Journal of Computational Neuroscience

, Volume 24, Issue 3, pp 314–329 | Cite as

A model for modulation of neuronal synchronization by D4 dopamine receptor-mediated phospholipid methylation

  • Anna Y. Kuznetsova
  • Richard C. DethEmail author


We describe a new molecular mechanism of dopamine-induced membrane protein modulation that can tune neuronal oscillation frequency to attention-related gamma rhythm. This mechanism is based on the unique ability of D4 dopamine receptors (D4R) to carry out phospholipid methylation (PLM) that may affect the kinetics of ion channels. We show that by deceasing the inertia of the delayed rectifier potassium channel, a transition to 40 Hz oscillations can be achieved. Decreased potassium channel inertia shortens spike duration and decreases the interspike interval via its influence on the calcium-dependent potassium current. This mechanism leads to a transition to attention-related gamma oscillations in a pyramidal cell-interneuron network. The higher frequency and better synchronization is observed with PLM affecting pyramidal neurons only, and recurrent excitation between pyramidal neurons is important for synchronization. Thus dopamine-stimulated methylation of membrane phospholipids may be an important mechanism for modulating firing activity, while impaired methylation can contribute to disorders of attention.


Gamma oscillations Potassium channel Attention Autism Schizophrenia Membrane fluidity Attention-deficit hyperactivity disorder 


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  1. Abdolmaleky, H. M., Cheng, K. H., Faraone, S. V., Wilcox, M., Glatt, S. J., Gao, F., et al. (2006). Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Human Molecular Genetics, 15(21), 3132–3145.PubMedGoogle Scholar
  2. Aguirre-Samudio, A. J., & Nicolini, H. (2005). DRD4 polymorphism and the association with mental disorders. Revista de Investigacion Clinica, 57(1), 65–75 (article in Spanish).PubMedGoogle Scholar
  3. Ahveninen, J., Kahkonen, S., Tiitinen H., Pekkonen E., Huttunen J., Kaakkola S., et al. (2000). Suppression of transient 40-Hz auditory response by haloperidol suggests modulation of human selective attention by dopamine D2 receptors. Neuroscience Letters, 292, 29–32.PubMedGoogle Scholar
  4. Alfimova, M., Golimbet, V., Gritsenko, I., Lezheiko, T., Abramova, L., Strel’tsova, M., et al. (2006). Dopamine system genes interaction and neurocognitive traits in patients with schizophrenia, their relatives and healthy controls from general population. Zhurnal Nevrologii i Psikhiatrii Imeni S S Korsakova, 106, 57–63 (article in Russian).PubMedGoogle Scholar
  5. Avale, M. E., Falzone, T. L., Gelman, D. M., Low, M. J., Grandy, D. K., & Rubinstein, M. (2004). The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder. Molecular Psychiatry, 9(7), 718–726.PubMedGoogle Scholar
  6. Axelrod, J., & Hirata, F. (1981). Phospholipid methylation and membrane function. Annals of the New York Academy of Sciences, 373(1), 51–53.PubMedGoogle Scholar
  7. Benjamin, J., Li, L., Patterson, C., Greenberg, B. D., Murphy, D. L., & Hamer, D. H. (1996). Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nature Genetics, 12, 81–84.PubMedGoogle Scholar
  8. Benjamin, J., Osher, Y., Kotler, M., Gritsenko, I., Nemanov, L., Belmaker, R. H., et al. (2000). Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: Dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT). Molecular Psychiatry, 5, 96–100.PubMedGoogle Scholar
  9. Bezanilla, F. (2000). The voltage sensor in voltage-dependent ion channels. Physiological Reviews, 80, 555–592.PubMedGoogle Scholar
  10. Bond, P. J., & Sansom, M. S. (2007). Bilayer deformation by the Kv channel voltage sensor domain revealed by self-assembly simulations. Proceedings of the National Academy of Sciences of the United States of America, 104, 2631–2636.PubMedGoogle Scholar
