DOCSLIB.ORG

Long-Term Potentiation: What’S Learning Got to Do with It?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Long-Term Potentiation: What’S Learning Got to Do with It? BEHAVIORAL AND BRAIN SCIENCES (1997) 20, 597±655 Printed in the United States of America Long-term potentiation: What's learning got to do with it? Tracey J. Shors Department of Psychology and Program in Neuroscience, Princeton University, Princeton, NJ 08544 Electronic mail: shors࠾princeton.edu Louis D. Matzel Department of Psychology, Program in Biopsychology and Behavioral Neuroscience, Rutgers University, New Brunswick, NJ 08903 Electronic mail: matzel࠾rci.rutgers.edu 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 ªHebbianº 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. Keywords: arousal; attention; calcium; classical conditioning; Hebbian synapses; hippocampus; memory systems; NMDA; spatial learning; synaptic plasticity; theta rhythm 1. Introduction underestimates the research effort, insofar as many articles that address LTP do not use ªlong-term potentiationº in Few topics in neurobiology have attracted as much atten- the title or they refer to the same phenomenon by a tion or resources over the past 20 years as the phenomenon different name (e.g., ªlong-term enhancementº; Mc- of LTP (long-term potentiation), a putative mechanism for Naughton et al. 1986). the induction of stable memories in the mammalian brain. The concerted attention that LTP has attracted over time Long-term potentiation is typically expressed as an in- perhaps carries no surprise for those familiar with the crease in synaptic efficacy lasting from hours to days fol- search for the engram (a neural memory store) and the lowing brief tetanic (high-frequency) stimulation of an associated mechanism that could account for its formation. afferent pathway. [See Vanderwolf & Robinson's ªReticulo- Prior to the observation of LTP, the search had produced Cortical Activity and Behavior. BBS 4(3) 1981.] Thus, fol- virtually no viable candidate mechanisms, at least for the lowing LTP induction, a fixed amount of presynaptic stim- vertebrate nervous system (cf. Kandel & Tauc 1965a; ulation induces a ªpotentiatedº postsynaptic response, for 1965b). In this regard, LTP has been and still may be the example, an increase in EPSPs (excitatory post-synaptic best candidate. In several recent reviews, various authors potentials). The phenomenon of LTP was initially observed have concluded not only that LTP is a viable mechanism for in 1966 by Terje Lomo, then working in the laboratory of the induction and storage of memories but that it is the Per Andersen. In 1973, the first full article described LTP most promising candidate (e.g., Morris et al. 1991). In one in the hippocampus of the rabbit, a collaborative effort article (Martinez & Derrick 1996), the authors review between Lomo and Timothy Bliss (see also Bliss & Gard- recent evidence suggesting that the link between LTP and ner-Medwin 1973). By 1989, the U.S. National Library of memory is in some cases tenuous, and in others even Medicine listed some 312 articles with the term ªlong-term contradictory. Nevertheless, they conclude that ªmost evi- potentiationº in the title, and, in the 1990s alone, over dence firmly supports a role for LTP in learning and 1,000 additional articles have appeared. This search vastly memoryº (see also Eichenbaum & Otto 1993). This conclu- ᮊ 1997 Cambridge University Press 0140-525X/XX $9.00ϩ.10 597 Shors & Matzel: Long-term potentiation sion is based, in part, on a commonly echoed assertion that, (1973), in the CA3 pyramidal cells by stimulation of the although no direct evidence links LTP to memory, no better mossy fibers (see, e.g., Alger & Teyler 1976; Yamamoto & mechanism has been postulated. This assertion is encom- Chujo 1978), and in the CA1 pyramidal cells by stimulation passed by the broader argument that a good theory should of the Schaffer collateral branches of the CA3 neurons not be abandoned until a better one replaces it, an approach (Andersen et al. 1977; Schwartzkroin & Wester 1975). The with obvious merit. On the other hand, explicit confidence initial description of LTP in the hippocampus was probably in the validity of a prevailing