Long-term potentiation: What's learning got to do with it?

Abstract

Long-term potentiation (LTP) is operationally defined as a long-lasting increase in synaptic efficacy following high-frequency stimulation of afferent fibers. Since the first full description of the phenomenon in 1973, exploration of the mechanisms underlying LTP induction has been one of the most active areas of research in neuroscience. Of principal interest to those who study LTP, particularly in the mammalian hippocampus, is its presumed role in the establishment of stable memories, a role consistent with “Hebbian” descriptions of memory formation. Other characteristics of LTP, including its rapid induction, persistence, and correlation with natural brain rhythms, provide circumstantial support for this connection to memory storage. Nonetheless, there is little empirical evidence that directly links LTP to the storage of memories. In this target article we review a range of cellular and behavioral characteristics of LTP and evaluate whether they are consistent with the purported role of hippocampal LTP in memory formation. We suggest that much of the present focus on LTP reflects a preconception that LTP is a learning mechanism, although the empirical evidence often suggests that LTP is unsuitable for such a role. As an alternative to serving as a memory storage device, we propose that LTP may serve as a neural equivalent to an arousal or attention device in the brain. Accordingly, LTP may increase in a nonspecific way the effective salience of discrete external stimuli and may thereby facilitate the induction of memories at distant synapses. Other hypotheses regarding the functional utility of this intensely studied mechanism are conceivable; the intent of this target article is not to promote a single hypothesis but rather to stimulate discussion about the neural mechanisms underlying memory storage and to appraise whether LTP can be considered a viable candidate for such a mechanism.

Hippocampal and neocortical interactions during context discrimination: Electrophysiological evidence from the rat

“…LTP) also affect context learning (e.g. Shors and Matzel, 1997). These results not only support the hypothesis that hippocampus processes context information, but more specifically, they indicate that hippocampus plays a particularly salient role in the discrimination of meaningful contexts (Smith and Mizumori, 2006a).…”

Theta-Frequency Synaptic Potentiation in CA1In VitroDistinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats

“…This link has been strengthened by studies in which hippocampal LTP in aged rats was found to be related to individual differences in spatial learning ability (Barnes and McNaughton, 1985;Deupree et al, 1991;Davis et al, 1993;Bach et al, 1999). Such correlative studies reinforce the idea that the hippocampus plays a key role in spatial memory formation, but whether a selective deficit in LTP per se explains the spatial learning deficit in aged animals is unclear (Shors and Matzel, 1997;McEachern and Shaw, 1999).…”

Inhibition of learning and memory by general anesthetics

“…86,94 Long-term memory and LTP of synapses share many similar properties, as both are triggered rapidly and depend on the synthesis of new proteins, and they can last for many months. [94][95][96] Long-term potentiation may account for many types of learning, from the relatively simple classical conditioning that occurs in all animals [97][98][99] to the more complex higher-level cognition observed in humans. 94,100 The opposite process, long-term depression of synaptic strength, is also necessary and is normally involved in memory storage.…”