PLASTICITY IN THE CNS-LEARNING FROM EXPERIENCE

PLASTICITY IN THE CNS­LEARNING FROM EXPERIENCE

The third principle of this chapter stated that the CNS responds to experi­ence by learning—that is, it reorganizes some of its neurochemistry and connections so that the experience is remembered. It is very important to understand that this plasticity is a broad concept. Not only does the CNS remember events that are consciously experienced, but it also changes in response to all sorts of signals, such as the constant presence of drugs.

The most familiar plasticity in the CNS is the simple remembering of experiences—faces, odors, names, classroom lectures, and lots more. The neurobiological mechanisms through which this kind of learning hap­pens are not completely understood, but we have some clues. One import­ant site of learning appears to be the synapse.

As discussed, synapses of nerve cells are quite complex, and there is extensive biochemical machinery in both the presynaptic and the post-synaptic areas. We think memory is built one synapse at a time: some synapses that are stimulated repeatedly change how they function (learn) and maintain that change for a long time. 'There is an electrical manifesta­tion of this learning that scientists call long-term potentiation (ITP). It is a long-lasting strengthening (potentiation) of the electrical signal between two neurons that occurs when the synapse between them is stimulated.

We're not sure how this happens, but it is likely through a series of bio­chemical changes in how the first neuron releases its neurotransmitter and/or in how the second neuron responds to the neurotransmitter. On the presynaptic side, a synapse could be strengthened by increasing the number of presynaptic terminals, by releasing more transmitters from the same number of terminals, or by a reduction in transmitter removal. On the postsynaptic side, strengthening could occur with an increase in the number of receptors, a change in the functional properties of the receptors, a change in how well the postsynaptic site is coupled to the remainder of the neuron, or a change in the biochemistry of the postsyn­aptic neuron. There is scientific controversy about the true mechanisms of um and the issue may not be clear for a number of years.

Almost every neuron can modify many aspects of its function to adapt to new conditions—by making more or less neurotransmitter, by chang­ing the number of receptors on the surface of its cells, by changing the number of molecules responsible for the passage of the electrical stimu­lus down the axon, and so forth. If a neural circuit is being overstimu­lated, it can reduce the stimulation by removing some of the receptors for the neurotransmitter stimulating it. Therefore, even if the neural cir­cuit is being sent lots of signals, they don't get through. Alternatively, if a neural circuit is receiving much less stimulation than usual, it can adapt by becoming more sensitive to each stimulus. This is how the brain stays

in balance.

This type of biochemical plasticity goes on all the time and is part of normal brain function. However, these same changes can cause abnormal brain function. For example, we think that the tremendous mood changes in depression might result from changing numbers of neurotransmitter receptors following changing stimulation of specific neurons in the brain. If neurons and synapses learn, do they also forget? The answer appears to be yes. We just described how stimulating a neural pathway in a certain way can cause it to "learn" to respond to stimulation differently. Stimulat­ing it in another way (slowly, and for a long time) can cause a process called depotentiation, which appears to be the opposite of long-term potentiation. Why is this interesting? Depotentiation could be quite important because it may represent the synaptic equivalent of amnesia. Depotentiation can be produced by prolonged slow activity or by very strong high-frequency activity, like that which occurs in seizures. It may be a protective mechanism by which the CNS prevents a seizure or brain trauma from encoding new information into the circuits. Again, it is almost certainly under the control of cell-signaling pathways and thus

could be manipulated by drugs.

This gradual change in the electrical strength of a connection seems subtle, but it makes intuitive sense that memories could form in this way. Can the brain actually change physically? We used to think that once a person was mature, the brain didn't change anymore. However, more and more research shows that actual changes in the shapes of neurons also can happen in response to earlier experiences. We know that the shape of certain neurons in the brain changes when different hormones become available. For example, at least in animals, treating them with hormones can stimulate the production of little protuberances, or "spines," on the dendrites of neurons. Other research has shown that synapses actually remodel themselves over time after different levels of activity. So, connec­tions actually get lost or remade. For example, prolonged stress seems to actually shrink the dendrite on neurons, perhaps explaining the cognitive difficulties people encounter during prolonged stressful periods.

It has been known for a long time that this happened in lower animals. For example, as songbirds learn new songs, the structure of certain parts of their brains changes. It was once thought that the brains of mammals did not have this type of structural plasticity. However, more recent stud­ies have shown similar changes in rats, and scientists think that they

probably occur in all mammals.

The most exciting recent development in neuronal plasticity is our understanding that the brain can actually make new neurons. This pro­cess, called neurogenesis, was long thought to occur mostly during prena­tal development, but now we find that it is happening in adult humans. Neurogenesis results from the conversion of neural stem cells into func­tional neurons. The rate of conversion seems to increase in response to injury or other pathologies and decrease in response to chronic stress. As with most neuroscience research, the data come primarily from animal experiments, usually rats, and as always, relevance to humans needs to be established.

There have been some intriguing findings regarding the effects of drugs on neurogenesis in animals. It appears that depression reduces neurogen­esis and subsequent treatment with antidepressants restores it. More rele­vant to this book, the laboratory of Fulton Crews at the University of North Carolina has made the startling discovery that binge exposure to alcohol dramatically suppresses rat neurogenesis, particularly in the ado­lescent forebrain, which is a brain area in rapid development. The poten­tial implications of this are enormous, because adolescents tend to be binge drinkers. Is this behavior impairing their brain development? What other drugs affect these processes? Does this really happen in humans? These questions should and will be answered by future research, but for now they alert us to the possibility that drug abuse could have profound effects on teenage brain development