theory can interfere with the fortuitous for memory research; had LTP first been identi- development of viable alternatives and new approaches to a fied in a brain region with less of a historical link to memory problem. Einstein once stated that ªit is the theory which formation (see, e.g., Olds 1955; Scoville & Milner 1957), it decides what we can observeº (see also Kuhn 1973). A might not have received such focused attention. Since flawed theory, the explanatory value of which is outweighed 1973, however, LTP has been found to occur in many brain by the inconsistencies that it introduces, can serve only as a regions, including the piriform (Stripling et al. 1988), ento- detriment to empirical progress. To the extent that a theory rhinal (Wilhite et al. 1986), and prefrontal (Laroche et al. is maintained by popular consensus, ªwhat we can observeº 1989) cortices, the septum (Racine et al. 1983), the auto- will necessarily be obscured by the convictions that a nomic (Libet et al. 1975) and superior (Brown & McAfee theory's advocates embrace. 1982) cervical ganglia, and the ventral horn of the spinal Given the vast amount of attention that LTP has gener- cord (Pockett & Figurov 1993). Furthermore, LTP is not ated over the past 20 years, it seems an appropriate time to limited to the mammalian brain but has been described in review the cellular and behavioral characteristics of LTP other vertebrates as well, such as the goldfish (Lewis & that led us to consider it as a memory device in the first Teyler 1986; Yang et al. 1990), bullfrog (Koyano et al. 1985), place. We should evaluate whether these properties remain bird (Scott & Bennett 1993), and lizard (Larson & Lynch viable features of a memory device and, if so, whether LTP 1985) and also in some invertebrates (Glanzman 1995; remains the most viable mechanism to serve that broader Walters & Byrne 1985). Because negative findings are function. Of particular concern here is a distinction that we usually not definitive, it cannot be said with certainty that will draw between LTP and the formation and storage of LTP cannot be induced in a particular brain region, but it is memories versus a link between LTP and the processes that safe to say that phenomena fitting the general description of ªinfluenceº the formation and storage of memories. By LTP occur ubiquitously throughout the nervous system. If ªinfluence,º we mean that LTP may be neither a necessary LTP is a ubiquitous feature of the nervous system, what nor a sufficient condition for the actual storage of memo- might that mean with respect to its potential role in learning ries, but LTP or an endogenous equivalent could act to and memory? Moreover, if LTP is indeed a learning and facilitate and maintain learning indirectly by altering the memory device, what would such a wide distribution tell us organism's responsiveness to, or perception of, environ- about the neural mechanisms of memory formation? mental stimuli. In this target article, we first review a Most researchers would agree that memory formation number of the cellular properties intrinsic to LTP, with a requires, or at least utilizes, wide and distributed brain particular emphasis on hippocampal LTP and the charac- regions, and the hippocampus is clearly not the only ªstor- teristics most commonly presented as evidence for its ageº site for memory; humans and infrahumans do not relationship to memory. It is important to stress that, even if require a hippocampus to acquire many forms of memory, hippocampal LTP was the ªlearning mechanism,º we would and, even in tasks dependent on the hippocampus for not expect individual synapses to express characteristics of acquisition, the structure is typically not required for later learning and memory processes. Nevertheless, we discuss retrieval. If we begin with the premise that many memories them because they are the features commonly cited as are not actually stored in the hippocampus, then what evidence for the role of LTP in learning, and this will allow function might LTP serve there? Before discussing the role us to evaluate the overall consistency of the evidence of LTP in memory or any behavioral processes, however, we supporting LTP as a mechanism of memory storage.
