DOCSLIB.ORG

"Long-Term Potentiation"

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Long-term Potentiation Advanced article Article Contents John Lisman, Brandeis University, Massachusetts, USA . Introduction . Synapse Specificity and Associative Nature of Long-term Long-term potentiation is an activity-dependent strengthening of synapses that is Potentiation thought to underlie memory. Long-term Potentiation as a Mechanism for Memory Storage . Role of Calcium Entry through NMDA Receptor Channels . Presynaptic versus Postsynaptic Sites for Expression of Introduction Long-term Potentiation . Molecular Mechanisms of Long-term Potentiation One of the major unsolved problems in neuroscience is . Structural Modification of Synapses and Changes in Gene the mechanism by which memory is stored in the brain. Expression Some property of our neurons must change when we . Prospects learn, but what parts of the neuron change and the mo- lecular basis of these changes is not known. Long-term doi: 10.1002/9780470015902.a0000165.pub2 potentiation (LTP) has been a focus of efforts to under- stand memory. The term refers to a long-lasting strength- ening of synapses that can be triggered by particular brief patterns of synaptic stimulation. Other patterns can pro- Synapse Specificity and Associative duce a long-term weakening of synapses; this result is termed as long-term depression (LTD) or depotentiation. Nature of Long-term Potentiation These findings show that synapses have a defined strength and that this strength can be bidirectionally There are two properties of LTP that have made it a par- modified. The evidence that such changes in synaptic ticularly attractive candidate for memory storage. The first strength are actually involved in memory has strength- is the finding that synapses can be independently modified. ened in recent years. One class of experiments involved The evidence for this ‘synapse specificity’ comes from ex- the selective genetic removal of N-methyl-D-aspartate periments in which two sets of synapses on to the same (NMDA) receptor channels from CA1 cells (Tsien et al., neuron are stimulated. If a tetanus is given to one set, these 1996). These mice lack the ability to induce LTP. synapses will be strengthened, but the synapses in the other Behavioural studies showed that the animals are defec- set will not. A more recent experiment used two-photon tive in learning and memory tasks. In a complementary uncaging of glutamate in the direct vicinity of an individual approach, two groups of experimenters (Gruart et al., synapse (Matsuzaki et al., 2004). Such stimulation could be 2006; Whitlock et al., 2006) have demonstrated the con- used to induce LTP at that synapse in much the way LTP is verse correlation, namely that learning tasks induce LTP induced by presynaptically released glutamate. The re- in CA1 cells. markable finding was that other nonstimulated synapses Several fundamentally different forms of LTP have only microns away did not undergo LTP. These results been discovered. This article will focus on the most stud- indicate that each synapse can be used to store information. ied form that found at the glutamatergic synapses of the Because most neurons have over 10 000 excitatory CA1 region of the hippocampus. A typical experiment synapses, the potential for information storage is vast. starts by measuring the strength of a group of synapses. See also: Neurons This is done by firing a single action potential in some of The second attractive property of LTP is that it is asso- the axons that enter this region. These axons make ciative. According to nerve network theory (see next sec- synapses with pyramidal cells and generate a graded ex- tion), it is this property that enables small changes in many citatory postsynaptic potential (EPSP). The strength of synapses to produce distributed storage of a complex the synapses is defined by the magnitude of the EPSP. memory in a nerve network. What associativity means is LTP is then induced by stimulating the axons to fire at that LTP cannot be triggered by activity in a single input high frequency (typically 100 Hz for 1 s), a stimulus re- axon, but can be triggered if that activity is associated with ferred to as a tetanus. The remarkable finding is that this other active excitatory inputs. The basis of this ass- brief tetanus causes a long-lasting potentiation of the ociativity requirement is that LTP induction requires the strength of the synapses. The size of the EPSP typically membrane voltage of the pyramidal cell to become very increases by 50–100% but can increase by as much as depolarized (a positive deflection from resting potential) by 800%. In the brain-slice preparation used for most stud- an amount much larger than that produced by a single ies, potentiation persists until the slice is no longer viable excitatory synaptic input (500 mV). This requirement has (5–12 h). LTP can also be induced in living animals, and been demonstrated