  11. Borgers, C., Epstein, S., & Kopell, N. (2005). Background gamma rhythmicity and attention in cortical local circuits: A computational study. Proceedings of the National Academy of Sciences of the United States of America, 19, 7002–7007.Google Scholar
  12. Borisyuk, R., Denham, M., Hoppensteadt, F., Kazanovich, Y., & Vinogradova, O. (2001). Oscillatory model of novelty detection. Network, 12, 1–20.PubMedGoogle Scholar
  13. Brookes, K., Xu, X., Chen, W., Zhou, K., Neale, B., Lowe, N., et al. (2006). The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: Association signals in DRD4, DAT1 and 16 other genes. Molecular Psychiatry, 11, 934–953.PubMedGoogle Scholar
  14. Buia, C., & Tiesinga, P. (2006). Attentional modulation of firing rate and synchrony in a model cortical network. Journal of Computational Neuroscience, 20, 247–264.PubMedGoogle Scholar
  15. Burgess, J. R., Stevens, L., Zhang, W., & Peck, L. (2000). Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. American Journal of Clinical Nutrition, 71, 327S–330S.PubMedGoogle Scholar
  16. Cannon, B., Hermansson, M., Gyorke, S., Somerharju, P., Virtanen, J. A., & Cheng, K. H. (2003). Regulation of calcium channel activity by lipid domain formation in planar lipid bilayers. Biophysical Journal, 85, 933–942.PubMedCrossRefGoogle Scholar
  17. Cascio, M. (2005). Connexins and their environment: Effects of lipids composition on ion channels. Biochimica et Biophysica Acta, 1711, 142–153.PubMedGoogle Scholar
  18. Chang, H. M., Reitstetter, R., & Gruener, R. (1995a). Lipid–ion channel interactions: Increasing phospholipid headgroup size but not ordering acyl chains alters reconstituted channel behavior. Journal of Membrane Biology, 145, 13–19.Google Scholar
  19. Chang, H. M., Reitstetter, R., Mason, R. P., & Gruener, R. (1995b). Attenuation of channel kinetics and conductance by cholesterol: An interpretation using structural stress as a unifying concept. Journal of Membrane Biology, 143, 51–63.Google Scholar
  20. Chrobak, J. J., & Buzsaki, G. (1998). Gamma oscillations in the entorhinal cortex of the freely behaving rat. Journal of Neuroscience, 18, 388–398.PubMedGoogle Scholar
  21. Clarke, A. L., Petrou, S., Walsh, J. V. J., & Singer, J. J. (2002). Modulation of BK(Ca) channel activity by fatty acids: Structural requirements and mechanism of action. American Journal of Physiology Cell Physiology, 283, C1441–1453.PubMedGoogle Scholar
  22. De La Garza, R., & Madras, B. K. (2000). [(3)H]PNU-101958, a D(4) dopamine receptor probe, accumulates in prefrontal cortex and hippocampus of non-human primate brain. Synapse, 37, 232–244.PubMedGoogle Scholar
  23. Demiralp, T., Herrmann, C. S., Erdal, M. E., Ergenoglu, T., Keskin, Y. H., Ergen, M., et al. (2007). DRD4 and DAT1 polymorphisms modulate human gamma band responses. Cerebral Cortex, 17(5):1007–1019. doi: 10.1093/cercor/bhl011.Google Scholar
  24. Deol, S., Bond, P., & Sansom, M. (2004). Lipid–protein interactions of integral membrane proteins: A comparative simulation study. Biophysical Journal, 87, 3737–3749.PubMedGoogle Scholar
  25. Deth, R. C. (2003). Molecular origins of human attention: The dopamine-folate connection (pp. 2–246). Kluwer, Boston, MA.Google Scholar
  26. Deth, R. C., Kuznetsova, A., & Waly, M. (2004). Attention-related signaling activities of the D4 dopamine receptor. In M. I. Posner (Ed.), Cognitive neuroscience of attention (pp. 269–282). Guilford Publications, NY.Google Scholar
  27. Deth, R. C., Mehta, S., Tan, W., Liu, Y. F., & Marshall, J. (1999). D4 dopamine receptors co-localize with the synaptic scaffolding protein SAP-97 and glutamate receptors in rat brain extracts. Society for Neuroscience Abstract, 25, 2214.Google Scholar
  28. Ding, Y. C., Chi, H. C., Grady, D. L., Morishima, A., Kidd, J. R., Kidd, K. K., et al. (2002). Evidence of positive selection acting at the human dopamine receptor D4 gene locus. Proceedings of the National Academy of Sciences of the United States of America, 99, 309–314.PubMedGoogle Scholar
