The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses
02 Nov 2001-Science (American Association for the Advancement of Science)-Vol. 294, Iss: 5544, pp 1030-1038
TL;DR: This book aims to investigate elementary forms of learning and memory at a cellular molecular level—as specific molecular activities within identified nerve cells withinidentified nerve cells.
Abstract: One of the most remarkable aspects of an animal's behavior is the ability to modify that behavior by learning, an ability that reaches its highest form in human beings. For me, learning and memory have proven to be endlessly fascinating mental processes because they address one of the fundamental features of human activity: our ability to acquire new ideas from experience and to retain these ideas over time in memory. Moreover, unlike other mental processes such as thought, language, and consciousness, learning seemed from the outset to be readily accessible to cellular and molecular analysis. I, therefore, have been curious to know: What changes in the brain when we learn? And, once something is learned, how is that information retained in the brain? I have tried to address these questions through a reductionist approach that would allow me to investigate elementary forms of learning and memory at a cellular molecular level-as specific molecular activities within identified nerve cells.
Citations
More filters
TL;DR: Both the upstream components of the signaling pathway(s) that activates mammalian TOR (mTOR) and the downstream targets that affect protein synthesis are described.
Abstract: The evolutionarily conserved checkpoint protein kinase, TOR (target of rapamycin), has emerged as a major effector of cell growth and proliferation via the regulation of protein synthesis. Work in the last decade clearly demonstrates that TOR controls protein synthesis through a stunning number of downstream targets. Some of the targets are phosphorylated directly by TOR, but many are phosphorylated indirectly. In this review, we summarize some recent developments in this fast-evolving field. We describe both the upstream components of the signaling pathway(s) that activates mammalian TOR (mTOR) and the downstream targets that affect protein synthesis. We also summarize the roles of mTOR in the control of cell growth and proliferation, as well as its relevance to cancer and synaptic plasticity.
4,074 citations
Cites background from "The Molecular Biology of Memory Sto..."
...…see Mita et al. 2003; Sawyers 2003; Bjornsti and Houghton 2004; Houghton and Huang 2004). mTOR function in synaptic plasticity, memory, and learning The creation and maintenance of long-term memory requires new mRNA and protein synthesis (Kandel 2001), which are not required for short-term memory....
[...]
...The creation and maintenance of long-term memory requires new mRNA and protein synthesis (Kandel 2001), which are not required for short-term memory....
[...]
TL;DR: A role is demonstrated for BDNF and its val/met polymorphism in human memory and hippocampal function and it is suggested val/ met exerts these effects by impacting intracellular trafficking and activity-dependent secretion of BDNF.
3,599 citations
Cites background from "The Molecular Biology of Memory Sto..."
...A second stage, referred to as late Frederick, Maryland 21702 phase LTP (L-LTP), recruits the cAMP and CREB signal4 Section on Neural Development and Plasticity ing pathway to direct protein synthesis-dependent National Institute of Child Health and Human changes in structure andfunction of hippocampal synapses Development (Kandel, 2001)....
[...]
...…Maryland 21702 phase LTP (L-LTP), recruits the cAMP and CREB signal4 Section on Neural Development and Plasticity ing pathway to direct protein synthesis-dependent National Institute of Child Health and Human changes in structure andfunction of hippocampal synapses Development (Kandel, 2001)....
[...]
TL;DR: Dopamine release in the nucleus accumbens has been linked to the efficacy of these unconditioned rewards, but dopamine release in a broader range of structures is implicated in the 'stamping-in' of memory that attaches motivational importance to otherwise neutral environmental stimuli.
Abstract: The hypothesis that dopamine is important for reward has been proposed in a number of forms, each of which has been challenged. Normally, rewarding stimuli such as food, water, lateral hypothalamic brain stimulation and several drugs of abuse become ineffective as rewards in animals given performance-sparing doses of dopamine antagonists. Dopamine release in the nucleus accumbens has been linked to the efficacy of these unconditioned rewards, but dopamine release in a broader range of structures is implicated in the 'stamping-in' of memory that attaches motivational importance to otherwise neutral environmental stimuli.
3,012 citations
Cites background from "The Molecular Biology of Memory Sto..."
...In Aplysia californica , learning at the neuronal level has been demonstrated when a sensory neuron excites a motor neuron and that excitation occurs in the presence of the neuromodulatory transmitter serotoni...
[...]
TL;DR: This review focuses on the current level of understanding of where, when, and how CREB family members function in the nervous system.
1,984 citations
TL;DR: This review aims to comprehensively cover the field of "sleep and memory" research by providing a historical perspective on concepts and a discussion of more recent key findings.
Abstract: Over more than a century of research has established the fact that sleep benefits the retention of memory. In this review we aim to comprehensively cover the field of "sleep and memory" research by providing a historical perspective on concepts and a discussion of more recent key findings. Whereas initial theories posed a passive role for sleep enhancing memories by protecting them from interfering stimuli, current theories highlight an active role for sleep in which memories undergo a process of system consolidation during sleep. Whereas older research concentrated on the role of rapid-eye-movement (REM) sleep, recent work has revealed the importance of slow-wave sleep (SWS) for memory consolidation and also enlightened some of the underlying electrophysiological, neurochemical, and genetic mechanisms, as well as developmental aspects in these processes. Specifically, newer findings characterize sleep as a brain state optimizing memory consolidation, in opposition to the waking brain being optimized for encoding of memories. Consolidation originates from reactivation of recently encoded neuronal memory representations, which occur during SWS and transform respective representations for integration into long-term memory. Ensuing REM sleep may stabilize transformed memories. While elaborated with respect to hippocampus-dependent memories, the concept of an active redistribution of memory representations from networks serving as temporary store into long-term stores might hold also for non-hippocampus-dependent memory, and even for nonneuronal, i.e., immunological memories, giving rise to the idea that the offline consolidation of memory during sleep represents a principle of long-term memory formation established in quite different physiological systems.
