Barry W. Connors
Neurons receive, combine, transform, store, and send information
Neurons have arguably the most complex job of any cell in the body. Consequently, they have an elaborate morphology and physiology. Each neuron is an intricate computing device. A single neuron may receive chemical input from tens of thousands of other neurons. It then combines these myriad signals into a much simpler set of electrical changes across its cellular membrane. The neuron subsequently transforms these ionic transmembrane changes according to rules determined by its particular shape and electrical properties and transmits a single new message through its axon, which itself may contact and inform hundreds of other neurons. Under the right circumstances, neurons also possess the property of memory; some of the information coursing through a neuron's synapses may be stored for periods as long as years.
This general scheme of neuronal function applies to most neurons in the vertebrate nervous system. However, the scheme is endlessly variable. For example, each region of the brain has several major classes of neurons, and each of these classes has a physiology adapted to perform specific and unique functions. In this chapter, the general principles of neuronal function are outlined, and the almost unlimited variability contained within the general schema is discussed.
Neural information flows from dendrite to soma to axon to synapse
Numerous dendrites converge on a central soma, or cell body, from which a single axon emerges and branches multiple times (see Fig. 10-1). Each branch culminates at a presynaptic terminal that contacts another cell. In most neurons, dendrites are the principal synaptic input sites, although synapses may also be found on the soma, on the axon hillock (the region of the soma neighboring the axon), or even directly on the axons. In some primary sensory neurons, the dendrites themselves are transducers of environmental energy. Regardless of their source, signals—in the form of voltage changes across the membrane—typically flow from dendrites to soma to axon and finally to synapses on the next set of cells. Under some circumstances electrical signals may also propagate in the opposite direction, from the soma outward along dendrites to their tips.
Excitatory input to a neuron usually generates an inward flow of positive charge (i.e., an inward current) across the dendritic membrane. Because the interior of a resting neuron is polarized negatively with respect to the external environment, this inward current, which makes the membrane voltage more positive (i.e., less negative), is said to depolarize the cell. Conversely, inhibitory input to a neuron usually generates an outward current and, thus, hyperpolarization.
If the neuron receives its input from a neighboring cell through a chemical synapse, neurotransmitters trigger currents by activating ion channels. If the cell is a sensory neuron, environmental stimuli (e.g., chemicals, light, mechanical deformation) activate ion channels and produce a flow of current. The change in membrane potential (Vm) caused by the flow of charge is called a postsynaptic potential (PSP) if it is generated at the postsynaptic membrane by a neurotransmitter and a receptor potential if it is generated at a sensory nerve ending by an external stimulus. In the case of synaptic transmission, the postsynaptic Vm changes may be either positive or negative. If the neurotransmitter is excitatory and produces a depolarizing PSP, we refer to the PSP as an excitatory postsynaptic potential (EPSP; see p. 210). On the other hand, if the neurotransmitter is inhibitory and produces a hyperpolarizing PSP, the PSP is an inhibitory postsynaptic potential (IPSP). In all cases, the stimulus produces a Vm change that may be graded from small to large depending on the strength or quantity of input stimuli (see p. 174). Stronger sensory stimuli generate larger receptor potentials; similarly, more synapses activated together generate larger PSPs. A graded response is one form of neural coding whereby the size and duration of the input are encoded as the size and duration of the change in the dendritic Vm.
The synaptic (or receptor) potentials generated at the ends of a dendrite are communicated to the soma, usually with substantial attenuation of the signal (Fig. 12-1A). Extended cellular processes such as dendrites behave like leaky electrical cables (see pp. 201–203). As a consequence, dendritic potentials usually decline in amplitude before reaching the soma. As an EPSP reaches the soma, it may also combine with EPSPs arriving via other dendrites on the cell; this behavior is a type of spatial summation and can lead to EPSPs that are substantially larger than those generated by any single synapse (see Fig. 12-1B, C). Temporal summation occurs when EPSPs arrive rapidly in succession; when the first EPSP has not yet dissipated, a subsequent EPSP tends to add its amplitude to the residual of the preceding EPSP (see Fig. 12-1D).
FIGURE 12-1 Spatial versus temporal summation of EPSPs.
The tendency for synaptic and receptor potentials to diminish with distance along a dendrite puts significant limitations on their signaling abilities. If nothing else happened, these depolarizing potentials would simply dwindle back to the resting membrane potential as they spread through the soma and down into the axon. At best, this passive signal might be carried a few millimeters, clearly inadequate for commanding a toe to wiggle when the axon of the motor neuron stretching from the spinal cord to the muscles moving the foot might be 1000 mm long. Some amplification is therefore necessary for certain inputs to generate effective signals to and from the central nervous system (CNS). Amplification is provided in the form of regenerating action potentials. If the Vm change in the soma is large enough to reach the threshold voltage (see p. 173), the depolarization may trigger one or more action potentials between the soma and axon, as shown in Figure 12-1B to D. Action potentials are large, rapid fluctuations in Vm. As described in Chapter 7, an action potential is an efficient, rapid, and reliable way to carry a signal over long distances. However, notice that generation of action potentials entails another transformation of neuronal information: the neuron converts the graded-voltage code of the dendrites (i.e., the PSPs) to a temporal code of action potentials in the axon. The initiation site for action potentials in many types of neurons is the axon initial segment, the first stretch of unmyelinated axon past the soma.
Action potentials are fixed in amplitude, not graded, and have uniform shape. So how is information encoded by action potentials? This question has no simple answer and is still hotly debated. Because one axonal spike looks like another (with slight exceptions), neurons can vary only the number of spikes and their timing. For a single axon, information may be encoded by the average rate of action potential firing, the total number of action potentials, their temporal pattern, or some combination of these mechanisms. Figure 12-1 illustrates that as the synaptic potential in the soma increases in size, the resultant action potentials occur more frequently, and the burst of action potentials in the axon lasts longer. Notice also that by the time the signal has propagated well down the axon, the transformation has become complete—the graded potential has waned and vanished, whereas the action potentials have retained their size, number, and temporal pattern. The final output of the neuron is entirely encoded by these action potentials. When action potentials reach axonal terminals, they may trigger the release of a neurotransmitter at the next set of synapses, and the cycle begins again.