  29. Dong, Y., & White, F. J. (2003). Dopamine D1-class receptors selectively modulate a slowly inactivating potassium current in rat medial prefrontal cortex pyramidal neurons. Journal of Neuroscience, 23(7), 2686–2695.PubMedGoogle Scholar
  30. Dzirasa, K., Ribeiro, S., Costa, R., Santos, L. M., Lin, S. C., Grosmark, A., et al. (2006). Dopaminergic control of sleep–wake states. Journal of Neuroscience, 26(41), 10577–10589.PubMedGoogle Scholar
  31. Ebstein, R. P., Novick, O., Umansky, R., Priel, B., Osher, Y., Blaine, D., et al. (1996). Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking. Nature Genetics, 12, 78–80.PubMedGoogle Scholar
  32. Engel, A. K. U., Moll, C. K., Fried, I., & Ojemann, G. A. (2005). Invasive recordings from the human brain: Clinical insights and beyond. Nature Reviews Neuroscience, 6(1), 35–47.PubMedGoogle Scholar
  33. Ermentrout, B. (2002). Simulating, analyzing, and animating dynamical systems: A guide to xppaut for researchers and students. Society for Industrial and Applied Mathematics, Philadelphia, PA.Google Scholar
  34. Fell, J., Fernandez, G., Klaver, P., Elger, C. E., & Fries, P. (2003). Is synchronized neuronal gamma activity relevant for selective attention? Brain Research, 42, 265–272.Google Scholar
  35. Forlenza, O. V., Schaeffer, E. L., & Gattaz, W. F. (2007). The role of phospholipase A2 in neuronal homeostasis and memory formation: Implications for the pathogenesis of Alzheimer’s disease. Journal of Neural Transmission, 114, 231–238.PubMedGoogle Scholar
  36. Freites, J. A., Tobias, D. J., von Heijne, G., & White, S. H. (2005). Interface connections of a transmembrane voltage sensor. Proceedings of the National Academy of Sciences of the United States of America, 102, 15059–15064.PubMedGoogle Scholar
  37. Fries, P., Reynolds, J. H., Rorie, A. E., & Desimone, R. (2001). Modulation of oscillatory neuronal synchronization by selective visual attention. Science, 291, 1560–1563.PubMedGoogle Scholar
  38. Gandhi, C. R., & Ross, D. H. (1989). Influence of ethanol on calcium, inositol phospholipids and intracellular signaling mechanisms. Experientia, 45, 407–413.PubMedGoogle Scholar
  39. Gao, W. J. (2007). Acute clozapine suppresses synchronized pyramidal synaptic network activity by increasing inhibition in the ferret prefrontal cortex. Journal of Neurophysiology, 97(2), 1196–1208.PubMedGoogle Scholar
  40. Golimbet, V., Gritsenko, I., Alfimova, M., Lezheiko, T., Abramova, L., Barkhatova, A., et al. (2005a). Dopamine receptor DRD4 gene polymorphism and its association with schizophrenia spectrum disorders and personality traits in patients. Zhurnal Nevrologii i Psikhiatrii Imeni S S Korsakova, 105, 42–47 (article in Russian).Google Scholar
  41. Golimbet, V., Lebedeva, I., Gritsenko, I., Korovaitseva, G., Alfimova, M., Lezheiko, T., et al. (2005b). A study of some genes related to serotoninergic and dopaminergic systems and auditory evoked-potentials (P300) in patients with schizophrenia and spectrum disorders and their first-degree relatives. Zhurnal Nevrologii i Psikhiatrii Imeni S S Korsakova, 105, 35–41 (article in Russian).Google Scholar
  42. Gorospe, W. C., & Conn, P. M. (1988). Restoration of the LH secretory response in desensitized gonadotropes. Molecular and Cellular Endocrinology, 59, 101–110.PubMedGoogle Scholar
  43. Grayson, D. R., Chen, Y., Costa, E., Dong, E., Guidotti, A., Kundakovic, M., et al. (2006). The human reelin gene: Transcription factors (+), repressors (–) and the methylation switch (+/–) in schizophrenia. Pharmacology & Therapeutics, 111(1), 272–286.Google Scholar
  44. Gruhn, M., Guckenheimer, J., Land, B., & Harris-Warrick, R. M. (2005). Dopamine modulation of two delayed rectifier potassium currents in a small neural network. Journal of Neurophysiology, 94, 2888–2900.PubMedGoogle Scholar
