Error message

No crossref credentials set for sci

Synaptic Theory of Working Memory

Science, 14 March 2008
Vol. 319, Issue 5869, p. 1543-1546
DOI: 10.1126/science.1150769

Synaptic Theory of Working Memory

  1. Gianluigi Mongillo1,*,,
  2. Omri Barak2,*,
  3. Misha Tsodyks2,§
  1. 1 Group for Neural Theory, Département d'Etudes Cognitives, Ecole Normale Supérieure et Collège-de-France, Paris, France.
  2. 2 Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
  1. § To whom correspondence should be addressed. E-mail: misha{at}
  • * These authors contributed equally to this work.

  • Present address: Laboratoire de Neurophysique et Physiologie, Université Paris-Descartes, CNRS-UMR8119, and Franco-Israeli Laboratory of System Neurophysiology and Neurophysics, Paris, France.

  • CNRS visiting member of the Group for Neural Theory, Ecole Normale Supérieure et Collège-de-France.


It is usually assumed that enhanced spiking activity in the form of persistent reverberation for several seconds is the neural correlate of working memory. Here, we propose that working memory is sustained by calcium-mediated synaptic facilitation in the recurrent connections of neocortical networks. In this account, the presynaptic residual calcium is used as a buffer that is loaded, refreshed, and read out by spiking activity. Because of the long time constants of calcium kinetics, the refresh rate can be low, resulting in a mechanism that is metabolically efficient and robust. The duration and stability of working memory can be regulated by modulating the spontaneous activity in the network.

    • Received for publication 20 September 2007.
    • Accepted for publication 21 January 2008.


    G. Mongillo, O. Barak, and M. Tsodyks, Synaptic Theory of Working Memory. Science 319, 1543-1546 (2008).

    Lateralized Delay Period Activity Marks the Focus of Spatial Attention in Working Memory: Evidence from Somatosensory Event-Related Brain Potentials
    T. Katus, and M. Eimer
    J. Neurosci. 35, 6689-6695 (29 April 2015)

    Spatiotemporal Memory Is an Intrinsic Property of Networks of Dissociated Cortical Neurons
    H. Ju, M. R. Dranias, G. Banumurthy, and A. M. J. VanDongen
    J. Neurosci. 35, 4040-4051 (4 March 2015)

    Differential Dynamics of Spatial Attention, Position, and Color Coding within the Parietofrontal Network
    E. Astrand, G. Ibos, J.-R. Duhamel, and S. Ben Hamed
    J. Neurosci. 35, 3174-3189 (18 February 2015)

    A model of order-selectivity based on dynamic changes in the balance of excitation and inhibition produced by short-term synaptic plasticity
    V. Goudar, and D. V. Buonomano
    J. Neurophysiol. 113, 509-523 (15 January 2015)

    Asymmetrical integration of sensory information during mating decisions in grasshoppers
    J. Clemens, S. Kramer, and B. Ronacher
    Proc. Natl. Acad. Sci. USA 111, 16562-16567 (18 November 2014)

    A Tradeoff Between Accuracy and Flexibility in a Working Memory Circuit Endowed with Slow Feedback Mechanisms
    J. Pereira, and X.-J. Wang
    Cereb Cortex 0, bhu202v1-bhu202 (24 September 2014)

    Differential cortical activation of the striatal direct and indirect pathway cells: reconciling the anatomical and optogenetic results by using a computational method
    K. Morita, and X.-J. Wang
    J. Neurophysiol. 112, 120-146 (1 July 2014)

    Frontal-Medial Temporal Interactions Mediate Transitions among Representational States in Short-Term Memory
    D. E. Nee, and J. Jonides
    J. Neurosci. 34, 7964-7975 (4 June 2014)

    Correspondence Between Stimulus Encoding- and Maintenance-Related Neural Processes Underlies Successful Working Memory
    J. R. Cohen, K. K. Sreenivasan, and M. D'Esposito
    Cereb Cortex 24, 593-599 (1 March 2014)

    The Cell-Type Specific Cortical Microcircuit: Relating Structure and Activity in a Full-Scale Spiking Network Model
    T. C. Potjans, and M. Diesmann
    Cereb Cortex 24, 785-806 (1 March 2014)

    Temporal structure in associative retrieval
    M. Diesmann
    elife 4, e04919-e04919 (1 January 2014)

    Causal Evidence for a Privileged Working Memory State in Early Visual Cortex
    N. Zokaei, S. Manohar, M. Husain, and E. Feredoes
    J. Neurosci. 34, 158-162 (1 January 2014)

