the other hand, small-molecule neurotransmitters like acetylcholine (ACh) and other similar molecules diffuse across the synaptic cleft and bind to postsynaptic receptors. These neurotransmitters are concentrated into vesicles by vesicle transporters and are released upon fusion of the vesicles with the plasma membrane of the presynaptic terminal.

Synaptic transmission at a chemical synapse follows a general sequence of events. Upon arrival of the action potential at the presynaptic terminal, the terminal depolarizes, leading to the opening of calcium (Ca++) channels. The subsequent increase in Ca++ concentration within the terminal triggers the fusion of neurotransmitter-containing vesicles with the plasma membrane. The released transmitter then diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. This binding results in the opening or closing of ion channels in the postsynaptic membrane, leading to changes in the membrane potential and resistance. These changes, known as excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs), respectively, alter the cell's excitability, which represents its likelihood of firing action potentials. The effects of the transmitter are short-lived, lasting only milliseconds, as reuptake and degradation mechanisms rapidly clear the transmitter from the synaptic cleft.
Fig. 6.1B shows a complex synaptic arrangement called a glomerulus that involves both chemical and electrical synapses among the participating elements.
Much of what we know about chemical synapses comes from the study of two classic preparations, the frog neuromuscular junction (the synapse from a motor neuron onto a muscle fiber) and the squid giant synapse (the synapse from a second-order neuron onto third-order neurons that innervate the muscle of the squid’s mantle; i.e., the motor neurons whose axons were used to characterize the conductances underlying the action potential [see ]). The principles governing transmission at these synapses mostly apply to synapses within the mammalian CNS as well, at least with regard to synapses using what are called the “classic” neurotransmitters (see the section mitters). Thus, much of the following discussion will be based on results from these two preparations; however, some differences in CNS synapses will also be pointed out.
3 Gaseous transmitters Arginine NO synthase Citrulline Mitochondria Peptides diffuse in extracellular space and bind to synaptic and extrasynaptic G protein–complex receptors Gaseous transmitters diffuse out of cell of origin and directly into other cells. They can act inside cell of origin or in cells distant from point of release G protein– coupled receptors NO Activates variety of enzymes Ionotropic and G protein– coupled receptors Acetyl CoA + Choline Reuptake by transporter 1 Small-molecule neurotransmitters AChAcetyl cholinesterase Other small-molecule neurotransmittersSmall-molecule neurotransmitters diffuse across synaptic cleft and bind to postsynaptic receptors Vesicle transporter concentrates neurotransmitter into vesicles Postsynaptic cell Presynaptic terminal Ca++ channels Large electron-dense vesicles NO O2 Nitrogen oxide (inactive) 2 Neuropeptides •Fig. 6.2 Schematicofachemicalsynapticterminalreleasingallthreemainclassesofneurotransmitter.Foreach,themechanismsofrelease,sitesofaction,andmechanismsforterminationofactivityareshown.Realsynapsesreleasetransmitterfromoneormoreclasses.
Synaptic transmission at a chemical synapse may be summarized as follows. Synaptic transmission is initiated by arrival of the action potential at the presynaptic terminal. The action potential depolarizes the terminal, which causes Ca++ channels to open. The subsequent rise in [Ca++] within the terminal triggers the fusion of vesicles containing neurotransmitter with the plasma membrane. The transmitter is then expelled into the synaptic cleft, diffuses across it, and binds to specific receptors on the postsynaptic membrane. Binding of transmitter to receptors then causes the opening (or less often, the closing) of ion channels in the postsynaptic membrane, which in turn results in changes in the potential and resistance of the postsynaptic membrane that alter the excitability of the cell. The changes in membrane potential of the postsynaptic cell are termed excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) (
Fig. 6.3 ), depending on whether they increase or decrease, respectively, the cell’s excitability, which can be defined as its probability of firing action potentials. The transmitter acts for only a very short time (milliseconds) because reuptake and degradation mechanisms rapidly clear the transmitter from the synaptic cleft.