Long‐term potentiation and the mechanisms of memory

Abstract

AbstractLong‐term potentiation (LTP) is a cellular model of the memory processes that occurs in many nerve cells, usually at glutamatergic synapses. For this reason, glutamatergic synapses being the most abundant in the brain, LTP has been widely proposed as a mechanism of memory. Recent findings support this proposal and indicate that, indeed, LTP and memory processes share many properties. The initial steps of LTP and of memory involve the activation of glutamatergic NMDA (N‐methyl‐D‐asprtate) receptors, sensitive to AP5 (amino phosphono valerate), and are very sensitive to inhibition by GABAA (gamma amino butyric acid type A) receptor agonists. The phase that follows in the next 2 or 3 h depends on activation of protein kinase c (PKC) and is sensitive to inhibitors of this enzyme family. Like LTP, the underlying mechanism of memories persists for very long periods without the need of expression; and, like LTP, memories are readily expressed upon a reinstatement of the stimuli used in their induction, as is the case in test sessions. The expression of LTP and the expression of memory rely on AMPA (D,L‐alpha‐amino hydroxy methyl isoxazolone propionate) receptors sensitive to CNQX (cyano nitro quinoxaline dione). LTP occurs in many places within the brain, including the hippocampus, amygala, medial septum, and entorhinal cortex. the drug effects on memory mentioned above are seen when the drugs are infused into these brain regions. The region(s) involved depend on the type of memory being processed. These findings support the idea that LTP underlies memory acquisition, retention, and retrieval (the latter, at least for many days after acquisition) and may provide some clues for the development of drugs to alleviate memory disorders. © 1993 wiley‐Liss, Inc.