    Short-term synaptic plasticity in the deterministic Tsodyks-Markram model leads to unpredictable network dynamics
    J. M. Cortes, M. Desroches, S. Rodrigues, R. Veltz, M. A. Munoz, and T. J. Sejnowski
    Proc. Natl. Acad. Sci. USA 110, 16610-16615 (8 October 2013)

    Synaptic Mechanisms Underlying Strong Reciprocal Connectivity between the Medial Prefrontal Cortex and Basolateral Amygdala
    J. P. Little, and A. G. Carter
    J. Neurosci. 33, 15333-15342 (25 September 2013)

    Selective visual processing across competition episodes: a theory of task-driven visual attention and working memory
    W. X. Schneider, and A. G. Carter
    Phil Trans R Soc B 368, 20130060-20130060 (9 September 2013)

    Theta Oscillations in the Medial Prefrontal Cortex Are Modulated by Spatial Working Memory and Synchronize with the Hippocampus through Its Ventral Subregion
    P.-K. O'Neill, J. A. Gordon, and T. Sigurdsson
    J. Neurosci. 33, 14211-14224 (28 August 2013)

    Control of layer 5 pyramidal cell spiking by oscillatory inhibition in the distal apical dendrites: a computational modeling study
    X. Li, K. Morita, H. P. C. Robinson, and M. Small
    J. Neurophysiol. 109, 2739-2756 (1 June 2013)

    Quantitative examination of stimulus-response relations in cortical networks in vitro
    O. Weihberger, S. Okujeni, J. E. Mikkonen, and U. Egert
    J. Neurophysiol. 109, 1764-1774 (1 April 2013)

    Short-Term Memory in Networks of Dissociated Cortical Neurons
    M. R. Dranias, H. Ju, E. Rajaram, and A. M. J. VanDongen
    J. Neurosci. 33, 1940-1953 (30 January 2013)

    Common Rules Guide Comparisons of Speed and Direction of Motion in the Dorsolateral Prefrontal Cortex
    C. R. Hussar, and T. Pasternak
    J. Neurosci. 33, 972-986 (16 January 2013)

    Short-Term Plasticity Explains Irregular Persistent Activity in Working Memory Tasks
    D. Hansel, and G. Mato
    J. Neurosci. 33, 133-149 (2 January 2013)

    Task-Relevant and Accessory Items in Working Memory Have Opposite Effects on Activity in Extrastriate Cortex
    J. C. Peters, P. R. Roelfsema, and R. Goebel
    J. Neurosci. 32, 17003-17011 (21 November 2012)

    Nonconserved Ca2+/Calmodulin Binding Sites in Munc13s Differentially Control Synaptic Short-Term Plasticity
    N. Lipstein, S. Schaks, K. Dimova, S. Kalkhof, C. Ihling, K. Kolbel, U. Ashery, J. Rhee, N. Brose, A. Sinz et al.
    Mol. Cell. Biol. 32, 4628-4641 (15 November 2012)

    Fundamental limits on persistent activity in networks of noisy neurons
    Y. Burak, and I. R. Fiete
    Proc. Natl. Acad. Sci. USA 109, 17645-17650 (23 October 2012)

    Dynamic afferent synapses to decision-making networks improve performance in tasks requiring stimulus associations and discriminations
    M. A. Bourjaily, and P. Miller
    J. Neurophysiol. 108, 513-527 (15 July 2012)

    Hyperconnectivity and Slow Synapses during Early Development of Medial Prefrontal Cortex in a Mouse Model for Mental Retardation and Autism
    G. Testa-Silva, A. Loebel, M. Giugliano, C. P. J. de Kock, H. D. Mansvelder, and R. M. Meredith
    Cereb Cortex 22, 1333-1342 (1 June 2012)

    Altered axonal targeting and short-term plasticity in the hippocampus of Disc1 mutant mice
    M. Kvajo, H. McKellar, L. J. Drew, A.-M. Lepagnol-Bestel, L. Xiao, R. J. Levy, R. Blazeski, P. A. Arguello, C. O. Lacefield, C. A. Mason et al.
    Proc. Natl. Acad. Sci. USA 108, E1349-E1358 (6 December 2011)

    Representation of comparison signals in cortical area MT during a delayed direction discrimination task
    L. L. Lui, and T. Pasternak
    J. Neurophysiol. 106, 1260-1273 (1 September 2011)