Load more

Recommended publications
  • Long-Term Potentiation Differentially Affects Two Components of Synaptic
    Proc. Nati. Acad. Sci. USA Vol. 85, pp. 9346-9350, December 1988 Neurobiology Long-term potentiation differentially affects two components of synaptic responses in hippocampus (plasticity/N-methyl-D-aspartate/D-2-amino-5-phosphonovglerate/facilitation) DOMINIQUE MULLER*t AND GARY LYNCH Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA 92717 Communicated by Leon N Cooper, September 6, 1988 (receivedfor review June 20, 1988) ABSTRACT We have used low magnesium concentrations ing electrode was positioned in field CAlb between two and the specific antagonist D-2-amino-5-phosphonopentanoate stimulating electrodes placed in fields CAla and CAlc; this (D-AP5) to estimate the effects of long-term potentiation (LTP) allowed us to activate separate inputs to a common pool of on the N-methyl-D-aspartate (NMDA) and non-NMDA recep- target cells. Stimulation voltages were adjusted to produce tor-mediated components of postsynaptic responses. LTP in- field EPSPs of -1.5 mV and did not elicit population spikes duction resulted in a considerably larger potentiation of non- in any of the responses included for data analysis. NMDA as opposed to NMDA receptor-related currents. In- Paired-pulse facilitation was produced by applying two creasing the size of postsynaptic potentials with greater stimulation pulses separated by 30 or 50 ms to the same stimulation currents or with paired-pulse facilitation produced stimulating electrode and LTP was induced by patterned opposite effects; i.e., those aspects ofthe response dependent on burst stimulation-i.e., 10 bursts delivered at 5 Hz, each NMDA receptor's increased to a greater degree than did those burst being composed of four pulses at 100 Hz (see ref.
    [Show full text]
  • Neuromodulators and Long-Term Synaptic Plasticity in Learning and Memory: a Steered-Glutamatergic Perspective
    brain sciences Review Neuromodulators and Long-Term Synaptic Plasticity in Learning and Memory: A Steered-Glutamatergic Perspective Amjad H. Bazzari * and H. Rheinallt Parri School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK; [email protected] * Correspondence: [email protected]; Tel.: +44-(0)1212044186 Received: 7 October 2019; Accepted: 29 October 2019; Published: 31 October 2019 Abstract: The molecular pathways underlying the induction and maintenance of long-term synaptic plasticity have been extensively investigated revealing various mechanisms by which neurons control their synaptic strength. The dynamic nature of neuronal connections combined with plasticity-mediated long-lasting structural and functional alterations provide valuable insights into neuronal encoding processes as molecular substrates of not only learning and memory but potentially other sensory, motor and behavioural functions that reflect previous experience. However, one key element receiving little attention in the study of synaptic plasticity is the role of neuromodulators, which are known to orchestrate neuronal activity on brain-wide, network and synaptic scales. We aim to review current evidence on the mechanisms by which certain modulators, namely dopamine, acetylcholine, noradrenaline and serotonin, control synaptic plasticity induction through corresponding metabotropic receptors in a pathway-specific manner. Lastly, we propose that neuromodulators control plasticity outcomes through steering glutamatergic transmission, thereby gating its induction and maintenance. Keywords: neuromodulators; synaptic plasticity; learning; memory; LTP; LTD; GPCR; astrocytes 1. Introduction A huge emphasis has been put into discovering the molecular pathways that govern synaptic plasticity induction since it was first discovered [1], which markedly improved our understanding of the functional aspects of plasticity while introducing a surprisingly tremendous complexity due to numerous mechanisms involved despite sharing common “glutamatergic” mediators [2].
    [Show full text]
  • Neurophysiology of Frog Dorsal Root Afferent Fibers and Their Intraspinal Processes
    Loyola University Chicago Loyola eCommons Dissertations Theses and Dissertations 1989 Neurophysiology of Frog Dorsal Root Afferent Fibers and Their Intraspinal Processes Nancy C. Tkacs Loyola University Chicago Follow this and additional works at: https://ecommons.luc.edu/luc_diss Part of the Physiology Commons Recommended Citation Tkacs, Nancy C., "Neurophysiology of Frog Dorsal Root Afferent Fibers and Their Intraspinal Processes" (1989). Dissertations. 2652. https://ecommons.luc.edu/luc_diss/2652 This Dissertation is brought to you for free and open access by the Theses and Dissertations at Loyola eCommons. It has been accepted for inclusion in Dissertations by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. Copyright © 1989 Nancy C. Tkacs UBRA~Y·· NEUROPHYSIOLOGY OF FROG DORSAL ROOT AFFERENT FIBERS AND THEIR INTRASPINAL PROCESSES by Nancy C. Tkacs A Dissertation Submitted to the Faculty of the Graduate School of .Loyola University of Chicago in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy April 1989 DEDICATION To Bill, with deep love and gratitude ii ACKNOWLEDG.EMENTS I would like to thank the faculty of the Department of Physiology for the excellent training I have received. I am particularly grateful to Dr. James Filkins for supporting my dissertation research. My thanks also go to Dr. Charles Webber, Dr. David Euler, Dr. David Carpenter, and Dr. Sarah Shefner for serving on my dissertation committee. Their helpful suggestions added much to the research and the dissertation. My gratitude goes to several individuals who unselfishly shared their time, resources, and expertise.
