Long-Term Potentiation

Long-term potentiation (LTP) is a long-lasting strengthening of synaptic transmission that is triggered by brief periods of high-frequency synaptic stimulation. Other patterns of stimulation can produce a long-term weakening of synapses, a process termed long-term depression (LTD) or depotentiation. Synapses thus have a stable strength that can be bi-directionally modified in an activity-dependent manner. There are different forms of LTP at different brain synapses. This article focuses on LTP found at glutamatergic synapses in the CA1 region of the hippocampus, the most studied form of LTP. A typical experiment starts by measuring the strength of a group of synapses. This is done by firing a single action potential in some of the axons that enter this region. These axons make synapses with pyramidal cells and generate an excitatory postsynaptic potential (EPSP). The collective strength of the synapses is defined by the magnitude of the average EPSP. LTP is then induced by stimulating the axons to fire at high frequency (typically 100 Hz for 1 s), a stimulus referred to as a tetanus. Remarkably, this brief tetanus causes a long-lasting potentiation of the strength of the synapses. The size of the EPSP typically increases by 50%–100%, but can rise by as much as 800% in some situations. In the brain-slice preparation used for most studies, potentiation persists until the slice is no longer viable (5–12 h). LTP can also be induced in living animals, where it can persist for at least a year (1). The evidence that such changes in synaptic strength are actually involved in memory has strengthened in recent years. Studies have examined the effect of a learning experience on synapses in the hippocampus. Two groups (67, 225) have demonstrated that learning induces an LTP-like process, which reduces the subsequent ability to experimentally induce LTP at these synapses. This occlusion suggests that learning-induced and experimentally-induced potentiation affect the same