Synaptic plasticity

Most neurobiologists believe that memories are encoded in the pattern of cortical synaptic strengths, that is, in the effectiveness with which one neuron in the brain communicates with another at each of its synapses. As the human cortex contains about 1014 synapses (100 trillion), a lot of information could be stored. Understanding how memory works is, by general agreement, one of neurobiology’s central problems. Naturally, then, many neurobiologists are concerned with how synaptic strengths are regulated to store information; that is, they are interested in synaptic plasticity. Because long-term potentiation (LTP) and long-term depression (LTD) are the only mechanisms known for the persistent regulation of synaptic strength in neocortex, these two forms of synaptic plasticity have attracted great attention in recent years. The hippocampus has been identified as a brain region concerned with encoding memories and is therefore typically, but not exclusively, used to study LTP/LTD. The standard preparation for studies of cellular mechanisms of plasticity is slices of hippocampus. By stimulating a particular pathway (the Schaffer collaterals comprised of axons from pyramidal cells in a region of hippocampus known as ‘CA3’) and recording from any of the pyramidal cells in the hippocampal region designated ‘CA1’, the electrophysiologist can study direct (monosynaptic) excitatory synaptic connections (Figure 1). Suppose we stimulate the Schaffer collateral fibers and record from a typical CA1 pyramidal cell. If the Schaffer collaterals are stimulated once every minute, we find that the size of the postsynaptic response recorded from the CA1 pyramidal cell remains constant from stimulus to stimulus (Figure 2). Now we use the synapses heavily: stimulate 100 times in a second. After this intense stimulation the size of the postsynaptic response is larger and remains so for the remainder of the hour-long experiment; this maintained increase in postsynaptic size is LTP. A different kind of synaptic use can, however, have the opposite effect. Instead of giving the strong 100-stimulus burst, had we stimulated once every second for 15 minutes, we would have found that the postsynaptic response got smaller and stayed that way for the rest of the experiment; this is LTD. Magazine R151