Abstract
A network model of simplified striatal principal neurons with mutual inhibition was used to investigate possible interactions between cortical glutamatergic and nigral dopaminergic afferents in the neostriatum. Glutamatergic and dopaminergic inputs were represented by an excitatory synaptic conductance and a slow membrane potassium conductance, respectively. Neuronal activity in the model was characterized by episodes of increased action potential firing rates of variable duration and frequency. Autocorrelation histograms constructed from the action potential activity of striatal model neurons showed that reducing peak excitatory conductance had the effect of increasing interspike intervals. On the other hand, the maximum value of the dopamine-sensitive potassium conductance was inversely related to the duration of firing episodes and the maximal firing rates. A smaller potassium conductance restored normal firing rates in the most active neurons at the expense of a larger proportion of neurons showing reduced activity. Thus, a homogeneous network with mutual inhibition can produce equally complex dynamics as have been proposed to occur in a striatal network with two neuron populations that are oppositely regulated by dopamine. Even without mutual inhibition it appears that increased dopamine concentrations could partially compensate for the effects of reduced glutamatergic input in individual neurons.
Similar content being viewed by others
References
Akaike A, Ohno Y, Sasa M, Takaori S (1987) Excitatory and inhibitory effects of dopamine on neuronal activity of the caudate nucleus neurons in vitro.Brain Res. 418:262–272.
Akaike A, Sasa M, Takaori S (1988) Muscarinic inhibition as a dominant role in cholinergic regulation of transmission in the caudate nucleus.J. Pharmacol. Exp. Ther. 246:1129–1136.
Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders.Trends Neurosci. 12:366–375.
Aldridge JW, Gilman S (1991) The temporal structure of spike trains in the primate basal ganglia: Afferent regulation of bursting demonstrated with precentral cerebral cortical ablation.Brain Res. 543:123–138.
Amari SI (1977) Dynamics of pattern formation in lateral-inhibition type neural fields.Biol. Cybern. 27:77–87.
Arbuthnott GW, Ingham CA (1993) The thorny problem of what dopamine does in psychiatric disease. In: GW Arbuthnott, PC Emson, eds. Chemical Signalling in the Basal Ganglia. Elsevier, Amsterdam, pp. 341–350.
Bargas J, Galarraga E, Aceves J (1988) Electrotonic properties of neostriatal neurons are modulated by extracellular potassium.Exp. Brain Res. 72:390–398.
Bell AJ, Mainen ZF, Sejnowski TJ (1994) ‘Balancing’ of conductances may explain irregularity of cortical spiking. In: JM Bower, ed. Abstracts of the Third Annual Computation and Neural Systems Meeting, Monterey, CA. p. 11.
Bernard C, Axelrad H, Giraud BG (1993) Effects of collateral inhibition in a model of the immature rat cerebellar cortex: Multineuron correlations.Cognitive Brain Res. 1:100–122.
Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations.J. Neurol. Sci. 20:415–455.
Bishop GA, Chang HT, Kitai ST (1982) Morphological and physiological properties of neostriatal neurons: An intracellular horseradish peroxidase study in the rat.Neurosci. 7:179–191.
Brooks DJ (1993) PET studies on the early and differential diagnosis of Parkinson's disease.Neurology 43(Suppl. 6):S6-S16.
Calabresi P, Benedetti M, Mercuri MB, Bernardi G (1988) Endogenous dopamine and dopaminergic agonists modulate synaptic excitation in neostriatum: Intracellular studies from naive and catecholamine-depleted rats.Neurosci. 27:145–157.
Calabresi P, Mercuri NB, Bernardi G (1990b) Synaptic and intrinsic control of membrane excitability of neostriatal neurons. II. An in vitro analysis.J. Neurophysiol. 63:663–675.
Calabresi P, Mercuri NB, Sancesario G, Bernardi G (1993) Electrophysiology of dopamine-denervated striatal neurons.Brain 116:433–452.
Calabresi P, Mercuri N, Stanzione P, Stefani A, Bernardi G (1987b) Intracellular studies on the dopamine-induced firing inhibition of neostriatal neurons in vitro: Evidence for D1 receptor involvement.Neurosci. 20:757–771.
Calabresi P, Mercuri NB, Stefani A, Bernardi G (1990a) Synaptic and intrinsic control of membrane excitability of neostriatal neurons. I. An in vivo analysis.J. Neurophysiol. 63:651–662.
Calabresi P, Misgeld U, Dodt HU (1987a) Intrinsic membrane properties of neostriatal neurons can account for their low level of spontaneous activity.Neurosci. 20:293–303.
Cepeda C, Walsh JP, Hull CD, Howard SG, Buchwald NA, Levine MS (1989) Dye-coupling in the neostriatum of the rat: I. Modulation by dopamine-depleting lesions.Synapse 4:229–237.