    Abnormal Presynaptic Short-Term Plasticity and Information Processing in a Mouse Model of Fragile X Syndrome
    P.-Y. Deng, D. Sojka, and V. A. Klyachko
    J. Neurosci. 31, 10971-10982 (27 July 2011)

    Highly Differentiated Projection-Specific Cortical Subnetworks
    M. Morishima, K. Morita, Y. Kubota, and Y. Kawaguchi
    J. Neurosci. 31, 10380-10391 (13 July 2011)

    Neural and computational mechanisms of postponed decisions
    M. Martinez-Garcia, E. T. Rolls, G. Deco, and R. Romo
    Proc. Natl. Acad. Sci. USA 108, 11626-11631 (12 July 2011)

    Post-tetanic increase in the fast-releasing synaptic vesicle pool at the expense of the slowly releasing pool
    J. S. Lee, W.-K. Ho, and S.-H. Lee
    JGP 136, 259-272 (1 September 2010)

    Beneficial Effects of the NMDA Antagonist Ketamine on Decision Processes in Visual Search
    K. Shen, S. Kalwarowsky, W. Clarence, E. Brunamonti, and M. Pare
    J. Neurosci. 30, 9947-9953 (21 July 2010)

    Neuronal Population Coding of Parametric Working Memory
    O. Barak, M. Tsodyks, and R. Romo
    J. Neurosci. 30, 9424-9430 (14 July 2010)

    Hierarchical Interaction Structure of Neural Activities in Cortical Slice Cultures
    G. S. Santos, E. D. Gireesh, D. Plenz, and H. Nakahara
    J. Neurosci. 30, 8720-8733 (30 June 2010)

    Temporal delays among place cells determine the frequency of population theta oscillations in the hippocampus
    C. Geisler, K. Diba, E. Pastalkova, K. Mizuseki, S. Royer, and G. Buzsaki
    Proc. Natl. Acad. Sci. USA 107, 7957-7962 (27 April 2010)

    Synaptic dynamics and decision making
    G. Deco, E. T. Rolls, and R. Romo
    Proc. Natl. Acad. Sci. USA 107, 7545-7549 (20 April 2010)

    Stimulation of the Frontal Eye Field Reveals Persistent Effective Connectivity after Controlled Behavior
    R. Akaishi, Y. Morishima, V. P. Rajeswaren, S. Aoki, and K. Sakai
    J. Neurosci. 30, 4295-4305 (24 March 2010)

    Neural Dynamics in Inferior Temporal Cortex during a Visual Working Memory Task
    L. Woloszyn, and D. L. Sheinberg
    J. Neurosci. 29, 5494-5507 (29 April 2009)

    Homeostatic Presynaptic Suppression of Neuronal Network Bursts
    D. Cohen, and M. Segal
    J. Neurophysiol. 101, 2077-2088 (1 April 2009)

    Intermittent ambiguous stimuli: Implicit memory causes periodic perceptual alternations
    J. W. Brascamp, J. Pearson, R. Blake, and A. V. van den Berg
    J Vis 9, 3-3 (1 March 2009)

    Broadband Coding with Dynamic Synapses
    B. Lindner, D. Gangloff, A. Longtin, and J. E. Lewis
    J. Neurosci. 29, 2076-2087 (18 February 2009)

    Interaction of Cellular and Network Mechanisms in Spatiotemporal Pattern Formation in Neuronal Networks
    A. Bogaard, J. Parent, M. Zochowski, and V. Booth
    J. Neurosci. 29, 1677-1687 (11 February 2009)

    State-, Timing-, and Pattern-Dependent Neuromodulation of Synaptic Strength by a Serotonergic Interneuron
    A. Sakurai, and P. S. Katz
    J. Neurosci. 29, 268-279 (7 January 2009)

    Memory traces in dynamical systems
    S. Ganguli, D. Huh, and H. Sompolinsky
    Proc. Natl. Acad. Sci. USA 105, 18970-18975 (2 December 2008)

    A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex
    H. Wang, G. G. Stradtman, X.-J. Wang, and W.-J. Gao
    Proc. Natl. Acad. Sci. USA 105, 16791-16796 (28 October 2008)

    Temporary Activation of Long-Term Memory Supports Working Memory
    J. A. Lewis-Peacock, and B. R. Postle
    J. Neurosci. 28, 8765-8771 (27 August 2008)

    NEUROSCIENCE: A Quiescent Working Memory
    S. Fusi, and B. R. Postle
    Science 319, 1495-1496 (14 March 2008)

    Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882