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Short-Term Synaptic Plasticity as a Switch for Weighting Important Neural Information
Summary: Charles Stevens uses electrophysiology, molecular biology, functional imaging, electron and light microscopy, comparative neuroanatomy, and theoretic approaches to elucidate how neuronal circuits compute.
Each nerve cell in the brain receives information from something like 10,000 other neurons at specialized points of contact called synapses. These synapses can be classified into two mutually exclusive and immutable types, excitatory and inhibitory, with opposing effects. Activation of excitatory synapses tends to cause the receiving neuron to produce nerve impulses, and activation of inhibitory synapses tends to negate the action of excitatory synapses and to prevent nerve impulses. About 3/4 of the synapses are excitatory, and the total activation of synapses determines when nerve impulses are sent out to other neurons.
Although all synapses work basically the same way, they exhibit a wide range of strengths—the effectiveness with which excitatory synapses cause the production of nerve impulses and inhibitory synapses oppose nerve impulse production. Information sent to a nerve cell through strong synapses is emphasized, and so the strongest synapses mainly determine the output of a nerve cell and dominate the computations performed by neuronal circuits. As might be expected from the importance for brain function of synaptic strength, many neuronal mechanisms are available for modifying it. Some of these mechanisms cause persistent alterations in strength that can last months or years, whereas other mechanisms produce a transient change in synaptic strength that may last from a fraction of a second to many tens or hundreds of seconds. The collection of mechanisms that result in transient increases or decreases of strength is known as short-term plasticity.
Some of the most important types of short-term plasticity reflect, in a complex way, the history of a synapse's use. Thus, short-term plasticity provides a way for a neuron to emphasize or de-emphasize particular types of information according to the pattern of activation over the recent past; short-term plasticity, then, is thought of as a sort of history-dependent filter that selects what information will be most important in determining the output of a nerve cell.
Although the various forms of short-term synaptic plasticity have been intensively studied for many years, we know little about the precise role played by this plasticity in brain function. My laboratory set out to answer the question, "What is short-term synaptic plasticity good for?"
Our first step was to select a brain region to use for answering this question. For a variety of reasons, we selected the hippocampus, a specialized brain structure present in all mammals. Most of the neurons in the hippocampus are "place" cells: each place in the environment is assigned to different hippocampal nerve cells, and particular place cells produce nerve impulses only when the animal is in the part of its environment attached to those cells. The hippocampus has two main subparts (fields CA1 and CA3), and the place cells in one part (CA3) send nerve impulses to nerve cells in the second part (CA1). The pattern of nerve impulses produced by place cells is very consistent: long periods of silence (when the animal is not in the cell's "place") are interspersed between bursts of nerve impulses (when the animal moves through the cell's place). One reason, then, for selecting the hippocampus is that synapses onto cells in the second region (CA1) are activated by a particular characteristic pattern of nerve impulses that is well known.
A second reason for selecting the hippocampus is that recordings from place cells in freely moving animals are available. This means that we can play the same sort of nerve impulse pattern into a synapse that the synapse would experience during natural brain function.
A third advantage of the hippocampus is that, when excitatory synapses are activated with a particular temporal pattern, certain inhibitory synapses on the same cell experience the same pattern. This means that the properties of both excitatory and inhibitory synapses can be studied with the pattern of use that is typical of both (there are experimental ways of studying each type of synapse separately). The final advantage of the hippocampus is that brain slices can be made that keep the basic circuit intact so it can be easily studied in isolation.
The idea of our experiments, then, is to use patterns of nerve impulses that would normally activate the synapses we study, and to see what effect short-term plasticity has on the information being transmitted by the synapses. Since we know the meaning of the hippocampal neural signals, we should be able to determine what use short-term plasticity could have in modifying this information.
Although many types of short-term plasticity are recognized, we need, for present purposes, to focus on only two main types. The first type is termed augmentation. With each nerve impulse arrival at a synapse, augmentation accumulates and produces an increase in synaptic strength that dissipates over about a second.
The second main type of plasticity, depression, produces an accumulating decrement in synaptic strength that occurs with each use, and it also has a characteristic recovery time of around a second. Although many other plasticity mechanisms are known, we can describe the effects of short-term plasticity by just considering augmentation and depression.
Virtually all synapses in the brain exhibit short-term plasticity, but the properties differ from one type of neuron to another and even from one synapse to the next on a single nerve cell. In some cases, one type of plasticity will dominate and in other situations another type will be most important. With repeated use of a synapse, the strength might first increase (because of augmentation) and then greatly decrease (because of accumulating depression). The properties of short-term plasticity also vary with experimental conditions, such as pattern of use and temperature.
When we examined the response of hippocampal excitatory synapses that were activated with a natural pattern of nerve impulses, we found that augmentation dominated depression, so that when a burst of nerve impulses arrived at the synapse (as it would when the animal moved through that neuron's place field), the strength of the synapses was increased very rapidly by about twofold. It turns out that the synaptic strength is increased by about the same amount for any burst, so the effect of short-term plasticity at excitatory synapses is to double the strength of the signal that indicates the animal's position.
For the hippocampal inhibitory synapses, the reverse occurred: depression dominated, so that the inhibitory synaptic strength was decreased—and by the same amount—for any burst of nerve impulses that arrived at the inhibitory synapses. The changes in strength at inhibitory synapses exactly mirror, in reverse, the changes produced at excitatory synapses.
Because inhibitory synapses oppose the effect of excitatory synapses, short-term plasticity produced by a burst of activity—indicating a place field being occupied—acts like a switch that increases the effectiveness of the relevant place information by turning up the excitation and simultaneously turning down the opposing inhibition. In this situation, then, short-term plasticity has properties designed to give increased weight to place information.
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