1010 OverviewOverview ofof SynapticSynaptic Tr,Transmission Syn.apsesAre Either Electrical or Chemical electrical or chemical. Moreover, the strength of both Electrical Syn.apsesProvide Instantaneous Signal forms of synaptic transmission can be enhanced or di- 1I:ansmission minished by cellular activity. This pblsticity in nerve cells Gap-JunctionChannels Connect Communicating Cells at is crucial to memory and other higher brain functions. an Electrical Synapse In the brain, electrical synaptic transmission is ElectricalTransmission Allows the Rapid and rapid and rather stereotyped. Electrical synapses are SynchronousFiring of InterconnectedCells used primarily to send simple depolarizing signals; Gap JunctionsHave a Role in Glial Function and Disease they do not lend themselves to producing inhibitory ac- tions or making long-lasting changes in the electrical Chemical SynapsesCan Amplify Signals properties of postsynaptic cells. In contrast, chemical Chemical TransmittersBind to PostsynapticReceptors synapses are capable of more variable signaling and PostsynapticReceptors Gate Ion ChannelsEither Directly thus can produce more complex behaviors.They can or Indirectly mediate either excitatory or inhibitory actions in post- synaptic cells and produce electrical changes in the postsynaptic cell that last from milliseconds to many minutes. Chemical synapsesalso serve to amplify neu- W HATGIVES NERVE CELLS their special ability to ronal signals,so that evena smallpresynaptic nerve ter- communicate with one another so rapidly, minal can alter the responseof a large postsynaptic cell. over such great distances, and with such Becausechemical synaptic transmission is so central to tremendous precision? We have already seen how sig- understanding brain and behavior, it is examined in de- nals are propagated within a neuron, from its dendrites tail in Chapters 11, 12, and 13. and cell body to its axonal terminal. Beginning with this chapter we consider the cellular mechanisms for signal- ing betweenneurons. The point at which one neuron Synapses Are Either Electrical or Chemical communicates with another is called a synapse,and synaptic transmission is fundamental to many of the The term synapsewas introduced at the turn of the cen- processeswe consider later in the book, such as percep- tury by Charles Sherrington to describe the specialized tion, voluntary movement, and learning. zone of contact at which one neuron communicateswith Theaverage neuron forms about 1000synaptic con- another; this site had first been described histologically nections and receives even more, perhaps as many as (at the level of light microscopy) by Ram6n y Cajal. Ini- 10,000connections. The Purkinje cell of the cerebellum tially, all synapseswere thought to operate by means of receivesup to 100,000inputs. Although many of these electrical transmission. In the 1920s, however, Otto connections are highly specialized, all neurons make Loewi showed that acetylcholine (ACh), a chemicalcom- use of one of two basic forms of synaptic transmission: pound, conveys signals from the vagus nerve to the 176 Partm / ElementaryInteractions Between Neurons: Synaptic Thansmission Table 10-1 Distinguishing Properties of Electrical and Chemical Synapses Distance between Cytoplasmic pre- and continuity Type of postsynaptic cell between pre- and Ultrastructural Agent of Synaptic Direction of synapse membranes postsynaptic cells components transmission delay transmission Electrical 3.5nm Yes Gap-junction Ion current Vtrtually Usually channels absent bidirectional Chemical 20-40nm No Presynaptic Chemical Significant: Unidirec- vesicles and transmitter at least 0.3 tional active zones; IDS,usually postsynaptic 1-5 IDS receptors or longer heart. Loewi's discovery in the heart provoked consid- When physiological techniques improved in the erable debate in the 193Osover how chemical signals 19508and 1960sit becameclear that both forms of trans- could generateelectrical activities at other synapses,in- mission exist. Although most synapsesuse a chemical cluding nerve-muscle synapses and synapses in the transmitter, some operate purely by electrical means. brain. Oncethe fine structure of synapses was made visible Two schools of thought emerged, one physiological with the electron microscope, chemical and electrical and the other pharmacological. Each championed a sin- synapseswere found to have different morphologies. At gle mechanism for all synaptic transmission. The physi- chemical synapsesneurons are separatedcompletely by ologists, led by John Eccles (Sherrington's student), ar- a small space, the synaptic cleft. There is no continuity gued that all synaptic transmission is electrical, that the between the cytoplasm of one cell and the next. In con- action potential