by artificially depolarizing the cell with there it can persist for at least a year. positive current. Under these conditions, even stimulation ENCYCLOPEDIA OF LIFE SCIENCES & 2007, John Wiley & Sons, Ltd. www.els.net 1 Long-term Potentiation of a single input can produce LTP. Conversely, if many Role of Calcium Entry through NMDA inputs are stimulated, but the cell is hyperpolarized (made more negative) by current injection, LTP does not occur. Receptor Channels Thus, a synapse will be strengthened if two conditions are met: the synapse is activated by presynaptic activity and A major discovery is that the properties of a single receptor, there is substantial postsynaptic depolarization due to the NMDA receptor, can account for the Hebbian prop- other excitatory inputs (and not too much inhibitory in- erty of LTP. The NMDA receptor channel is one of the two put). This dual requirement for strengthening is often re- major subtypes of ionotropic receptors for the neurotrans- ferred to as the ‘Hebb rule’. See also: Membrane Potential mitter glutamate, the neurotransmitter at most excitatory One of the elegant aspects of the Hebb rule is that it can synapses in the central nervous system. The other major be executed at each synapse using information that is lo- subtype of ionotropic receptor is the a-amino-3-hydroxy- cally available. A synapse can ‘know’ that its presynaptic 5-methyl-4-isoxazolepropionate (AMPA) receptor. These input is active because its receptors will be activated by the receptors are also ion channels and they produce the bulk neurotransmitter released. The synapse can also ‘know’ of the excitatory postsynaptic potential. The function of about the overall depolarization of the neuron because NMDA receptors was unclear until it was shown that they this spreads fairly uniformly over the cell membrane; to a have a special role in synaptic plasticity. This was demon- first approximation, the voltage at any point reflects the strated by showing that if NMDA receptor channels are combined influence of all the excitatory and inhibitory in- pharmacologically blocked, LTP cannot be induced (Bliss puts on to a cell. Membrane ion channels in the postsy- and Collingridge, 1993). Subsequent work used genetic naptic membrane have the capability of sensing this methods to eliminate the NMDA receptor channel came to voltage. As we will see later, an ion channel called the the same conclusion. See also: Glutamate as a Neuro- (NMDA) receptor can in fact execute the Hebb rule by transmitter; NMDA Receptors sensing both presynaptic glutamate release and membrane An unusual property of NMDA receptor channels ex- depolarization. plains how these channels trigger LTP in accord with the Hebb rule. Most transmitter-activated channels are opened by transmitter alone; their opening does not depend on membrane voltage. In contrast, NMDA receptor channels Long-term Potentiation as a open only if there is also substantial postsynaptic depo- Mechanism for Memory Storage larization. This voltage dependence has a simple mecha- nism. If the postsynaptic neuron is near resting potential, The theory of nerve networks provides us with a rough glutamate cannot activate the channel because the pore of outline of how synapses in a network of neurons might the channel is blocked by external magnesium. However, if store a memory in a distributed way using a Hebbian form the postsynaptic neuron is depolarized, Mg2+ is electrically of LTP. Let us consider how a visual scene might be stored. driven out of the pore, and the channel can open. These The scene would first be processed by low-level networks in dual requirements for opening the NMDA receptor chan- which neurons responded to elementary visual features. nel are exactly the requirements for synaptic modification These features would then be synaptically associated in a according to the Hebb rule. See also: Neural Activity and higher-level network specialized for memory storage. In an the Development of Brain Circuits idealized version of such a memory network, each neuron But what is it about the opening of the NMDA receptor makes a synaptic connection with every other neuron and it channels that leads to LTP induction? It is now clear that is at these ‘recurrent’ connections that memory can be NMDA receptor channels are much more permeable to stored by the Hebbian modification. Let us say that when Ca2+ than are most AMPA receptor channels and that it is the visual scene is present, a subset of cells in the memory the influx of Ca2+ through the NMDA receptors that trig- network will fire, specifically cell x and a group of other gers LTP. A key finding was that LTP could be blocked by cells, G. Focusing on the connection of the G cells to the x intracellular Ca2+ buffers (Lynch et al., 1983), molecules cell, we can see that the Hebb rule will be satisfied at all that bind Ca2+ and prevent elevations in Ca2+ concentra- these synapses because there is both presynaptic input and tion.