    [Show full text]
  • Action Potential and Synapses
    SENSORY RECEPTORS RECEPTORS GATEWAY TO THE PERCEPTION AND SENSATION Registering of inputs, coding, integration and adequate response PROPERTIES OF THE SENSORY SYSTEM According the type of the stimulus: According to function: MECHANORECEPTORS Telereceptors CHEMORECEPTORS Exteroreceptors THERMORECEPTORS Proprioreceptors PHOTORECEPTORS interoreceptors NOCICEPTORS STIMULUS Reception Receptor – modified nerve or epithelial cell responsive to changes in external or internal environment with the ability to code these changes as electrical potentials Adequate stimulus – stimulus to which the receptor has lowest threshold – maximum sensitivity Transduction – transformation of the stimulus to membrane potential – to generator potential– to action potential Transmission – stimulus energies are transported to CNS in the form of action potentials Integration – sensory information is transported to CNS as frequency code (quantity of the stimulus, quantity of environmental changes) •Sensation is the awareness of changes in the internal and external environment •Perception is the conscious interpretation of those stimuli CLASSIFICATION OF RECEPTORS - adaptation NONADAPTING RECEPTORS WITH CONSTANT FIRING BY CONSTANT STIMULUS NONADAPTING – PAIN TONIC – SLOWLY ADAPTING With decrease of firing (AP frequency) by constant stimulus PHASIC– RAPIDLY ADAPTING With rapid decrease of firing (AP frequency) by constant stimulus ACCOMODATION – ADAPTATION CHARACTERISTICS OF PHASIC RECEPTORS ALTERATIONS OF THE MEMBRANE POTENTIAL ACTION POTENTIAL TRANSMEMBRANE POTENTIAL
    [Show full text]
  • Fast and Slow Synaptic Potentials Produced Ina Mammalian
    Proc. Nat!. Acad. Sci. USA Vol. 83, pp. 1941-1944, March 1986 Neurobiology Fast and slow synaptic potentials produced in a mammalian sympathetic ganglion by colon distension (visceral afferent/inferior mesenteric ganglion/noncholinergic) STEPHEN PETERS AND DAVID L. KREULEN Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, AZ 85724 Communicated by C. Ladd Prosser, November 1, 1985 ABSTRACT Radial distension of the large intestine pro- way also comprises noncholinergic fibers; indeed, it remains duced a slow depolarization in a population of neurons in the to be determined whether noncholinergic slow EPSPs even inferior mesenteric ganglion of the guinea pig. The slow occur physiologically. potentials often occurred simultaneously with cholinergic fast We report here the discovery of a noncholinergic sensory potentials [(excitatory postsynaptic potentials (EPSPs)] yet pathway that projects from the distal colon to the inferior persisted in the presence of nicotinic and muscarinic choliner- mesenteric ganglion (1MG) of the guinea pig. This pathway, gic antagonists when all fast EPSPs were absent. The amplitude activated by colon distension, produces noncholinergic slow of the distension-induced noncholinergic slow depolarization depolarizations resembling nerve-evoked slow EPSPs in increased with increasing distension pressure. For distensions sympathetic ganglion cells. Often, distension of the colon of 1-min duration at pressures of 10-20 cm of water, the mean produced both an increase in cholinergic EPSPs and a slow depolarization amplitude was 3.4 mV. The slow depolarization depolarization, suggesting a simultaneous action of two was associated with an increase in membrane resistance, and cell. The prolonged periods ofcolon distension resulted in a tachyphylax- different neurotransmitters on a single ganglion is of the depolarization.