  45. Guan, Z. Z., Wang, Y. N., Xiao, K. Q., Hu, P. S., & Liu, J. L. (1999). Activity of phosphatidylethanolamine-N-methyltransferase in brain affected by Alzheimer’s disease. Neurochemistry International, 34, 41–47.PubMedGoogle Scholar
  46. Herrmann, C. S., & Demiralp, T. (2005). Human EEG gamma oscillations in neuropsychiatric disorders. Clinical Neurophysiology, 116, 2719–2733.PubMedGoogle Scholar
  47. Hirata, F., Strittmatter, W. J., & Axelrod, J. (1979). Beta-adrenergic receptor agonists increase phospholipid methylation, membrane fluidity, and beta-adrenergic receptor-adenylate cyclese coupling. Proceedings of the National Academy of Sciences of the United States of America, 76, 368–372.PubMedGoogle Scholar
  48. Hirata, F., & Axelrod, J. (1980). Phospholipid methylation and biological signal transmission. Science, 209(4461), 1082–90.PubMedGoogle Scholar
  49. Hirata, F., Tallman, J. F., Henneberry, R. C., Mallorga, P., Strittmatter, W. J., & Axelrod, J. (1981). Phospholipid methylation: A possible mechanism of signal transduction across biomembranes. Progress in Clinical and Biological Research, 63, 383–388.PubMedGoogle Scholar
  50. Hitzemann, R. J., & Harris, R. A. (1984). Developmental changes in synaptic membrane fluidity: A comparison of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). Brain Research, 316, 113–20.PubMedGoogle Scholar
  51. Hitzemann, R., Hirschowitz, J., Panini, A., Mark, C., & Garver, D. (1984). Membranes, methylation and lithium responsive psychoses. Nutrition & Health, 3(3), 153–162.Google Scholar
  52. Hitzemann, R., Mark, C., Hirschowitz, J., & Garver, D. (1985). Characteristics of phospholipid methylation in human erythrocyte ghosts: Relationship(s) to the psychoses and affective disorders. Biological Psychiatry, 20, 397–407.PubMedGoogle Scholar
  53. Horrocks, L. A., & Farooqui, A. A. (2004). Docosahexaenoic acid in the diet: Its importance in maintenance and restoration of neural membrane function. Prostaglandins, Leukotrienes and Essential Fatty Acids, 70, 361–72.Google Scholar
  54. Inanobe, A., Yoshimoto, Y., Horio, Y., Morishige, K. J., Hibino, H., Matsumoto, S., et al. (1999). Characterization of G-protein-gated K + channels composed of Kir3.2 subunits in dopaminergic neurons of the substantia nigra. Journal of Neuroscience, 19, 1006–1017.PubMedGoogle Scholar
  55. James, S. J., Cutler, P., Melnyk, S., Jernigan, L. S. J., Gaylor, D. W., & Neubrander, J. A. (2004). Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. American Journal of Clinical Nutrition, 80, 1611–1617.PubMedGoogle Scholar
  56. Jiang, Y., Lee, A., Chen, J., Cadene, M., Chait, B. T., & MacKinnon, R. (2002). Crystal structure and mechanism of a calcium-gated potassium channel. Nature, 417(6888), 515–522.PubMedGoogle Scholar
  57. Jiang, Y., Lee, A., Chen, J., Ruta, V., Cadene, M., Chait, B. T., et al. (2003a). X-ray structure of a voltage-dependent K + channel. Nature, 423, 33–41.Google Scholar
  58. Jiang, Y., Ruta, V., Chen, J., Lee, A., & MacKinnon, R. (2003b). The principle of gating charge movement in a voltage-dependent K + channel. Nature, 423, 42–48.Google Scholar
  59. Just, M. A., Cherkassky, V. L., Keller, T. A., & Minshew, N. J. (2004). Cortical activation and synchronization during sentence comprehension in high-functioning autism: Evidence of underconnectivity. Brain, 127, 1811–1821.PubMedGoogle Scholar
  60. Kahkonen, S., & Ahveninen, J. (2002). Combination of magneto- and electroencephalography in studies of monoamine modulation on attention. Methods and Findings in Experimental and Clinical Pharmacology, 24(Suppl C), 27–34.PubMedGoogle Scholar
  61. Kahkonen, S., Ahveninen, J., Jaaskelainen, I. P., Kaakkola, S., Naatanen, R., Huttunen, J., et al. (2001). Effects of haloperidol on selective attention: A combined whole-head MEG and high-resolution EEG study. Neuropsychopharmacology, 25, 498–504.PubMedGoogle Scholar
  62. Kelsoe, J. R. J., Tolbert, L. C., Crews, E. L., & Smythies, J. R. (1982). Kinetic evidence for decreased methionine adenosyltransferase activity in erythrocytes from schizophrenics. Journal of Neuroscience Research, 8, 99–103.PubMedGoogle Scholar
