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 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. (shrink)

The neurophysiological phenomenon of LTP (long term potentiation) is considered by many to represent an adequate mechanism for acquiring or storing memories in the mammalian brain. In our target article, we reviewed the various arguments put forth in support of the LTP/memory hypothesis. We concluded that these arguments were inconsistent with the purported data base and proposed an alternative interpretation that we suggested was at least as compatible with the available data as the more widely held view. In doing so, (...) we attempted to illustrate that the inadequacy of present experimental designs did not permit us to distinguish between equally viable hypotheses. In the four years since we wrote the first draft of our target article, hundreds of additional studies on LTP have been published and their results have been incorporated into current theories about memory. A diverse group of commentators responded to our target article with their own theories of how memories might be stored in the brain, some of which rely on LTP. Some commentators doubted whether memories can be stored through modifications of synaptic strength. Some assert that it will never be possible to understand the neural mechanisms of memory; still others remain hopeful that we will accomplish some semblance of a resolution, provided we appreciate LTP's role in a subset of seemingly amorphous memory systems. In summary, although it is commonly written that “LTP is a memory storage device,” the divergence of views among the commentators suggests, at least as strongly as our target article, that such conviction is unwarranted and fails to acknowledge both the lack of consensus regarding the role of LTP in memory and the complexity of the phenomenon of memory itself. (shrink)

Long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy that many consider the best candidate currently available for a neural mechanism of memory formation and/or storage in the mammalian brain. In our target article, LTP: What's learning got to do with it?, we concluded that there was insufficient data to warrant such a conclusion. In their commentaries, Jeffery and Zhadin raise a number of important issues that we did not raise, both for and against the hypothesis. Although we agree (...) with a number of these issues, we maintain that there remains insufficient evidence that LTP is a memory mechanism. (shrink)