Cherubim E, Herrling PL, Lanfumey L, Stanzione P (1988) Excitatory amino acids in synaptic excitation of rat striatal neurones in vitro.J. Physiol. 400:677–690.
Chiodo LA, Berger TW (1986) Interactions between dopamine and amino acid-induced excitation and inhibition in the striatum.Brain Res. 375:198–203.
Connolly CI, Burns JB (1993) A model for the functioning of the striatum.Biol. Cybern. 68:535–544.
Connor JD (1970) Caudate nucleus neurones: Correlation of the effects of substantia nigra stimulation with iontophoretic dopamine.J. Physiol. 208:691–703.
Fisher RS, Buchwald NA, Hull CD, Levine MS (1986) Neurons of origin of striatonigral axons in the cat: Connectivity and Golgi markers of somatodendritic architecture.Brain Res. 397:173–180.
Freund TF, Bolam JP, Björklund A, Stenevi U, Dunnett SB, Powell JF, Smith AD (1985) Efferent synaptic connections of grafted dopaminergic neurons reinnervating the host neostriatum: A tyrosine hydroxylase immunocytochemical study.J. Neurosci. 5:603–616.
Freund TF, Powell JF, Smith AD (1984) Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons, with particular reference to dendritic spines.Neurosci. 13:1189–1215.
Galarraga E, Bargas J, Sierra A, Aceves J (1989) The role of calcium in the repetitive firing of neostriatal neurons.Exp. Brain Res. 75:157–168.
Gerfen CR, Enger TM, Mahan LC, Susel Z, Chase TN, Monsma FJ, Sibley DR (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons.Science 250:1429–1432.
Gerfen CR, McGinty JF, Young WS (1991) Dopamine differentially regulates dynorphin, substance P, and enkephalin expression in striatal neurons: in situ hybridization histochemical analysis.J. Neurosci. 11:1016–1031.
Greenamyre JT (1993) Glutamate-dopamine interactions in the basal ganglia: Relationship to Parkinson's disease.J. Neural Transm. 91:255–269.
Groves PM (1983) A theory of the functional organization of the neostriatum and the neostriatal control of voluntary movement.Brain Res. Rev. 5:109–132.
Hattori T, Fibiger HC (1982) On the use of lesions of afferents to localize neurotransmitter receptor sites in the striatum.Brain Res. 238:245–256.
Herrling PL (1985) Pharmacology of the corticocaudate excitatory postsynaptic potential in the cat: Evidence for its mediation by quisqualate- or kainate-receptors.Neurosci. 14:417–426.
Herrling PL, Hull CD (1980) Iontophoretically applied dopamine depolarizes and hyperpolarizes the membrane of cat caudate neurons.Brain Res. 192:441–462.
Herrling PL, Morris R, Salt TE (1983) Effects of excitatory amino acids and their antagonists on membrane and action potentials of cat caudate neurones.J. Physiol Lond. 339:207–222.
Hoffman JM, Hawk TC (1993) Positron emission tomographic study of pre- and postsynaptic function in Parkinson's disease. In: JS Schneider, M Gupta, eds. Current Concepts in Parkinson's Disease Research. Hogrefe & Huber, Seattle, pp. 273–296.
Ingham CA, Hood SH, Arbuthnott GW (1991) A light and electron microscopy study of enkephalin-immunoreactive structures in the rat neostriatum after removal of the nigrostriatal dopaminergic pathways.Neurosci. 42:715–730.
Ingham CA, Hood SH, Van Maldegem B, Weenink A, Arbuthnott GW (1993) Morphological changes in the rat neostriatum after unilateral 6-hydroxydopamine injections into the nigrostriatal pathway.Exp. Brain Res. 93:17–27.
Jaeger D, Kita H, Wilson CJ (1994) Surround inhibition among projection neurons is weak or nonexistent in the rat neostriatum.J. Neurophysiol. 72:2555–2558.
Jiang ZG, North RA (1991) Membrane properties and synaptic responses of rat striatal neurons in vitro.J. Physiol. 443:533–553.
Jimenez-Castellanos J, Graybiel AM (1989) Evidence that histochemically distinct zones of the primate substantia nigra pars compacta are related to patterned distributions of nigrostriatal projection neurons and striatonigral fibers.Exp. Brain Res. 74: 227–238.
Kanazawa I, Kimura M, Murata M, Tanaka Y, Cho F (1990) Choreic movements in the macaque monkey induced by kainic acid lesions of the striatum combined with L-DOPA. Pharmacological, biochemical and physiological studies on neural mechanisms.Brain 113:509–535.
Kawaguchi Y, Wilson CJ, Emson PC (1989) Intracellular recording of identified neostriatal patch and matrix spiny cells in a slice preparation preserving cortical inputs.J. Neurophysiol. 62:1052–1068.
