Long-term potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons.[2] The opposite of LTP is long-term depression, which produces a long-lasting decrease in synaptic strength.
It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength. As memories are thought to be encoded by modification of synaptic strength,[3] LTP is widely considered one of the major cellular mechanisms that underlies learning and memory.[2][3]
LTP was discovered in the rabbit hippocampus by Terje Lømo in 1966 and has remained a popular subject of research since. Many modern LTP studies seek to better understand its basic biology, while others aim to draw a causal link between LTP and behavioral learning. Still, others try to develop methods, pharmacologic or otherwise, of enhancing LTP to improve learning and memory. LTP is also a subject of clinical research, for example, in the areas of Alzheimer's disease and addiction medicine.
Types
Since its original discovery in the rabbit hippocampus, LTP has been observed in a variety of other neural structures, including the cerebral cortex,[18] cerebellum,[19] amygdala,[20] and many others. Robert Malenka, a prominent LTP researcher, has suggested that LTP may even occur at all excitatory synapses in the mammalian brain.[21]
Different areas of the brain exhibit different forms of LTP. The specific type of LTP exhibited between neurons depends on a number of factors. One such factor is the age of the organism when LTP is observed. For example, the molecular mechanisms of LTP in the immature hippocampus differ from those mechanisms that underlie LTP of the adult hippocampus.[22] The signalling pathways used by a particular cell also contribute to the specific type of LTP present. For example, some types of hippocampal LTP depend on the NMDA receptor, others may depend upon the metabotropic glutamate receptor (mGluR), while still others depend upon another molecule altogether.[21] The variety of signaling pathways that contribute to LTP and the wide distribution of these various pathways in the brain are reasons that the type of LTP exhibited between neurons depends only in part upon the anatomic location in which LTP is observed. For example, LTP in the Schaffer collateral pathway of the hippocampus is NMDA receptor-dependent - this was proved by the application of AP5, an antagonist to the NMDA receptor, which prevented LTP in this pathway.[23] Conversely, LTP in the mossy fiber pathway is NMDA receptor-independent, even though both pathways are in the hippocampus.[24]
The pre- and postsynaptic activity required to induce LTP are other criteria by which LTP is classified. Broadly, this allows classification of LTP into Hebbian, non-Hebbian, and anti-Hebbian mechanisms. Borrowing its name from Hebb's postulate, summarized by the maxim that "cells that fire together wire together," Hebbian LTP requires simultaneous pre- and postsynaptic depolarization for its induction.[25] Non-Hebbian LTP is a type of LTP that does not require such simultaneous depolarization of pre- and postsynaptic cells; an example of this occurs in the mossy fiber hippocampal pathway.[26] A special case of non-Hebbian LTP, anti-Hebbian LTP explicitly requires simultaneous presynaptic depolarization and relative postsynaptic hyperpolarization for its induction.[27]
Owing to its predictable organization and readily inducible LTP, the CA1 hippocampus has become the prototypical site of mammalian LTP study. In particular, NMDA receptor-dependent LTP in the adult CA1 hippocampus is the most widely studied type of LTP,[21] and is therefore, the focus of this article.