Skip to main content
SpringerLink
Log in

Effects of Neuromodulation in a Cortical Network Model of Object Working Memory Dominated by Recurrent Inhibition

  • Published:
Journal of Computational Neuroscience Aims and scope Submit manuscript

An Erratum to this article was published on 24 June 2014

Abstract

Experimental evidence suggests that the maintenance of an item in working memory is achieved through persistent activity in selective neural assemblies of the cortex. To understand the mechanisms underlying this phenomenon, it is essential to investigate how persistent activity is affected by external inputs or neuromodulation. We have addressed these questions using a recurrent network model of object working memory. Recurrence is dominated by inhibition, although persistent activity is generated through recurrent excitation in small subsets of excitatory neurons.

Our main findings are as follows. (1) Because of the strong feedback inhibition, persistent activity shows an inverted U shape as a function of increased external drive to the network. (2) A transient external excitation can switch off a network from a selective persistent state to its spontaneous state. (3) The maintenance of the sample stimulus in working memory is not affected by intervening stimuli (distractors) during the delay period, provided the stimulation intensity is not large. On the other hand, if stimulation intensity is large enough, distractors disrupt sample-related persistent activity, and the network is able to maintain a memory only of the last shown stimulus. (4) A concerted modulation of GABA A and NMDA conductances leads to a decrease of spontaneous activity but an increase of persistent activity; the enhanced signal-to-noise ratio is shown to increase the resistance of the network to distractors. (5) Two mechanisms are identified that produce an inverted U shaped dependence of persistent activity on modulation. The present study therefore points to several mechanisms that enhance the signal-to-noise ratio in working memory states. These mechanisms could be implemented in the prefrontal cortex by dopaminergic projections from the midbrain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abeles M (1991) Corticonics. Cambridge University Press, New York.

    Google Scholar 

  • Amit DJ (1995) The Hebbian paradigm reintegrated: Local reverberations as internal representations. Behav. Brain Sci. 18:617.

    Google Scholar 

  • Amit DJ, Brunel N (1997) Model of global spontaneous activity and local structured activity during delay periods in the cerebral cortex. Cerebral Cortex 7:237-252.

    Google Scholar 

  • Arnsten AFT (1998) Catecholamine modulation of prefrontal cortical cognitive function. Trends in Cognitive Sciences 2:436-447.

    Google Scholar 

  • Braitenberg V, Schütz A (1991) Anatomy of the Cortex. Springer-Verlag: Berlin.

    Google Scholar 

  • Brozoski TJ, Brown RM, Rosvold HE, Goldman PS (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science 205:929-932.

    Google Scholar 

  • Brunel N (2000) Persistent activity and the single cell f-I curve in a cortical network model. Network 11:261-280.

    Google Scholar 

  • Brunel N, Carusi F, Fusi S (1998) Slow stochastic Hebbian learning of classes in recurrent neural networks. Network 9:123-152.

    Google Scholar 

  • Brunel N, Hakim V (1999) Fast global oscillations in networks of integrate-and-fire neurons with low firing rates. Neural Comput. 11:1621-1671.

    Google Scholar 

  • Brunel N, Sergi S (1998) Firing frequency of integrate-and-fire neurons with finite synaptic time constants. J. Theor. Biol: 195:87-95.

    Google Scholar 

  • Burns BD, Webb AC (1976) The spontaneous activity of neurons in the cat's cerebral cortex. Proc. R. Soc. Lond. B 194:211-223.

    Google Scholar 

  • Cai JX, Anrsten AFT (1997) Dose-dependent effects of the dopamine D1 receptor agonists A77636 or SKF81297 on spatial working memory in aged monkeys. J. Pharmacol. Exp. Ther. 282:1-7.

    Google Scholar 

  • Camperi M, Wang XJ (1998) A model of visuospatial short-term memory in prefrontal cortex: Recurrent network and cellular bistability. J. Comput. Neurosci. 5:383-405.

    Google Scholar 

  • Cepeda C, Levine MS (1998) Dopamine and N-methyl-D-aspartate receptor interactions in the neostriatum. Dev. Neurosci. 20:1-18.

    Google Scholar 

  • Cepeda C, Radisavljevic Z, Peacock W, Levine MS, Buchwald NA (1992) Differential modulation by dopamine of responses evoked by excitatory amino acids in human cortex. Synapse 11:330-341.

