Journal of Computational Neuroscience

, Volume 6, Issue 1, pp 49–69 | Cite as

Sodium Dynamics Underlying Burst Firing and Putative Mechanisms for the Regulation of the Firing Pattern in Midbrain Dopamine Neurons: A Computational Approach

  • C.C. Canavier
Article

Abstract

A physiologically based multicompartmental computational model of a midbrain dopamine (DA) neuron, calibrated using data from the literature, was developed and used to test the hypothesis that sodium dynamics drive the generation of a slow oscillation postulated to underlie NMDA-evoked bursting activity in a slice preparation. The full compartmental model was reduced to three compartments and ultimately to two variables, while retaining the biophysical interpretation of all parameters. A phase-plane analysis then suggested two mechanisms for the regulation of the firing pattern: (1) bursting activity is favored by manipulations that enhance the region of negative slope in the whole-cell IV curve and inhibited by those manipulations, such as increasing linear currents, that tend to dampen this region and (2) assuming a region of negative slope is present in the IV curve, the bias of the system can be altered, either enabling or disabling bursting. The model provides a coherent framework for interpreting the effects of glutamate, aspartate, NMDA, and GABA agonists and antagonists under current-clamp conditions, as well as the effects of NMDA and barium under voltage-clamp conditions.

neurouodulation VTA substantia nigra neural oscillator 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bayer VE, Pickel VM (1991) GABA-labeled terminals form proportionately more synapses with dopaminergic neurons containing low densities of tyrosine hydroxylase-immunoreactivity in rat ventral tegmental area. Brain Res. 559:44–55.Google Scholar
  2. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntingdon: Clinical, morphological, and neurochemical correlations. J. Neurosci. 20:415–455.Google Scholar
  3. Brozoski TJ, Brown RM, Rosvold HE, Goldman PS (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex. Science 205:929–932.Google Scholar
  4. Cardozo DL, Bean BP (1995) Voltage-dependent calcium channels in rat midbrain dopamine neurons: Modulation by dopamine and GABAB receptors. J. Neurophysiol. 74:1137–1148.Google Scholar
  5. Carter CJ (1982) Topographical distribution of possible glutaminergic pathways from the frontal cortex to the stratum and substantia nigra in rats. Neuropharmacology 21:379–383.Google Scholar
  6. Celada P, Paladini C, Tepper J (in press) Gabaergic control of rat substantia nigra dopaminergic neurons: Role of globus pallidus and substantia nigra pars reticulata.Google Scholar
  7. Charlety PJ, Grenhoff J, Chergui K, Svensson TH, Chouvet G (1991) Burst firing of mesencephalic dopamine neurons is inhibited by somatodendritic application of kynurenate. Acta Physiol. Scand. 142:105–112.Google Scholar
  8. Chergui K, Akaoka H, Charlety PJ, Saunier CF, Buda M, Chouvet G (1994) Subthalamic nucleus modulates burst firing of nigral dopamine neurons via NMDA receptors. Neuroreport 5:1185–1188.Google Scholar
  9. Chergui K, Charlety PJ, Akaoka H, Saunier CF, Brunet JL, Buda M, Svensson TH, Chouvet G (1993) Tonic activation of NMDA receptors causes spontaneous burst discharge of rat midbrain neurons in vitro. Eur. J. Neurosci. 5:137–144.Google Scholar
  10. Chergui K, Nomikos GG, Methe JM, Gonon FG, Svensson TH (1996) Burst stimulation of the medial forebrain bundle selectively increases fos-like immunoreactivity in the limbic forebrain of the rat. Neurosci. 72:141–156.Google Scholar