in the presynaptic neuron generates a trast, at electrical synapses the pre- and postsynaptic current that flows passively into the postsynaptic cell. cells communicate through special channels, the gap- The pharmacologists, led by Henry Dale, argued that junction channels,that serve as conduits between the cy- transmission is chemical, that the action potential in the toplasm of the two cells. presynaptic neuron leads to the release of a chemical The main functional properties of the two types of substancethat in turn initiates current flow in the post- synapses are summarized in Table 10-1. The most im- synaptic cell. portant differences can be observed by injecting current A Current flow at electrical synapses B Current flow at chemical synapses I Presyneptjc Postsynaptic Figure10-1 Currentflows differently at electricaland chem- B. At chemical synapsesall of the injected current escapes ical synapses. through ion channels in the presynapticcell. However,the re- A. At an electrical synapse some of the current injected into a sulting depolarizationof the cell activates the releaseof neuro- presynapticcell escapes through resting ion channels in the transmitter molecules packagedin synaptic vesicles (open cir- cell membrane.However, some current also flows into the clesl, which then bind to receptors on the postsynapticcell. postsynapticcell through specializedion channels. called gap- This binding opens ion channels,thus initiating a change in junction channels,that connect the cytoplasm of the pre- and membrane potential in the postsynaptic cell. postsynapticcells. Chapter10 I Overviewof SynapticTransmission 177 I A Experimentalsetup Current PresYl18ptic neuron: Injection Ieter8I gie~ fiber Recordng---- Iecording Cutr8nt~ injection Figure 10-2 Electrical synaptic transmission was first voltage are placed within both the p(f~ and postsynapticcells. demonstrated to occur at the giant motor synapse in the B. Transmissionat an electrical synapse is virtually instant&- crayfish. (Adaptedfrom Furshpanand Potter 1957 and 1959.) neous-the postsynapticresponse follows presynapticstimula- A. The presynapticneuron is the lateral giant fiber running tion in a fraction of a millisecond.The dashed line shows how down the nerve cord. The postsynaptic neuron is the motor the responsesof the two cells correspond in time. In contrast. fiber.which projectsfrom the cell bodyin the ganglionto the at chemical synapsesthere ia a delay between the pre- and I periphery.The electrodes for passing current and for recording postsynaptic potentials (see Figure 1~7). j into the presynaptic cell to elicit a signal (Figure to-t). external membrane of the postsynaptic ceIL which has a 1 At both types of synapses the current flows outward high resistance(Figure 10-1B).Instead, the action poten- C acrossthe presynaptic cell membrane. This current de- tial in the presynaptic neuron initiates the release of a 1 posits a positive charge on the inside of the presynaptic chemical transmitter, which diffuses acrossthe synaptic c cell membrane, reducing its negative charge and cleft to interact with receptors on the membrane of the t thereby depolarizing the cell (seeChapter 8). postsynaptic cell. Receptor activation causesthe cell ei- At electrical synapses the gap-junction channels ther to depolarize or to hyperpolarize. t that connect the pre- and postsynaptic cells provide a 14 low-resistance (high conductance) pathway for electri- C cal current to flow between the two cells. Thus, some of Electrical Synapses Provide Instantaneous tJ the current injected in the presynaptic cell flows Signal Transmission tJ through these channels into the postsynaptic cell. This c current deposits a positive charge on the inside of the At electrical synapses the current that depoJarizesthe D membrane of the postsynaptic cell and depolarizes it. postsynaptic cell is generated directly by the voltage- T The current then flows out through resting ion channels gated ion channels of the presynaptic cell. Thus these it in the postsynaptic cell (Figure to-tA). H the depolariza- channels not only have to depolarize the presynaptic ti tion exceeds threshold, voltage-gated ion channels in cell above the threshold for an action potential, they t1 the postsynaptic cell will open and generate an action must also generate sufficient ionic current to produce a P potential. change in potential in the postsynaptic cell. To generate At chemical synapses there is no direct low-resis- such a large current, the presynaptic terminal has to be ta tance pathway between the pre- and postsynaptic cells. large enough for its membrane to contain a large num- T Thus, current injected into a presynaptic cell flows out ber of ion channels. At the same time, the postsynaptic 01 of the cell's resting