    Google Scholar 

  • Compte A, Brunel N, Goldman-Rakic PS, Wang XJ (2000) Synaptic mechanisms and network dynamics underlying spatial working memory in a cortical network model. Cerebral Cortex 10:910-923.

    Google Scholar 

  • Condé F, Jacobowitz DM, Baimbridge KG, Lewis DA (1994) Local circuit neurons immunoreactive for calretinin, calbindin D-28k or parvalbumin in monkey prefrontal cortex: Distribution and morphology. J. Comp. Neurol. 341:95-116.

    Google Scholar 

  • Daniel DG, Weinberger DR, Jones DW, Zigun JR, Coppola R, Handel S, Bigelow LB, Goldberg TE, Berman KF, Kleinman JE (1991) The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia. J. Neurosci. 11: 1907-1917.

    Google Scholar 

  • Destexhe A, Mainen ZF, Sejnowski TJ (1998) Kinetic models of synaptic transmission. In: Koch C, Segev I, eds. Methods in Neuronal Modeling (2nd ed.). MIT Press, Cambridge, MA. pp. 1-25.

    Google Scholar 

  • Douglas RJ, Koch C, Mahowald M, Martin KM, Suarez HH (1995) Recurrent excitation in neocortical circuits. Science 269:981-985.

    Google Scholar 

  • Durstewitz D, Kelc M, Güntürkun O (1999) A neurocomputational theory of the dopaminergic modulation of working memory functions. J. Neurosci. 19:2807-2822.

    Google Scholar 

  • Durstewitz D, Seamans JK, Sejnowski TJ (2000) Dopamine-mediated stabilization of delay-period activity in a network model of prefrontal cortex. J. Neurophysiol. 83:1733-1750.

    Google Scholar 

  • Egan MF, Weinberger DR (1997) Neurobiology of schizophrenia. Curr. Opin. Neurobiol. 7:701-707.

    Google Scholar 

  • Funahashi S, Bruce CJ, Goldman-Rakic PS (1989) Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J. Neurophysiol. 61:331-349.

    Google Scholar 

  • Fuster JM, Alexander G (1971) Neuron activity related to short-term memory. Science 173:652-654.

    Google Scholar 

  • Fuster JM, Jervey JP (1981) Inferotemporal neurons distinguish and retain behaviourally relevant features of visual stimuli. Science 212:952-955.

    Google Scholar 

  • Gabbott PLA, Bacon SJ (1996) Local circuit neurons in the medial prefrontal cortex (areas 24a,b,c, 25 and 32) in the monkey. J. Comp. Neurol. 364:567-636.

    Google Scholar 

  • Gellman RL, Aghajanian GK (1993) Pyramidal cells in piriform cortex receive a convergence of inputs from monoamine activated GABAergic interneurons. Brain Res. 600:63-73.

    Google Scholar 

  • Goldman-Rakic PS (1987) Circuitry of primate prefrontal cortex and regulation of behavior by representational memory. In: Handbook of Physiology: The Nervous System V. American Physiological Society, Bethesda, MD. Chapter 9, pp. 373-417.

    Google Scholar 

  • Goldman-Rakic PS (1994) Working memory dysfunction in schizophrenia. J. Neuropsych. and Clin. Neurosci. 6:348-357.

    Google Scholar 

  • Goldman-Rakic PS (1995) Cellular basis of working memory. Neuron 14:477-485.

    Google Scholar 

  • Hansel D, Mato G, Meunier C, Neltner L (1998) On numerical simulations of integrate-and-fire neural networks. Neural Comput. 10:467-483.

    Google Scholar 

  • Hebb DO (1949) Organization of Behavior. Wiley, New York.

    Google Scholar 

  • Hestrin S, Sah P, Nicoll R (1990) Mechanisms generating the time course of dual component excitatory synaptic currents recorded in hippocampal slices. Neuron 5:247-253.

    Google Scholar 

  • Jahr CE, Stevens CF (1990) Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics. J. Neurosci. 10:3178-3182.

    Google Scholar 

  • Kawaguchi Y (1997) Selective cholinergic modulation of cortical GABAergic cell subtypes. J. Neurophysiol. 78:1743-1747.

    Google Scholar 

  • Koch KW, Fuster JM (1989) Unit activity in monkey parietal cortex related to haptic perception and temporary memory. Exp. Brain Res. 76:292-306.