  11. Christoffersen CL, Meltzer LT (1995) Evidence for N-methyl-Daspartate and AMPA subtypes of the glutamate receptor on substantia nigra dopamine neurons: Possible preferential role for Nmethyl-D-aspartate receptors. Neurosci. 67:373–381.Google Scholar
  12. DeWeer P, Rakowski RF (1984) Current generated by the backwardrunning electrogenic Na pump in squid giant axons. Nature 309:450–452.Google Scholar
  13. Engberg G, Kling-Petersen T, Nissbrandt H (1993) GABAB receptor-activation alters the firing pattern of dopamine neurons in the rat substantia nigra. Synapse 15:229–338.Google Scholar
  14. Fleck M, Henze D, Barrionuevo G, Palmer AM (1993) Aspartate and glutamate mediate excitatory synaptic transmission in area CA1 of the hippocampus. J. Neurosci. 13:3944–3955.Google Scholar
  15. Freeman AS, Meltzer LT, Bunney BS (1985) Firing properties of substantia nigra dopaminergic neurons in freely moving rats. Life Sciences 36:1983–1994.Google Scholar
  16. Fujimura K, Matsuda Y (1989) Autogenous oscillatory potentials in the neurons of the guinea pig substantia nigra pars compacta in vitro. Neurosci. Lett. 104:53–57.Google Scholar
  17. Gariano RF, Groves PM (1988) Burst firing induced in midbrain dopamine neurons by stimulation of the medial prefrontal and anterior cingulate cortices. Brain Res. 462:194–198.Google Scholar
  18. Glitsch HG, Krahn T, Pusch H (1989) The dependence of the sodium pump current on internal Na concentration and membrane potential in cardioballs from sheep purkinje fibres. Pflügers Arch. 414:52–58.Google Scholar
  19. Gonon FG (1988) Nonlinear relationship between impulse flow and dopamine release by rat midbrain dopaminergic neurons as studied by in vivo electrochemistry. Neurosci. 24:19–28.Google Scholar
  20. Grace AA, Bunney BS (1984) The control of firing pattern in nigral dopamine neurons: Burst firing. J. Neurosci. 4:2877–2890.Google Scholar
  21. Grace AA, Onn SP (1989) Morphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro. J. Neurosci. 9:3463–3481.Google Scholar
  22. Gu X, Blatz AL, German DC (1992) Subtypes of substantia nigra dopaminergic neurons revealed by apamin: Autoradiographic and electrophysiological studies. Brain Res. Bull. 28:435–440.Google Scholar
  23. Hairer E, Wanner G (1991) Solving Ordinary Differential Equations II: Stiff and Differential-Algebraic Problems. Springer Series in Computational Mathematics. Springer Verlag, New York.Google Scholar
  24. Hausser M, Stuart G, Racca C, Sakmann B (1995) Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons. Neuron 15:637–647.Google Scholar
  25. Hines M (1993) NEURON: A program for simulation of nerve equations. In: FH Eeckman, ed. Neural Systems: Analysis and Modeling. Kluwer Academic Publishers, Norwell, MA. pp. 127–136.Google Scholar
  26. Hökfelt T, Everitt BJ, Theodorsson-Norheim E, Goldstein M (1984) Occurrence of neurotensin-like immunoreactivity in subpopulations of hypothalamic, mesencephalic and medullary catecholamine neurons. J. Comp. Neurol. 222:543–559.Google Scholar
  27. Hökfelt T, Skirbol L, Rehfeld JF, Goldstein M, Markey K, Dann O (1980) A subpopulation of mesencephalic dopamine neurons projecting to limbic areas contains a cholecystokinin-like peptide: Evidence from immunohistochemistry combined with retrograde tracing. Neurosci. 5:2093–4124.Google Scholar
  28. Ip NY, Zigmond RE (1984) Pattern of presynaptic nerve activity can determine the type of neurotransmitter regulating a postsynaptic event. Nature 311:472–474.Google Scholar
  29. Johnson SW, North RA (1992) Two types of neuron in the rat ventral tegmental area and their synaptics inputs. J. Physiol. 450:455–468.Google Scholar
