Half a century legacy of long-term potentiation

In 1973, two papers from Bliss and Lømo and from Bliss and Gardner-Medwin reported that high-frequency synaptic stimulation in the dentate gyrus of rabbits resulted in a long-lasting increase in synaptic strength. This form of synaptic plasticity, commonly referred to as long-term potentiation (LTP), was immediately considered as an attractive mechanism accounting for the ability of the brain to store information. In this historical piece looking back over the past 50 years, we discuss how these two landmark contributions directly motivated a colossal research effort and detail some of the resulting milestones that have shaped our evolving understanding of the molecular and cellular underpinnings of LTP. We highlight the main features of LTP, cover key experiments that defined its induction and expression mechanisms, and outline the evidence supporting a potential role of LTP in learning and memory. We also briefly explore some ramifications of LTP on network stability, consider current limitations of LTP as a model of associative memory, and entertain future research orientations.