Throughout the nervous system, and throughout life, activity-dependent elimination and reinforcement of synapses plays a fundamental part in adjusting the detailed anatomy of the neural network according to functional requirements. The importance of these processes, and their underlying rules, emerged half a century ago from a groundbreaking series of experiments on the developing visual system of young mammals.
In the brain of most mammals, axons relaying visual inputs from the two eyes are brought together in a specific neuronal layer in the visual region of the cerebral cortex. Here, they form two overlapping maps of the external visual field, one as perceived through the right eye, the other as perceived through the left. Although there may be a tendency for rightand left-eye inputs to be segregated even before synaptic communication begins, a large proportion of the axons carrying information from the two eyes at early stages form synapses together on shared target neurons in the visual cortex. A period of early electrical signaling activity, is quiet: cell C gets excited simultaneously: cell C gets excited synapse made by B on C synapses made by both A and B is weakened or eliminated on C are strengthened BB
Figure 21–84 Synapse modification and its dependence on electrical activity. experiments in several systems indicate that synapses are strengthened or weakened by electrical activity according to the rule shown in the diagram. the underlying principle appears to be that each excitation of a target cell tends to weaken any synapse where the presynaptic axon terminal has been quiet, but to strengthen any synapse where the presynaptic axon terminal has just been active. as a result, any synapse that is repeatedly weakened and rarely strengthened is eventually eliminated altogether.
Figure 21–85 Ocular dominance columns in the visual cortex of a monkey’s brain, and their sensitivity to visual experience. (a) Normally, stripes of cortical cells driven by the right eye alternate with stripes, of equal width, driven by the left eye. the stripes, set up before birth, are revealed here by injecting a radioactive tracer molecule into one eye, allowing time for this tracer to be transported to the visual cortex, and detecting radioactivity there by autoradiography, in sections cut parallel to the cortical surface. (B) If one eye is kept covered after birth, during the sensitive period of development, and thus deprived of visual experience, its stripes shrink and those of the active eye expand. In this way, the deprived eye may lose the power of vision almost entirely. (From
D.h. hubel, t.N. Wiesel and S. LeVay, Philos. Trans. R. Soc. Lond. B Biol. Sci. 278:377–409, 1977. With permission from the royal Society.) however, occurring spontaneously and independently in each retina before birth, leads to a remarkable pattern of ocular dominance columns in the visual cortex: stripes of cells driven by inputs from the right eye alternating with stripes driven by inputs from the left eye (Figure 21–85).
The basis for these phenomena became clear from ingenious experiments interfering artificially with visual experience and altering the coordination of electrical signaling in the two eyes. These studies, and many others subsequently, have highlighted a simple but profoundly important principle that seems to govern synapse reinforcement and elimination throughout the nervous system. When two (or more) neurons synapsing on the same target cell fire at the same time, they reinforce their connections to that cell; when they fire at different times, they compete, so that all but one of them tend to be eliminated. This firing rule is expressed in the catchphrase “neurons that fire together wire together.”
The firing rule provides a simple interpretation of the developmental phenomenon we have just described in the mammalian visual system. A pair of axons bringing information from neighboring sites in the left eye will frequently fire together, and therefore wire together, as will a pair of axons from neighboring sites in the right eye; but a right-eye axon and a left-eye axon will rarely fire together, and will instead compete. Indeed, if activity from both eyes is silenced using toxins that block axonal electrical activity or synaptic signaling, as described above, the inputs fail to segregate correctly.