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]
  • 11 Introduction to the Nervous System and Nervous Tissue
    11 Introduction to the Nervous System and Nervous Tissue ou can’t turn on the television or radio, much less go online, without seeing some- 11.1 Overview of the Nervous thing to remind you of the nervous system. From advertisements for medications System 381 Yto treat depression and other psychiatric conditions to stories about celebrities and 11.2 Nervous Tissue 384 their battles with illegal drugs, information about the nervous system is everywhere in 11.3 Electrophysiology our popular culture. And there is good reason for this—the nervous system controls our of Neurons 393 perception and experience of the world. In addition, it directs voluntary movement, and 11.4 Neuronal Synapses 406 is the seat of our consciousness, personality, and learning and memory. Along with the 11.5 Neurotransmitters 413 endocrine system, the nervous system regulates many aspects of homeostasis, including 11.6 Functional Groups respiratory rate, blood pressure, body temperature, the sleep/wake cycle, and blood pH. of Neurons 417 In this chapter we introduce the multitasking nervous system and its basic functions and divisions. We then examine the structure and physiology of the main tissue of the nervous system: nervous tissue. As you read, notice that many of the same principles you discovered in the muscle tissue chapter (see Chapter 10) apply here as well. MODULE 11.1 Overview of the Nervous System Learning Outcomes 1. Describe the major functions of the nervous system. 2. Describe the structures and basic functions of each organ of the central and peripheral nervous systems. 3. Explain the major differences between the two functional divisions of the peripheral nervous system.
    [Show full text]
  • A Dissertation Entitled the Induction of Traumatic Brain Injury by Blood
    A Dissertation entitled The Induction of Traumatic Brain Injury by Blood Brain Barrier Disruption by Mark D. Skopin Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Engineering ________________________________________________________ Dr. Scott C. Molitor, Ph.D., Committee Chair ________________________________________________________ Dr. Ragheb Assaly, M.D., Committee Member ________________________________________________________ Dr. Ronald L. Fournier, Ph.D., Committee Member ________________________________________________________ Dr. Hermann von Grafenstein, Ph.D., Committee Member ________________________________________________________ Dr. Patricia A. Relue, Ph.D., Committee Member ________________________________________________________ Dr. Patricia R. Komuniecki, Ph.D., Dean College of Graduate Studies The University of Toledo May 2011 Copyright 2011, Mark D. Skopin This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of The Induction of Traumatic Brain Injury by Blood Brain Barrier Disruption by Mark D. Skopin Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Engineering University of Toledo May 2011 Animal models of traumatic brain injury (TBI) are utilized for the study of underlying mechanisms and for the development of potential therapeutics. Traditional TBI models apply concussive
    [Show full text]
  • Evidence for Newly Generated Interneurons in the Basolateral Amygdala of Adult Mice
    OPEN Molecular Psychiatry (2018) 23, 521–532 www.nature.com/mp ORIGINAL ARTICLE Evidence for newly generated interneurons in the basolateral amygdala of adult mice DJ Jhaveri1,2,5, A Tedoldi1,5, S Hunt1, R Sullivan1, NR Watts3, JM Power4, PF Bartlett1,6 and P Sah1,6 New neurons are continually generated from the resident populations of precursor cells in selective niches of the adult mammalian brain such as the hippocampal dentate gyrus and the olfactory bulb. However, whether such cells are present in the adult amygdala, and their neurogenic capacity, is not known. Using the neurosphere assay, we demonstrate that a small number of precursor cells, the majority of which express Achaete-scute complex homolog 1 (Ascl1), are present in the basolateral amygdala (BLA) of the adult mouse. Using neuron-specific Thy1-YFP transgenic mice, we show that YFP+ cells in BLA-derived neurospheres have a neuronal morphology, co-express the neuronal marker βIII-tubulin, and generate action potentials, confirming their neuronal phenotype. In vivo, we demonstrate the presence of newly generated BrdU-labeled cells in the adult BLA, and show that a proportion of these cells co-express the immature neuronal marker doublecortin (DCX). Furthermore, we reveal that a significant proportion of GFP+ neurons (~23%) in the BLA are newly generated (BrdU+) in DCX-GFP mice, and using whole-cell recordings in acute slices we demonstrate that the GFP+ cells display electrophysiological properties that are characteristic of interneurons. Using retrovirus-GFP labeling as well as the Ascl1CreERT2 mouse line, we further confirm that the precursor cells within the BLA give rise to mature and functional interneurons that persist in the BLA for at least 8 weeks after their birth.
    [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]