Long-Term Depression Is the Converse of Long-Term Potentiation

We noted early in Chapter 15 that negative as well as positive changes can store information in the nervous system. Several investigators have shown that long-term depression (LTD) may play a role in memory (Bear and Malenka, 1994; Linden, 1994). LTD is the converse of LTP: a lasting decrease in the magnitude of responses of neurons after afferent cells have been activated with electrical stimuli of relatively low frequency.

In the CA1 region of the hippocampus, the induction of LTD appears to require the entry of Ca2+ through NMDA receptors, just as the induction of LTP does. How can the entry of Ca2+ call for the induction of both LTP and LTD? The critical factor is the amount of change of Ca2+. A large surge of Ca2+ in the postsynaptic neuron triggers the induction of LTP by activating Ca2+-dependent protein kinases. In contrast, small increases of postsynaptic Ca2+ induce LTD by selectively activating the opposite kind of enzyme—protein phosphatases that catalyze dephosphorylation, which is the removal of phosphate groups (Lisman, 1989; Mulkey et al., 1993). Different sites on the AMPA receptor are phosphorylated or dephosphorylated in LTP and LTD, respectively (H.-K. Lee et al., 2000).