1,964 citations
Cites background from "The Molecular Biology of Memory Sto..."
...Encoding induces synaptic long-term potentiation (LTP) or long-term depression (LTD) as major forms of learning-induced synaptic plasticity (222, 527, 616, 629, 1209)....
[...]
References
More filters
Book•
01 Jan 1978
TL;DR: The amnesic syndrome is presented as an extension of the theory to humans and the role of operators in the locale system is examined.
Abstract: Table of Contents: Chapter 1 - Remembrance of places past: a history of theories of space / Chapter 2 - Spatial behaviour / Chapter 3 - Anatomy / Chapter 4 - Physiology / Chapter 5 - Introduction to the lesion review / Chapter 6 - Exploration / Chapter 7 - Discrimination and maze learning / Chapter 8 - Aversively motivated behaviour / Chapter 9 - Operants: the limited role of the locale system / Chapter 10 - Reactions to reward change / Chapter 11 - Maintenance behaviours / Chapter 12 - Stimulation studies / Chapter 13 - Long-term memory / Chapter 14 - An extension of the theory to humans / Chapter 15 - The amnesic syndrome
8,313 citations
TL;DR: The after‐effects of repetitive stimulation of the perforant path fibres to the dentate area of the hippocampal formation have been examined with extracellular micro‐electrodes in rabbits anaesthetized with urethane.
Abstract: 1. The after-effects of repetitive stimulation of the perforant path fibres to the dentate area of the hippocampal formation have been examined with extracellular micro-electrodes in rabbits anaesthetized with urethane.2. In fifteen out of eighteen rabbits the population response recorded from granule cells in the dentate area to single perforant path volleys was potentiated for periods ranging from 30 min to 10 hr after one or more conditioning trains at 10-20/sec for 10-15 sec, or 100/sec for 3-4 sec.3. The population response was analysed in terms of three parameters: the amplitude of the population excitatory post-synaptic potential (e.p.s.p.), signalling the depolarization of the granule cells, and the amplitude and latency of the population spike, signalling the discharge of the granule cells.4. All three parameters were potentiated in 29% of the experiments; in other experiments in which long term changes occurred, potentiation was confined to one or two of the three parameters. A reduction in the latency of the population spike was the commonest sign of potentiation, occurring in 57% of all experiments. The amplitude of the population e.p.s.p. was increased in 43%, and of the population spike in 40%, of all experiments.5. During conditioning at 10-20/sec there was massive potentiation of the population spike (;frequency potentiation'). The spike was suppressed during stimulation at 100/sec. Both frequencies produced long-term potentiation.6. The results suggest that two independent mechanisms are responsible for long-lasting potentiation: (a) an increase in the efficiency of synaptic transmission at the perforant path synapses; (b) an increase in the excitability of the granule cell population.
7,008 citations
TL;DR: This article showed that chronic intraventricular infusion of D,L-AP5 causes a selective impairment of place learning, which is highly sensitive to hippocampal damage, without affecting visual discrimination learning.
Abstract: Recent work has shown that the hippocampus contains a class of receptors for the excitatory amino acid glutamate that are activated by N-methyl-D-aspartate (NMDA) and that exhibit a peculiar dependency on membrane voltage in becoming active only on depolarization. Blockade of these sites with the drug aminophosphonovaleric acid (AP5) does not detectably affect synaptic transmission in the hippocampus, but prevents the induction of hippocampal long-term potentiation (LTP) following brief high-frequency stimulation. We now report that chronic intraventricular infusion of D,L-AP5 causes a selective impairment of place learning, which is highly sensitive to hippocampal damage, without affecting visual discrimination learning, which is not. The L-isomer of AP5 did not produce behavioural effects. AP5 treatment also suppressed LTP in vivo. These results suggest that NMDA receptors are involved in spatial learning, and add support to the hypothesis that LTP is involved in some, but not all, forms of learning.
3,488 citations
TL;DR: The medial temporal lobe memory system is needed to bind together the distributed storage sites in neocortex that represent a whole memory, but the role of this system is only temporary, as time passes after learning, memory stored in neoc cortex gradually becomes independent of medialporal lobe structures.
Abstract: Studies of human amnesia and studies of an animal model of human amnesia in the monkey have identified the anatomical components of the brain system for memory in the medial temporal lobe and have illuminated its function. This neural system consists of the hippocampus and adjacent, anatomically related cortex, including entorhinal, perirhinal, and parahippocampal cortices. These structures, presumably by virtue of their widespread and reciprocal connections with neocortex, are essential for establishing long-term memory for facts and events (declarative memory). The medial temporal lobe memory system is needed to bind together the distributed storage sites in neocortex that represent a whole memory. However, the role of this system is only temporary. As time passes after learning, memory stored in neocortex gradually becomes independent of medial temporal lobe structures.
3,096 citations
Book•
01 Sep 1987
TL;DR: The first scientific text on the psychology of memory, Hermann Ebbinghaus extended the province of systematic, experimental research to the higher mental processes.
Abstract: The first scientific text on the psychology of memory. Relating retention to repetition, describing the shape of the forgetting curve, and measuring strength of association, Hermann Ebbinghaus extended the province of systematic, experimental research to the higher mental processes.
2,389 citations