Long-Term Potentiation and Memory

Abstract

Lynch, MA. Long-Term Potentiation and Memory. Physiol Rev 84: 87–136, 2004; 10.1152/physrev.00014.2003.—One of the most significant challenges in neuroscience is to identify the cellular and molecular processes that underlie learning and memory formation. The past decade has seen remarkable progress in understanding changes that accompany certain forms of acquisition and recall, particularly those forms which require activation of afferent pathways in the hippocampus. This progress can be attributed to a number of factors including well-characterized animal models, well-defined probes for analysis of cell signaling events and changes in gene transcription, and technology which has allowed gene knockout and overexpression in cells and animals. Of the several animal models used in identifying the changes which accompany plasticity in synaptic connections, long-term potentiation (LTP) has received most attention, and although it is not yet clear whether the changes that underlie maintenance of LTP also underlie memory consolidation, significant advances have been made in understanding cell signaling events that contribute to this form of synaptic plasticity. In this review, emphasis is focused on analysis of changes that occur after learning, especially spatial learning, and LTP and the value of assessing these changes in parallel is discussed. The effect of different stressors on spatial learning/memory and LTP is emphasized, and the review concludes with a brief analysis of the contribution of studies, in which transgenic animals were used, to the literature on memory/learning and LTP.

The cyclic AMP phenotype of fragile X and autism

“…In a mouse study, rolipram-induced increases of cAMP reduce the spatial memory defects associated with aging (Bach, Barad et al 1999). The cAMP cascade is one of several implicated in studies of long term potentiation (LTP), a neuronal model of memory (Lynch 2004). LTP is considered a form of synaptic plasticity based on synaptic strengthening which is known to involve cAMP (Frey, Huang et al 1993;Weisskopf, Castillo et al 1994), AMPA receptors, and NMDA receptors.…”

The Selective 5-HT6 Receptor Antagonist Ro4368554 Restores Memory Performance in Cholinergic and Serotonergic Models of Memory Deficiency in the Rat

“…It has been suggested that this effect may reflect a decrease in the nitric oxide synthase activity, and concomitantly in reduced nitric oxide levels. Since glutamate and nitric oxide are closely linked in pathways associated with long-term potentiation (Bliss and Collingridge, 1993;Lynch, 2004). Since long-term potentiation is assumed to represent a physiological model for learning and memory (Lynch, 2004), this might be a potential mechanism underlying cognitive deficits in a TRP deficiency model.…”

“…Since glutamate and nitric oxide are closely linked in pathways associated with long-term potentiation (Bliss and Collingridge, 1993;Lynch, 2004). Since long-term potentiation is assumed to represent a physiological model for learning and memory (Lynch, 2004), this might be a potential mechanism underlying cognitive deficits in a TRP deficiency model. As mentioned earlier, 5-HT 6 antagonists seem to increase excitatory neurotransmission (Dawson et al, 2001).…”

Mechanism for long-term memory formation when synaptic strengthening is impaired

“…synaptic plasticity | hippocampus | immediate-early gene | reconsolidation A fundamental question in neuroscience concerns the cellular mechanisms that lead to long-term memory (LTM) formation (1)(2)(3). It has been shown that LTM formation is associated with and demands strengthening of existing synapses, socalled functional plasticity (3)(4)(5), but it may also be linked with a more overt form of structural plasticity, an increase in synapse density (6)(7)(8)(9).…”