Electrical signals from dendrites converge and summate at the soma. Although action potentials themselves often appear first at the nearby axon hillock and initial segment of the axon, the large variety of ion channels in the soma and proximal dendritic membranes is critically important in determining and modulating the temporal patterns of action potentials that ultimately course down the axon.
Neurons can transform a simple input into a variety of output patterns
Neurophysiologists have sampled the electrical properties of many different types of neurons in the nervous system, and one general conclusion seems safe: no two types behave the same. The variability begins with the shape and height of individual action potentials. Most neurons within the CNS generate action potentials in the conventional way (see Fig. 7-4). Fast voltage-gated Na+ channels (see pp. 185–187) generate a strong inward current that depolarizes the membrane from rest, usually in the range of –60 to –80 mV, to a peak that is usually between +10 and +40 mV. This depolarization represents the upstroke of the action potential. The Na+ channels then quickly inactivate and close, and certain K+ channels (often voltage-gated, delayed outward-rectifier channels; see pp. 193–196) open and thus cause Vm to fall and terminate the spike. However, many neurons have somewhat different spike-generating mechanisms and produce spikes with a range of shapes. N12-1 Although a fast Na+ current invariably drives the fast upstroke of neuronal action potentials, an additional fast Ca2+ current (see pp. 188–189) can frequently occur and, if it is large enough, broaden the spike duration. Adding to the complexity, individual neurons usually have more than one type of Na+ current and multiple types of Ca2+ currents. The greatest variability occurs in the repolarization phase of the spike. Many neurons are repolarized by several other voltage-gated K+ currents in addition to the delayed outward-rectifier K+ current, and some also have K+ currents carried by one or more channels that are rapidly activated by the combination of membrane depolarization and a rise in [Ca2+]i (see pp. 196–197).
Shapes of Action Potentials in Various Neurons
Contributed by Barry Connors
EFIGURE 12-1 Range of shapes of action potentials in various neurons.
More dramatic variations occur in the repetitive spiking patterns of neurons, observed when the duration of a stimulus is long. One way to illustrate this principle is to apply a simple continuous stimulus (a current pulse, for example) to a neuron and to measure the neuron's output (the number and pattern of action potentials fired at its soma). The current pulse is similar to a steady, strong input of excitatory synaptic currents. The transformation from stimulus input to spiking output can take many different forms. Some examples are shown in Figure 12-4, which illustrates recordings from three types of neurons in the cerebral cortex. In response to a sustained current stimulus, some cells generate a rapid train of action potentials that do not adapt (see Fig. 12-4A); that is, the spikes occur at a regular interval throughout the current pulse. Other cells fire rapidly at first but then adapt strongly (see Fig. 12-4B); that is, the spikes gradually become less frequent during the current pulse. Some cells fire a burst of action potentials and then stop firing altogether, and still others generate rhythmic bursts of action potentials that continue as long as the stimulus (see Fig. 12-4C). These varied behaviors are not arbitrary but are characteristic of each neuron type, and they are as distinctive as each cell's morphology. They are also an intrinsic property of each neuron; that is, a neuron's fundamental firing pattern is determined by the membrane properties of the cell and does not require fluctuations in synaptic input. Of course, synaptic input may also impose particular firing patterns on a neuron. When a neuron is operating in situ, its firing patterns are determined by the interaction of its intrinsic membrane properties and synaptic inputs.
FIGURE 12-4 Spiking patterns.
Rhythmically bursting cells are particularly interesting and occur in a variety of places in the brain. As described on pages 397–398, they may participate in the central circuits that generate rhythmic motor output for behavior such as locomotion and respiration. Cells that secrete peptide neurohormones, such as the magnocellular neurons of the hypothalamus, are also often characterized by rhythmic bursting behavior. These cells release either arginine vasopressin to control water retention (see pp. 844–845) or oxytocin to control lactation (see p. 1150). Rhythmic bursting is a more effective stimulus for the synaptic release of peptides than are tonic patterns of action potential. It may be that the bursting patterns and the Ca2+ currents that help drive them can elicit the relatively high [Ca2+]i necessary to trigger the exocytosis of peptide-containing vesicles (see pp. 219–221). One additional role of rhythmically bursting neurons is to help drive the synchronous oscillations of neural activity in forebrain circuits (i.e., thalamus and cortex) during certain behavioral states, particularly sleep.
Although it has been difficult to prove, the diverse electrical properties of neurons are probably adapted to each cell's particular functions. For example, in the first stage of auditory processing in the brain, cranial nerve VIII axons from the cochlea innervate several types of neurons in the cochlear nucleus of the brainstem. The axons provide similar synaptic drive to each type of neuron, yet the output from each neuron type is distinctly different. Some are tuned to precise timing and respond only to the onset of the stimulus and ignore anything else; some respond, pause, and respond again; others chop the ongoing stimulus into a more rhythmic output; and still other cells transform the input very little. The mechanisms for this range of transformations include both synaptic circuitry and the diverse membrane properties of each cell type. The different properties allow some cells to be particularly well tuned to specific features of the stimulus—its onset, duration, or amplitude modulation—and they can then communicate this signal to the appropriate auditory nuclei for more complex processing.
Intrinsic firing patterns are determined by a variety of ion currents with relatively slow kinetics
What determines the variety of spiking patterns in each type of neuron, and why do neurons differ in their intrinsic patterns? The key is a large set of ion channel types that have variable and often relatively slow kinetics compared with the quick Na+ and K+ channels that shape the spike. For a discussion of the properties of such channels, see p. 182. Each neuron expresses a different complement of these slow channels and has a unique spatial arrangement of them on its dendrites, soma, and axon initial segment. The channels are gated primarily by membrane voltage and [Ca2+]i, and a neuron's ultimate spiking pattern is determined by the net effects of the slow currents that it generates. We provide three examples of systems that have been studied in detail.
1. A neuron with only fast voltage-gated Na+ channels and delayed-rectifier K+ channels will generate repetitive spikes when it is presented with a long stimulus. The pattern of those spikes will be quite regular over time, as for the particular type of cerebral cortical interneuron that we have already seen in Figure 12-4A.
2. If the neuron also has another set of K+ channels that activate only very slowly, the spiking pattern becomes more time dependent: the spiking frequency may initially be very high, but it adapts to progressively lower rates as a slow K+ current turns on to counteract the stimulus, as shown for the small pyramidal cell in Figure 12-4B. The strength and rate of adaptation depend strongly on the number and properties of the fast and slow K+ channels.
3. A neuron, by exploiting the interplay between two or more voltage-gated currents with relatively slow kinetics, can generate spontaneous rhythmic bursting—as in the case of the large pyramidal neuron in Figure 12-4C—even without ongoing synaptic activity to drive it.