    Google Scholar 

  • Kubota K, Niki H (1971) Prefrontal cortical unit activity and delayed alternation performance in monkeys. J. Neurophysiol. 34:337-347.

    Google Scholar 

  • Law-Tho D, Hirsch JC, Crepel F (1994) Dopamine modulation of synaptic transmission in rat prefrontal cortex: An in vitro electrophysiological study. Neurosci. Res. 21:151-160.

    Google Scholar 

  • Lorente de Nó R (1933) Vestibulo-ocular reflex arc. Arch. Neurol. Psych. 30:245-291.

    Google Scholar 

  • Mascaro M, Amit DJ (1999) Effective neural response function for collective population states. Network 10:351-373.

    Google Scholar 

  • McCormick D, Connors B, Lighthall J, Prince D (1985) Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons in the neocortex. J. Neurophysiol. 54:782-806.

    Google Scholar 

  • Miller EK, Erickson CA, Desimone R (1996) Neural mechanisms of visual working memory in prefrontal cortex of the macaque. J. Neurosci. 16:5154-5167.

    Google Scholar 

  • Miyashita Y (1988) Neuronal correlate of visual associative long-term memory in the primate temporal cortex. Nature 335:817-820.

    Google Scholar 

  • Miyashita Y, Chang HS (1988) Neuronal correlate of pictorial short-term memory in the primate temporal cortex. Nature 331:68-70.

    Google Scholar 

  • Muly III EC, Szigeti K, Goldman-Rakic PS (1998) D1 receptor in interneurons of macaque prefrontal cortex: Distribution and subcellular localization. J. Neurosci. 18:10553-10565.

    Google Scholar 

  • Murray JD (1993) Mathematical Biology. Springer-Verlag, Berlin.

    Google Scholar 

  • Nakamura K, Kubota K (1995) Mnemonic firing of neurons in the monkey temporal pole during a visual recognition memory task. J. Neurophysiol. 74:162-178.

    Google Scholar 

  • Nicola SM, Surmeier DJ, Malenka RC (2000) Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Ann. Rev. Neurosci. 23:185-215.

    Google Scholar 

  • Okubo Y, Suhara T, Suzuki K, Kobayashi K, Inoue O, Terasaki O, Someya Y, Sassa T, Sudo Y, Matsushima E, Iyo M, Tateno Y, Toru M (1997) Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 385:634-636.

    Google Scholar 

  • Penit-Soria J, Audinat E, Crepel F (1987) Excitation of rat prefrontal cortical neurons by dopamine: An in vitro electrophysiological study. Brain Res. 425:263-274.

    Google Scholar 

  • Pinto DJ, Brumberg JC, Simons DJ, Ermentrout GB (1996) A quantitative population model of whisker barrels: Re-examining the Wilson-Cowan equations. J. Comput. Neurosci. 3:247-264.

    Google Scholar 

  • Press WH, Teukolsky SA, Vetterling WT, Flannery BP (1992) Numerical Recipes in C. Cambridge University Press, Cambridge.

    Google Scholar 

  • Rao SG, Williams GV, Goldman-Rakic PS (1999) Isodirectional tuning of adjacent interneurons and pyramidal cells during working memory: Evidence for microcolumnar organization in PFC. J. Neurophysiol. 81:1903-1916.

    Google Scholar 

  • Salin PA, Prince DA (1996) Spontaneous GABAA receptor mediated inhibitory currents in adult rat somatosensory cortex. J. Neurophysiol. 75:1573-1588.

    Google Scholar 

  • Sawaguchi T, Goldman-Rakic PS (1991) D1 dopamine receptors in prefrontal cortex: Involvement in working memory. Science 251:947-950.

    Google Scholar 

  • Sawaguchi T, Matsumara M, Kubota K (1990) Catecholaminergic effects on neuronal activity related to a delayed response task in monkey prefrontal cortex. J. Neurophysiol. 63:1385-1400.

    Google Scholar 

  • Servan-Schreiber D, Printz H, Cohen JD (1990) A network model of catecholamine effects: gain, signal-to-noise ratio, and behavior. Science 249:892-895.

    Google Scholar 

  • Shadlen MN, Newsome WT (1994) Noise, neural codes and cortical organization. Current Opinion in Neurobiol. 4:569-579.