Kornhuber J, Kornhuber ME (1986) Presynaptic dopaminergic modulation of cortical input to the striatum.Life Sci. 39:669–674.
Kötter R (1994) Postsynaptic integration of glutamatergic and dopaminergic signals in the striatum.Prog. Neurobiol. 44:163–196.
Lidsky TI, Manetto C, Schneider JS (1985) A consideration of sensory factors involved in motor functions of the basal ganglia.Brain Res. Rev. 9:133–146.
Lighthall JW, Kitai ST (1983) A short duration GABAergic inhibition in identified neostriatal medium spiny neurons: In vitro slice study.Brain Res. Bull. 11:103–110.
Markham CH (1987) The “motor” vs. “sensory” enigma in Parkinson's disease. In: JS Schneider, TI Lidsky, eds. Basal Ganglia and Behavior: Sensory Aspects of Motor Functioning. Hans Huber, Toronto. pp. 161–167.
McNeill TH, Brown SA, Rafols JA, Shoulson I (1988) Atrophy of medium spiny I striatal dendrites in advanced Parkinson's disease.Brain Res. 455:148–152.
Mercuri NB, Bernardi G, Calabresi P, Cotugno A, Levi G, Stanzione P (1985) Dopamine decreases cell excitability in rat striatal neurons by pre- and postsynaptic mechanisms.Brain Res. 358:110–121.
Misgeld U, Wagner A, Ohno T (1982) Depolarizing IPSPs and depolarization by GABA of rat neostriatum cells in vitro.Exp. Brain Res. 45:108–114.
Nicole S (1992) Effects of Iahp on pattern recall and the synchronization of firing.Network 3:369–378.
Nisenbaum ES, Berger TW (1992a) Functionally distinct subpopulations of striatal neurons are differentially regulated by GABAergic and dopaminergic inputs-I. In vivo analysis.Neurosci. 48:561–578.
Nisenbaum ES, Grace AA, Berger TW (1992b) Functionally distinct subpopulations of striatal neurons are differentially regulated by GABAergic and dopaminergic inputs-II. In vitro analysis.Neurosci. 48:579–593.
Orr WB, Gardiner TW, Stricker EM, Zigmond MJ, Berger TW (1986) Short-term effects of dopamine-depleting brain lesions on spontaneous activity of striatal neurons: Relation to local dopamine concentration and behavior.Brain Res. 376:20–28.
Pasik P, Pasik T, Holstein GR, Hámori J (1988) GABAergic elements in the neuronal circuitry of the monkey neostriatum: A light and electron microscopic immunocytochemical study.J. Comp. Neurol. 270:157–170.
Rall W, Burke RE, Holmes WR, Jack JJB, Redman SJ, Segev I (1992) Matching dendritic neuron models to experimental data.Physiol. Rev. 72(Suppl.):S159-S186.
Roberts PJ, McBean GJ, Sharif NA, Thomas EM (1982) Striatal glutamatergic function: Modifications following specific lesions.Brain Res. 235:83–91.
Rutherford A, Garcia-Munoz M, Arbuthnott GW (1988) An afterhyperpolarization recorded in striatal cells ‘in vitro’: Effect of dopamine administration.Exp. Brain Res. 71:399–405.
Ryan LJ, Tepper JM, Young SJ, Groves PM (1986) Frontal cortex stimulation evoked neostriatal potentials in rats: Intracellular and extracellular analysis.Brain Res. Bull. 17:751–758.
Samuel D, Kumar U, Nieoullon A (1988) Gamma-aminobutyric acid function in the rat striatum is under the double influence of nigrostriatal dopaminergic and thalamostriatal inputs: Two modes of regulation?J. Neurochem. 51:1704–1710.
Schneider JS, Roeltgen DP (1993) Sensorimotor dysfunctions in Parkinson's disease: Clues from human and animal studies. In: JS Schneider, M Gupta, eds. Current Concepts in Parkinson's Disease Research. Hogrefe & Huber, Seattle, pp. 59–69.
Schröder KF, Hopf A, Lange H, Thörner G (1975) Morphometrischstatistische Strukturanalysen des Striatum, Pallidum and Nucleus subthalamicus beim Menschen. I. Striatum.J. Hirnforsch. 16:333–350.
Schultz W (1982) Depletion of dopamine in the striatum as an experimental model of Parkinsonism: Direct effects and adaptive mechanisms.Prog. Neurobiol. 18:121–166.
Schultz W, Ungerstedt U (1978) Short-term increase and long-term reversion of striatal cell activity after degeneration of the nigrostriatal dopamine system.Exp. Brain Res. 33:159–171.