  30. Johnson SW, Seutin V (1997) Bicuculline methiodide potentiates NMDA-dependent burst firing by blocking apamin-sensitive Ca2+-activated K+ currents in rat dopamine neurons. Soc. Neurosci. Abstr. 23:1210.Google Scholar
  31. Johnson SW, Seutin V, North RA (1992) Burst-firing in dopamine neurons induced by N-methyl-D-aspartate: Role of electrogenic sodium pump. Science 258:665–667.Google Scholar
  32. Johnston D, Wu SMS (1995) Foundations of Cellular Neurophysiology. MIT Press, Cambridge, MA.Google Scholar
  33. Juraska JM, Wilson CJ, Groves PM (1977) The substantia nigra of the rat: A Golgi study. J. Comp. Neurol. 172:585–600.Google Scholar
  34. Kang Y, Kitai ST (1993) A whole cell patch-clamp study on the pacemaker potential in dopaminergic neurons of rat substantia nigra compacta. Neurosci. Res. 18:209–221.Google Scholar
  35. Koob GF, Vaccarino FJ, Amalric M, Bloom FE (1987) Positive reinforcement properties of drugs: Search for neural substrates. In: J Engel, L Oreland, eds. Brain Reward Systems and Abuse. Raven Press, New York. p. 35.Google Scholar
  36. Kushmerick MJ, Podolsky RJ (1969) Ionic mobility in muscle cells. Science 166:1297–1298.Google Scholar
  37. Lacey MG, Mercuri NB, North AR (1988) On the potassium conductance increase activated by GABAB and dopamine D2 receptors in rat substantia nigra neurones. J. Physiol. 401:437–453.Google Scholar
  38. Li YL, Bertram R, Rinzel J (1996) Modeling NMDA-induced bursting in dopamine neurons. Neurosci. 71:397–410.Google Scholar
  39. Ljungberg T, Apicella P, Schultz W (1992) Responses of monkey dopamine neurons during learning of behavioral reactions. J. of Neurophysiol. 67:145–163.Google Scholar
  40. Marder E, Abbott LF (1995) Theory in motion. Curr. Opin. Neur. 5:832–840.Google Scholar
  41. Mathé JM, Chergui K, Engberg G, Svensson TH (1996) GABAB receptors modulate the firing pattern of dopamine neurons in the ventral tegmental area. Soc. Neurosci. Abstr. 22:357.Google Scholar
  42. Mayer ML, Westbrook GL (1987) Permeation and block of Nmethyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones. J. Physiol. 394:501–527.Google Scholar
  43. Mercuri NB, Bonci A, Calabresi P, Stefani A, Bernardi G (1995) Properties of the hyperpolarization-activated cation current I H in rat midbrain dopaminergic neurons. Euro. J. Neurosci. 7:462–469.Google Scholar
  44. Mercuri NB, Bonci A, Calabresi P, Stratta F, Stefani A, Bernardi G (1994) Effects of dihydropyridine calcium antagonists on rat midbrain dopaminergic neurones. Br. J. Pharmacol. 113:831–838.Google Scholar
  45. Mercuri NB, Stratta F, Calabresi P, Bernardi G (1992) A voltageclamp analysis of NMDA-induced responses on dopaminergic neurons of the rat substantia nigra zona compacta and ventral tegmental area. Brain Res. 593:51–56.Google Scholar
  46. Mereu G, Costa E, Armstrong DM, VS (1991) Glutamate receptor subtypes mediate excitatory synaptic currents of dopamine neurons in midbrain slices. J. Neurosci. 11:1359–1366.Google Scholar
  47. Mereu G, Lilliu V, Casula A, Vargiu PF, Diana M, Musa A, Gessa GL (1997) Spontaneous bursting activity of dopaminergic neurons in midbrain slices from immature rats: Role of N-methyl-D-aspartate receptors. Neurosci. 77:1029–1036.Google Scholar
  48. Nakao M, Gadsby DC (1989) [Na] and [K] dependence of the Na/K pump current-voltage relationship in guinea pig ventricular myocytes. J. Gen. Physiol. 94:539–565.Google Scholar
  49. Nedergaard S, Flatman JA, Engberg I (1993) Nifedipine-and ω-conotoxin-sensitive Ca2+ conductances in guinea-pig substantia nigra pars compacta neurons. J. Physiol. 466:727–747.Google Scholar
  50. Ocallaghan J, Jarolimek W, Lewen A, Misgeld U (1996) (-)-baclofen-induced and constitutively active inwardly rectifying potassium conductances in cultured rat midbrain neurons. Pflugers Arch. 433:49–57.Google Scholar