    Google Scholar 

  • Somers DC, Nelson SB, Sur M (1995) An emergent model of orientation selectivity in cat visual cortical simple cells. J. Neurosci. 15:5448-5465.

    Google Scholar 

  • Spruston N, Jonas P, Sakmann B (1995) Dendritic glutamate receptor channel in rat hippocampal CA3 and CA1 pyramidal neurons. J. Physiol. 482:325-352.

    Google Scholar 

  • Troyer TW, Krukowski AE, Priebe NJ, Miller KD (1998) Contrast-invariance orientation tuning in cat visual cortex: Thalamocortical input tuning and correlation-based intracortical connectivity. J. Neurosci. 18:5908-5927.

    Google Scholar 

  • Tsodyks MV, Sejnowski T (1995) Rapid state switching in balanced cortical network models. Network 6:111-124.

    Google Scholar 

  • Tuckwell HC (1988) Introduction to Theoretical Neurobiology. Cambridge University Press, Cambridge.

    Google Scholar 

  • Umemiya M, Raymond LA (1997) Dopaminergic modulation of excitatory postsynaptic currents in rat neostriatal neurons. J. Neurophysiol. 78:1248-1255.

    Google Scholar 

  • van Vreeswijk C, Sompolinsky H (1996) Chaos in neuronal networks with balanced excitatory and inhibitory activity. Science 274:1724-1726.

    Google Scholar 

  • Wang XJ (1999) Synaptic basis of cortical persistent activity: The importance of NMDA receptors to working memory. J. Neurosci. 19:9587-9603.

    Google Scholar 

  • Williams GV, Goldman-Rakic PS (1995) Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 376:572-575.

    Google Scholar 

  • Wilson FAW, Scalaidhe SPO, Goldman-Rakic PS (1993) Dissociation of object and spatial processing domains in primate prefrontal cortex. Science 260:1955-1958.

    Google Scholar 

  • Wilson FAW, Scalaidhe SPO, Goldman-Rakic PS (1994) Functional synergism between putative γ-aminobutyrate-containing neurons and pyramidal neurons in prefrontal cortex. Proc. Natl. Acad. Sci. USA 91:4009-4013.

    Google Scholar 

  • Wilson HR, Cowan JD (1973) A mathematical theory of the functional dynamics of cortical and thalamic nervous tissue. Kybernetik 13:55-80.

    Google Scholar 

  • Xiang Z, Huguenard JR, Prince DA (1998) GABAA receptor mediated currents in interneurons and pyramidal cells of rat visual cortex. J. Physiol. 506:715-730.

    Google Scholar 

  • Yakovlev V, Fusi S, Berman E, Zohary E (1998) Inter-trial neuronal activity in inferior temporal cortex: A putative vehicle to generate long-term visual associations. Nature Neurosci. 1:310-317.

    Google Scholar 

  • Yang CR, Seamans JK, Gorelova N (1996) Electrophysiological and morphological properties of layer V-VI principal pyramidal cells in rat prefrontal cortex in vitro. J. Neurosci. 16:1904-1921.

    Google Scholar 

  • Zahrt J, Taylor JR, Mathew RG, Arnsten AFT (1997) Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance. J. Neurosci. 17:8528-8535.

    Google Scholar 

  • Zheng P, Zhang XX, Bunney BS, Zhi WX (1999) Opposite modulation of cortical N-methyl-D-aspartate receptor-mediated responses by low and high concentrations of dopamine. Neuroscience 91:527-535.

    Google Scholar 

  • Zhou FM, Hablitz JJ (1999) Dopamine modulation of membrane and synaptic properties of interneurons in rat cerebral cortex. J. Neurophysiol. 81:967-976.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. LPS, Ecole Normale Supérieure, 24 rue Lhomond, 75231, Paris Cedex 05, France

    Nicolas Brunel

  2. Volen Center for Complex Systems, Brandeis University, 415 South St., Waltham, MA, 02254-9110, USA

    Xiao-Jing Wang

Authors
  1. Nicolas Brunel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Jing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s10827-014-0506-8.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brunel, N., Wang, XJ. Effects of Neuromodulation in a Cortical Network Model of Object Working Memory Dominated by Recurrent Inhibition. J Comput Neurosci 11, 63–85 (2001). https://doi.org/10.1023/A:1011204814320

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011204814320

Search

Navigation