The nature and causes of hippocampal long-term potentiation

Abstract

One of the most fascinating features of the hippocampus is its capacity for plasticity. Long-term potentiation (LTP), a stable facilitation of synaptic potentials after high-frequency synaptic activity, is very prominent in hippocampus and is a leading candidate memory storage mechanism. Here, we discuss the nature and causes of LTP and relate them to endogenous rhythmic neuronal activity patterns and their potential roles in memory. Anatomical studies indicate that LTP is accompanied by postsynaptic structural modifications while pharmacological studies strongly suggest that LTP is not due to an increase in presynaptic transmitter release. In field CA1, LTP induction appears to be triggered by a postsynaptic influx of calcium through NMDA receptor-linked channels. Possible roles of several calcium-sensitive enzyme systems in LTP are discussed and it is argued that activation of a calcium-dependent protease (calpain) could produce the structural changes linked to LTP. Rhythmic bursting activity is highly effective in inducing LTP and it is argued that the endogenous hippocampal theta rhythm plays a role in LTP induction in vivo. Finally, studies indicate that LTP and certain types of memory share a common pharmacology and the use of electrical brain stimulation as a sensory cue suggests that LTP develops when the significance of that cue is learned.