Segovia J, Tillakaratne NJK, Whelan K, Tobin AJ, Gale K (1990) Parallel increases in striatal glutamic acid decarboxylase activity and mRNA levels in rats with lesions of the nigrostriatal pathway.Brain Res. 529:345–348.
Siggins GR (1978) Electrophysiological role of dopamine in striatum: Excitatory or inhibitory? In: MA Lipton, A DiMascio, KF Killam, eds. Psychopharmacology: A Generation of Progress. Raven, New York. pp. 143–157.
Siggins GR, Hoffer BJ, Bloom FE, Ungerstedt U (1976) Cytochemical and electrophysiological studies of dopamine in the caudate nucleus. In: MD Yahr, ed. The Basal Ganglia. Raven, New York, p. 227.
Skinner FK, Kopell N, Marder E (1994) Mechanisms for oscillation and frequency control in reciprocally inhibitory model neural networks.J. Comput. Neurosci. 1:69–87.
Smith AD, Bolam JP (1990) The neural network of the basal ganglia as revealed by the study of synaptic connections of identified neurones.Trends Neurosci. 13:259–265.
Softky WR, Koch C (1993) The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs.J. Neurosci. 13:334–350.
Sugimori M, Preston RI, Kitai ST (1978) Response properties and electrical constants of caudate neurons in cat.J. Neurophysiol. 41:1662–1675.
Surmeier DJ, Bargas J, Kitai ST (1988) Voltage-clamp analysis of a transient potassium current in rat neostriatal neurons.Brain Res. 473:187–192.
Surmeier DJ, Kitai ST (1993) D1 and D2 dopamine receptor modulation of sodium and potassium currents in rat neostriatal neurons. In: GW Arbuthnott, PC Emson, eds. Chemical Signalling in the Basal Ganglia. Elsevier, Amsterdam, pp. 309–324.
Surmeier DJ, Wilson CJ, Eberwine J (1994) Patch-clamp techniques for studying potassium currents in mammalian brain neurons. In: T Narahashi, ed. Ion Channels of Excitable Cells. Academic, San Diego. pp. 39–67.
Surmeier DJ, Xu ZC, Wilson CJ, Stefani A, Kitai ST (1992) Grafted neostriatal neurons express a late-developing transient potassium current.Neurosci. 48:849–856.
Twery MJ, Thompson LA, Walters JR (1993) Electrophysiological characterization of rat striatal neurons in vitro following a unilateral lesion of dopamine cells.Synapse 13:322–332.
Wang XJ, Rinzel J (1992) Alternating and synchronous rhythms in reciprocally inhibitory model neurons.Neural Comp. 4:84–97.
Wickens JR, Alexander ME, Miller R (1991) Two dynamic modes of striatal function under dopaminergic-cholinergic control: Simulation and analysis of a model.Synapse 8:1–12.
Wickens JR, Kötter R, Alexander ME (in press) Effects of local connectivity on striatal function: Simulation and analysis of a model.Synapse.
Wilson CJ (1986) Three dimensional analysis of dendritic spines by means of HVEM.J. Electron Microscopic Tech. 35(Suppl.):1151–1155.
Wilson CJ (1990) Basal ganglia. In: GM Shepherd, ed. The Synaptic Organization of the Brain. Oxford University Press, New York, pp. 279–316.
Wilson CJ (1992) Dendritic morphology, inward rectification, and the functional properties of neostriatal neurons. Single Neuron Computation. Neural Nets: Foundations to Applications. Academic Press, San Diego. pp. 141–171.
Wilson CJ (1993) The generation of natural firing patterns in neostriatal neurons. In: GW Arbuthnott, PC Emson, eds. Chemical Signalling in the Basal Ganglia. Elsevier, Amsterdam, pp. 277–297.
Wilson CJ, Chang HT, Kitai ST (1982) Origins of postsynaptic potentials evoked in identified rat neostriatal neurons by stimulation in substantia nigra.Exp. Brain Res. 45:157–167.
Wilson MA, Bower JM (1989) The simulation of large-scale neural networks. In: C Koch, I Segev, eds. Methods in Neuronal Modeling. From Synapses to Network. MIT Press, Cambridge, MA. pp. 291–333.
Wolfram S (1991) Mathematica: A system for doing mathematics by computer. Addison-Wesley, Redwood City.
Xu ZC, Wilson CJ, Emson PC (1992) Morphology of intracellularly stained spiny neurons in rat striatal grafts.Neurosci. 48:95–110.
Yeterian EJ, Van Hoesen GW (1978) Cortico-striate projections in the rhesus monkey: The organization of certain cortico-caudate connections.Brain Res. 139:43–63.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kötter, R., Wickens, J. Interactions of glutamate and dopamine in a computational model of the striatum. J Comput Neurosci 2, 195–214 (1995). https://doi.org/10.1007/BF00961434
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00961434