  51. Overton P, Clark D (1992) Iontophoretically administered drugs acting at the N-methyl-D-aspartate receptor to modulate burst firing in A9 dopamine neurons in the rat. Synapse 10:131–140.Google Scholar
  52. Ping HX, Shepard PD (1996) Apamin-sensitive Ca2+-activated K+ channels regulate pacemaker activity in nigral dopamine neurons. NeuroReport 7:809–814.Google Scholar
  53. Preston RJ, McCrea RA, Chang HT, Kitai ST (1981) Anatomy and physiology of substantia nigra and retrorubral neurons studied by extra-and intracellular recording and by horseradish peroxidase labeling. Neurosci. 6:331–344.Google Scholar
  54. Pytkowicz RM, ed. (1979) Activity Coefficients in Electrolyte Solutions. CRC Press, Boca Raton, FL.Google Scholar
  55. Ribak CE, Vaughn JE, Roberts E (1980) GABAergic nerve terminals decrease in the substantia nigra following hemitransections of the striatonigral and pallidonigral pathways. Brain Res. 192:413–420.Google Scholar
  56. Rinzel J, Ermentrout GB (1989) Analysis of neuronal excitability and oscillations. In: C Koch, I Segev, eds. Methods in Neuronal Modeling: From Synapses to Networks. MIT Press, Cambridge, MA. pp.135–169.Google Scholar
  57. Robledo P, Feger J (1990) Excitatory influence of rat subthalamic nucleus to substantia nigra pars reticulata and the pallidal complex: Electrophysiological data. Brain Res. 518:47–54.Google Scholar
  58. Sanghera MK, Trulson ME, German DC (1984) Electrophysiological properties of mouse dopamine neurons: In Vivo and in vitro studies. Neurosci. 12:793–801.Google Scholar
  59. Scarnati E, Proia A, Campana E, Pacitti C (1986) A microiontophoretic study on the nature of the putative synaptic neurotransmitter involved in the pedunculopontine-substantia nigra pars compacta excitatory pathway of the rat. Exp. Brain Res. 46:470–478.Google Scholar
  60. Schultz W, Romo R, Ljungberg T, Mirenowicz J, Hollerman JR, Dickinson A (1995) Reward-related signals carried by dopamine neurons. In JC Houk, JL Davis, DG Beiser, eds. Models of Information Processing in the Basal Ganglia, MIT Press, Cambridge, MA. ch. 12, pp. 233–248.Google Scholar
  61. Sesack SR, Pickel VM (1992) Prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area. J. Comp. Neurol. 320:145–160.Google Scholar
  62. Seutin V, Johnson SW, North RA (1993a) Apamin increasesNMDAinduced burst-firing of rat mesencephalic dopamine neurons. Brain Res. 630: 341–344.Google Scholar
  63. Seutin V, Johnson SW, North RA (1994) Effect of dopamine and baclofen on N-methyl-D-aspartate-induced burst firing in rat ventral tegmental neurons. Neurosci. 58:201–206.Google Scholar
  64. Seutin V, North RA, Johnson SW (1993b) Transmitter regulation of mesencephalic dopamine cells. In PW Kalivas, CD Barnes, eds. Limbic Motor Circuits and Neuropsychiatry. CRC Press, Boca Raton. ch. 3, pp. 89–100.Google Scholar
  65. Seutin V, Shen KZ, North RA, Johnson SW (1996) Sulfonylureasensitive potassium current evoked by sodium-loading in rat midbrain dopamine neurons. Neurosci. 71:709–719.Google Scholar
  66. Shepard PD (1993) The cellular basis of conditional bursting in mesencephalic dopamine-containing neurons. Schizophren. Res. 9:167.Google Scholar
  67. Shepard PD, Bunney BS (1988) Effects of apamin on the discharge properties of putative dopamine-containing neurons in vitro. Brain Res. 463:380–384.Google Scholar
  68. Silva NL, Pechura CM, Barker JL (1990) Postnatal rat nigral dopaminergic neurons exhibit five types of potassium conductances. J. Neurophysiol. 64:262–272.Google Scholar
  69. Smith Y, Bolam JP (1990) The output neurones and the dopaminergic neurones of the substantia nigra receive a GABA-containing input from the globus pallidus in the rat. J. Comp. Neurol. 296:47–64.Google Scholar