    [Show full text]
  • Neural Plasticity in the Brain During Neuropathic Pain
    biomedicines Review Neural Plasticity in the Brain during Neuropathic Pain Myeong Seong Bak 1, Haney Park 1 and Sun Kwang Kim 1,2,* 1 Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea; [email protected] (M.S.B.); [email protected] (H.P.) 2 Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea * Correspondence: [email protected]; Tel.: +82-2-961-0491 Abstract: Neuropathic pain is an intractable chronic pain, caused by damage to the somatosensory nervous system. To date, treatment for neuropathic pain has limited effects. For the development of efficient therapeutic methods, it is essential to fully understand the pathological mechanisms of neuropathic pain. Besides abnormal sensitization in the periphery and spinal cord, accumulating evidence suggests that neural plasticity in the brain is also critical for the development and mainte- nance of this pain. Recent technological advances in the measurement and manipulation of neuronal activity allow us to understand maladaptive plastic changes in the brain during neuropathic pain more precisely and modulate brain activity to reverse pain states at the preclinical and clinical levels. In this review paper, we discuss the current understanding of pathological neural plasticity in the four pain-related brain areas: the primary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray, and the basal ganglia. We also discuss potential treatments for neuropathic pain based on the modulation of neural plasticity in these brain areas. Keywords: neuropathic pain; neural plasticity; primary somatosensory cortex; anterior cingulate cortex; periaqueductal grey; basal ganglia Citation: Bak, M.S.; Park, H.; Kim, S.K.
    [Show full text]
  • Nervous Tissue
    Nervous Tissue • Controls and integrates all body activities within limits that maintain life • Three basic functions – sensing changes with sensory receptors • fullness of stomach or sun on your face – interpreting and remembering those changes – reacting to those changes with effectors • muscular contractions • glandular secretions 12-1 Major Structures of the Nervous System • Brain, cranial nerves, spinal cord, spinal nerves, ganglia, enteric plexuses and sensory receptors 12-2 Organization of the Nervous System • CNS is brain and spinal cord • PNS is everything else 12-3 Nervous System Divisions • Central nervous system (CNS) – consists of the brain and spinal cord • Peripheral nervous system (PNS) – consists of cranial and spinal nerves that contain both sensory and motor fibers – connects CNS to muscles, glands & all sensory receptors 12-4 Subdivisions of the PNS • Somatic (voluntary) nervous system (SNS) – neurons from cutaneous and special sensory receptors to the CNS – motor neurons to skeletal muscle tissue • Autonomic (involuntary) nervous systems – sensory neurons from visceral organs to CNS – motor neurons to smooth & cardiac muscle and glands • sympathetic division (speeds up heart rate) • parasympathetic division (slow down heart rate) • Enteric nervous system (ENS) – involuntary sensory & motor neurons control GI tract – neurons function independently of ANS & CNS 12-5 Neurons • Functional unit of nervous system • Have capacity to produce action potentials – electrical excitability • Cell body • Cell processes = dendrites
    [Show full text]
  • Bi 360 Week 4 Discussion Questions: Electrical and Chemical Synapses
    Bi 360 Week 4 Discussion Questions: Electrical and Chemical Synapses 1a) What is the difference between a non-rectifying electrical synapse and a rectifying electrical synapse? A non-rectifying electrical synapse allows information to flow between two cells in either direction (presynaptic cell postsynaptic cell and postsynaptic cell presynaptic cell). A rectifying electrical synapse allows information to flow in only one direction; positive current will flow in one direction which is equivalent to negative current flowing in the opposite direction. 1b) You are conducting a voltage clamp experiment to determine the properties of a synapse within the central nervous system. You conduct the experiment as follows: 1) You depolarize the presynaptic cell and record the voltage in both the pre- and the postsynaptic cell. 2) You hyperpolarize the presynaptic cell and record from the pre- and postsynaptic cell. 3) You depolarize the postsynaptic cell and record from the pre- and postsynaptic cell. 4) You hyperpolarize the postsynaptic cell and record from the pre- and postsynaptic cell. Analyze each piece of data shown below and determine what kind of synapse this is. How did you draw your conclusion? This is a rectifying electrical synapse. When you depolarize the presynaptic cell, there is a response in both the pre and post synaptic cell. When the postsynaptic cell is depolarized, however, there is a depolarization in the postsynaptic cell but no response in the presynaptic cell. A similar trend can be seen in the hyperpolarizing data but in the opposite direction. This means there must be a voltage dependent gate allowing positive current to flow in one direction while preventing it from flowing in the other.
