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Introduction

LIKE SYNAPTIC TRANSMISSION at the neuromuscular junction, most rapid signaling between neurons in the central nervous system involves ionotropic receptors in the postsynaptic membrane. Thus, many principles that apply to the synaptic connection between the motor neuron and skeletal muscle fiber at the neuromuscular junction also apply in the central nervous system. Nevertheless, synaptic transmission between central neurons is more complex for several reasons.

First, although most muscle fibers are typically innervated by only one motor neuron, a central nerve cell (such as pyramidal neurons in the neocortex) receives connections from thousands of neurons. Second, muscle fibers receive only excitatory inputs, whereas central neurons receive both excitatory and inhibitory inputs. Third, all synaptic actions on muscle fibers are mediated by one neurotransmitter, acetylcholine (ACh), which activates only one type of receptor (the ionotropic nicotinic ACh receptor). A single central neuron, however, can respond to many different types of inputs, each mediated by a distinct transmitter that activates a specific type of receptor. These receptors include ionotropic receptors, where binding of transmitter directly opens an ion channel, and metabotropic receptors, where transmitter binding indirectly regulates a channel by activating second messengers. As a result, unlike muscle fibers, central neurons must integrate diverse inputs into a single coordinated action.

Finally, the nerve–muscle synapse is a model of efficiency—every action potential in the motor neuron produces an action potential in the muscle fiber. In comparison, connections made by a presynaptic neuron onto a central neuron are only modestly effective—in many cases at least 50 to 100 excitatory neurons must fire together to produce a synaptic potential large enough to trigger an action potential in postsynaptic neurons.

The first insights into synaptic transmission in the central nervous system came from experiments by John Eccles and his colleagues in the 1950s on the synaptic inputs onto spinal motor neurons that control the stretch reflex, the simple behavior we considered in Chapter 3. The spinal motor neurons have been particularly useful for examining central synaptic mechanisms because they have large, accessible cell bodies and, most important, they receive both excitatory and inhibitory connections and therefore allow us to study the integrative action of the nervous system at the cellular level.

Central Neurons Receive Excitatory and Inhibitory Inputs

To analyze the synapses that mediate the stretch reflex, Eccles activated a large population of axons of the sensory cells that innervate the stretch receptor organs in the quadriceps (extensor) muscle (Figure 13–1A,B). Nowadays the same experiments can be done by stimulating a single sensory neuron.

Figure 13–1

The combination of excitatory and inhibitory synaptic connections mediating the stretch reflex of the quadriceps muscle is typical of circuits in the central nervous system.

A. A sensory neuron activated by a stretch receptor (muscle spindle) at the extensor (quadriceps) muscle makes an excitatory connection with an extensor motor ...

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