  70. Svensson TH, Tung CS (1989) Local cooling of pre-frontal cortex induces pacemaker-like firing of dopamine neurons in rat ventral tegmental area in vivo. Acta Physiol. Scand. 136:135–136.Google Scholar
  71. Tepper JM, Martin LP, Anderson DR (1995) GABAA receptormediated inhibition of rat substantia nigra dopaminergic neurons by pars reticulata projection neurons. J. Neurosci. 15:3092–3103.Google Scholar
  72. Tepper JM, Sawyer SF, Groves PM (1987) Electrophysiologically identified nigral dopaminergic neurons intracellularly labeled with HRP: Light-microscopic analysis. J. Neurosci. 7:2794–2806.Google Scholar
  73. Tong ZY, Overton PG, Clark D (1996) Stimulation of the prefrontal cortex in the rat induces patterns of activity in midbrain dopaminergic neurons which resemble natural burst events. Synapse 22:195–208.Google Scholar
  74. Walaas I, Fonnum F (1980) Biochemical evidence for gammaaminobutyrate containing fibers from the nucleus accumbens to the substantia nigra and ventral tegmental area in the rat. Neurosci. 5:63–72.Google Scholar
  75. Wang T, French ED (1993a) Electrophysiological evidence for the existence of NMDA receptors on rat ventral tegmental dopamine neurons. Synapse 13:270–277.Google Scholar
  76. Wang T, French ED (1993b) L-glutamate excitation of A10 dopamine neurons is preferentially mediated by activation of NMDA receptors: Electrophysiological studies in brain slices. Brain Res. 623:299–306.Google Scholar
  77. Wang T, O'Connor WT, Ungerstedt U, French ED (1994) N-Methyl-D-aspartic acid biphasically regulates the biochemical and electrophysiological response of A10 dopamine neurons in the ventral tegmental area: in vivo microdialysis and in vitro electrophysiological studies. Brain Res. 666:255–262.Google Scholar
  78. Wang XJ, Rinzel J (1995) Oscillatory and bursting properties of neurons. In: MA Arbib, ed. The Handbook of Brain Theory and Neural Networks. MIT Press, Cambridge, MA. pp. 686–691.Google Scholar
  79. Watts AE, Williams JT, Henderson G (1996) Baclofen inhibition of the hyperpolarization-activated cation current may be secondary to potassium current activation. J. Neurophysiol. 76:2262–2270.Google Scholar
  80. Wilson CJ, Young SJ, Groves PM (1977) Statistical properties of neuronal spike trains in the substantia nigra: Cell types and their interactions. Brain Res. 136:243–260.Google Scholar
  81. Wu HQ, Schwarcz R, Shepard PD (1994) Excitatory amino acidinduced excitation of dopamine-containing neurons in the rat substantia nigra: Modulation by kynurenic acid. Synapse 16:219–230.Google Scholar
  82. Wu YN, Cameron W, Johnson SW (1996) Effect of baclofen on NMDA-mediated synaptic responses in rat midbrain dopamine neuron in vitro. Soc. Neurosci. Abstr. 22:1294.Google Scholar
  83. Wu YN, Johnson SW (1996) Pharmacological characterization of inward current evoked by N-methyl-D-aspartate in dopamine neurons in the rat brain slice. J. Pharmacol. Exp. Ther. 279:1–7.Google Scholar
  84. Yung WH, Hausser MA, Jack JJB (1991) Electrophysiology of dopaminergic and nondopaminergic neurones of the guinea-pig substantia nigra pars compacta in vitro. J. Physiol. 436:643–667.Google Scholar
  85. Zhang J, Chiodo LA, Freeman AS (1994) Influence of excitatory amino acid receptor subtypes on the electrophysiological activity of dopaminergic and nondopaminergic neurons in rat substantia nigra. J. Pharmacol. Exp. Ther. 269:313–321.Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • C.C. Canavier
    • 1
  1. 1.Department of PsychologyUniversity of New OrleansNew Orleans

Personalised recommendations