    [Show full text]
  • Intracellular Domains of NMDA Receptor Subtypes Are Determinants for Long-Term Potentiation Induction
    The Journal of Neuroscience, November 26, 2003 • 23(34):10791–10799 • 10791 Cellular/Molecular Intracellular Domains of NMDA Receptor Subtypes Are Determinants for Long-Term Potentiation Induction Georg Ko¨hr,1 Vidar Jensen,3 Helmut J. Koester,2 Andre L. A. Mihaljevic,1 Jo K. Utvik,4 Ane Kvello,3 Ole P. Ottersen,4 Peter H. Seeburg,1 Rolf Sprengel,1 and Øivind Hvalby3 1Max-Planck-Institute for Medical Research, D-69120 Heidelberg, Germany, 2Baylor College of Medicine, Houston, Texas 77030, and 3Institute of Basic Medical Sciences and 4Centre for Molecular Biology and Neuroscience and Department of Anatomy, University of Oslo, N-0317 Oslo, Norway NMDA receptors (NMDARs) are essential for modulating synaptic strength at central synapses. At hippocampal CA3-to-CA1 synapses of adult mice, different NMDAR subtypes with distinct functionality assemble from NR1 with NR2A and/or NR2B subunits. Here we investigated the role of these NMDA receptor subtypes in long-term potentiation (LTP) induction. Because of the higher NR2B contri- bution in the young hippocampus, LTP of extracellular field potentials could be enhanced by repeated tetanic stimulation in young but not in adult mice. Similarly, NR2B-specific antagonists reduced LTP in young but only marginally in adult wild-type mice, further demonstrating that in mature CA3-to-CA1 connections LTP induction results primarily from NR2A-type signaling. This finding is also supported by gene-targeted mutant mice expressing C-terminally truncated NR2A subunits, which participate in synaptic NMDAR ϩ channel formation and Ca 2 signaling, as indicated by immunopurified synaptic receptors, postembedding immunogold labeling, and ϩ spinous Ca 2 transients in the presence of NR2B blockers.
    [Show full text]
  • LTP, STP, and Scaling: Electrophysiological, Biochemical, and Structural Mechanisms
    This position paper has not been peer reviewed or edited. It will be finalized, reviewed and edited after the Royal Society meeting on ‘Integrating Hebbian and homeostatic plasticity’ (April 2016). LTP, STP, and scaling: electrophysiological, biochemical, and structural mechanisms John Lisman, Dept. Biology, Brandeis University, Waltham Ma. [email protected] ABSTRACT: Synapses are complex because they perform multiple functions, including at least six mechanistically different forms of plasticity (STP, early LTP, late LTP, LTD, distance‐dependent scaling, and homeostatic scaling). The ultimate goal of neuroscience is to provide an electrophysiologically, biochemically, and structurally specific explanation of the underlying mechanisms. This review summarizes the still limited progress towards this goal. Several areas of particular progress will be highlighted: 1) STP, a Hebbian process that requires small amounts of synaptic input, appears to make strong contributions to some forms of working memory. 2) The rules for LTP induction in the stratum radiatum of the hippocampus have been clarified: induction does not depend obligatorily on backpropagating Na spikes but, rather, on dendritic branch‐specific NMDA spikes. Thus, computational models based on STDP need to be modified. 3) Late LTP, a process that requires a dopamine signal (neoHebbian), is mediated by trans‐ synaptic growth of the synapse, a growth that occurs about an hour after LTP induction. 4) There is no firm evidence for cell‐autonomous homeostatic synaptic scaling; rather, homeostasis is likely to depend on a) cell‐autonomous processes that are not scaling, b) synaptic scaling that is not cell autonomous but instead depends on population activity, or c) metaplasticity processes that change the propensity of LTP vs LTD.
