Long-term potentiation in the brain: a synaptic memory mechanism

One of the most remarkable properties of the mammalian brain is its ability to change in response to experience, a phenomenon referred to as neural plasticity. Synaptic plasticity specifically refers to activity-dependent changes in synaptic strength or efficacy of synaptic transmission. Synaptic plasticity enables us to acquire and perform different sensory, motor, and cognitive tasks, such as playing a musical instrument or learning a language. Synaptic plasticity is involved in the creation of memories and is a phenomenon that varies and evolves over an individual's lifetime. The most extensively studied forms of synaptic plasticity in the mammalian brain are long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission. Sixty years ago, an abstract by Terje Lømo first described a long-lasting synaptic potentiation induced by high-frequency afferent stimulation (Lømo T. Acta Physiol Scand 68: 128, 1966), and 7 years later the first full paper on LTP was published by Tim Bliss and Terje Lømo in the Journal of Physiology (Bliss TV, Lomo T. J Physiol 232: 331-356, 1973). Since then, "neuroplasticity" or "brain plasticity" has emerged as a central theme of research in neuroscience. Increasing evidence supports the supposition that LTP is a natural phenomenon that is directly involved in neurodevelopment and learning and memory processes. Additionally, different brain disorders seem to be due to alterations in brain plasticity. Since its discovery, thousands of papers have appeared describing the underlying mechanisms and demonstrating that LTP is a robust and general brain mechanism that exists in vivo in animals including humans. Currently, the field is dedicated to defining more precisely the functions in which LTP (and LTD) is involved, including development, learning, and memory, as well as their roles in brain disorders. Here, we describe the present state of the field. We foresee that important discoveries remain to be made with implications for the understanding of, and treatment of, brain disorders.