    [Show full text]
  • Front Matter (PDF)
    When moving ahead means not momng at all. When you're probing or recording at Because accidents hap- the single-cell level, there's no room for pen, our exclusive CleanTop error, or vibration. surface design safely con- That's why leading researchers world- tains spills of water and other wide specify TMC vibration corrosive liquids. And it also isolation systems: laboratory maintains the highest level of structural damping and The 1-inch long welded tables, optical tables, and steel cups in our patented table-top and floor platforms. stiffness needed for the most CleanTop honeycomb top Our patented Gimbal Piston ®Air critical applications, safely contain spills. Isolator System effectively eliminates So when you absolutely need to move ahead, both vertical and horizontal floor vibra- move up to TMC, the world's most intelligent Ouroil-free Gimbal tion. When it's combined with our vibration solution. Contact our Technical Sales Piston provides isolation unique, highly damped, stainless steel in all directions, for even Group today. I the lowest input levels, laminate top or all-steel, spillproof CleanTop,~ iM you are assured of unequalled Technical Manufacturing Corporatlon 15 Centennial Drive • Peabody, MA 01960, USA performance, guaranteed. Our stainless steel laminated top is ideal Tel: 508-532-6330 • 800-542-9725 Fax: 508-531-8682 if mounting holes are not required. Vibmlion Solutions NG Editors Ronald Davis (Houston) Richard Morris (Edinburgh) Larry Squire (San Diego) Eric Kandel (New York) Carla Shatz (Berkeley) Charles Stevens (La Jolla) Managing Editor Judy Cuddihy (Cold Spring Harbor) Editorial Board Per Anderson (Oslo) Martin Heisenberg (Wurzburg) Philippe Ascher (Paris) Susan Hockfleld (New Haven) Man D.
    [Show full text]
  • Press Release
    PRESS RELEASE STRICTLY EMBARGOED UNTIL 14.00 GMT 1 MARCH 2016 Ground-breaking research into memory honoured with the world’s largest prize for brain research Three British neuroscientists have today (1 March) won the world’s most valuable prize for brain research, for their outstanding work on the mechanisms of memory. This year’s winners of The Brain Prize are Tim Bliss, Graham Collingridge and Richard Morris. The Brain Prize, awarded by the Grete Lundbeck European Brain Research Foundation in Denmark is worth one million Euros. Awarded annually, it recognises one or more scientists who have distinguished themselves by an outstanding contribution to neuroscience. The research by Professors Bliss, Collingridge and Morris has focused on a brain mechanism known as ‘Long-Term Potentiation’ (LTP), which underpins the life-long plasticity of the brain. Their discoveries have revolutionised our understanding of how memories are formed, retained and lost. The three neuroscientists have independently and collectively shown how the connections – the synapses - between brain cells in the hippocampus (a structure vital for the formation of new memories) can be strengthened through repeated stimulation. LTP is so-called because it can persist indefinitely. Their work has revealed some of the basic mechanisms behind the phenomenon and has shown that LTP is the basis for our ability to learn and remember. Sir Colin Blakemore, chairman of the selection committee said “Memory is at the heart of humanexperience. This year’s winners, through their ground-breaking research, have transformed our understanding of memory and learning, and the devastating effects of failing memory.” Without the capacity to store information in our brains, we could not remember our past and would be incapable of planning our future.
    [Show full text]