  63. Kim, E., & Sheng, M. (1996). Differential K + channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases. Neuropharmacology, 35, 993–1000.PubMedGoogle Scholar
  64. Kopell, N., Ermentrout, G. B., Whittington, M. A., & Traub, R. D. (2000). Gamma rhythms and beta rhythms have different synchronization properties. Proceedings of the National Academy of Sciences of the United States of America, 97, 1867–1872.PubMedGoogle Scholar
  65. Kwon, J. S., O’Donnell, B. F., Wallenstein, G. V., Greene, R. W., Hirayasu, Y., Nestor, P. G., et al. (1999). Gamma frequency-range abnormalities to auditory stimulation in schizophrenia. Archives of General Psychiatry, 56, 1001–1005.PubMedGoogle Scholar
  66. LaHoste, G. J., Swanson, J. M., Wigal, S. B., Glabe, C., Wigal, T., King, N., et al. (1996). Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Molecular Psychiatry, 1, 121–124.PubMedGoogle Scholar
  67. Lanau, F., Zenner, M. T., Civelli, O., & Hartman, D. S. (1997). Epinephrine and norepinephrine act as potent agonists at the recombinant human dopamine D4 receptor. Journal of Neurochemistry, 68, 804–812.PubMedCrossRefGoogle Scholar
  68. Laumonnier, F., Roger, S., Guerin, P., Molinari, F., M′rad, R., Cahard, D., et al. (2006). Association of a functional deficit of the BK Ca channel, a synaptic regulator of neuronal excitability, with autism and mental retardation. American Journal of Psychiatry, 163, 1622–1629.PubMedGoogle Scholar
  69. Lavine, N., Ethier, N., Oak, J. N., Pei, L., Liu, F., Trieu, P., et al. (2002). G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase. Journal of Biological Chemistry, 277, 46010–46019.PubMedGoogle Scholar
  70. Laviolette, S. R., Lipski, W. J., & Grace, A. A. (2005). A subpopulation of neurons in the medial prefrontal cortex encodes emotional learning with burst and frequency codes through a dopamine D4 receptor-dependent basolateral amygdala input. Journal of Neuroscience, 25(26), 6066–6075.PubMedGoogle Scholar
  71. Lebel, C. P., & Schatz, R. A. (1990). Altered synaptosomal phospholipid metabolism after toluene: Possible relationship with membrane fluidity, Na+, K+-adenosine triphosphatase and phospholipid methylation. Journal of Pharmacology and Experimental Therapeutics, 253, 1189–1197.PubMedGoogle Scholar
  72. Lee, A. G. (2002). A calcium pump made visible. Current Opinion in Structural Biology, 12(4), 547–554.PubMedGoogle Scholar
  73. Lee, A. G. (2003). Lipid–protein interactions in biological membranes: A structural perspective. Biochimica et Biophysica Acta, 1612, 1–40.PubMedGoogle Scholar
  74. Lee, K. J. (2006). Energetics of rotational gating mechanisms of an ion channel induced by membrane deformation. Physical Review E, 73, 021909.Google Scholar
  75. Lee, S. Y., Lee, A., Chen, J., & MacKinnon, R. (2005). Structure of the KvAP voltage-dependent K channel and its dependence on the lipid membrane. Proceedings of the National Academy of Sciences of the United States of America, 102, 15441–15446.PubMedGoogle Scholar
  76. Lewine, J. D., Andrews, R., Chez, M., Patil, A. A., Devinsky, O., Smith, M., et al. (1999). Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders. Pediatrics, 104(3 Pt 1), 405–418.PubMedGoogle Scholar
  77. Lisman, J. E., & Idiart, M. A. (1995). Storage of 7 ± 2 short-term memories in oscillatory subcycles. Science, 267, 1512–1515.PubMedGoogle Scholar
  78. Lisman, J. E., & Otmakhova, N. A. (2001). Storage, recall, and novelty detection of sequences by the hippocampus: Elaborating on the SOCRATIC model to account for normal and aberrant effects of dopamine. Hippocampus, 11, 551–568.PubMedGoogle Scholar
  79. Liu, L. X., Burgess, L. H., Gonzalez, A. M., Sibley, D. R., & Chiodo, L. A. (1999). D2S, D2L, D3 and D4 dopamine receptors couple to a voltage-dependent potassium current in N18TG2 x mesencephalon hybrid cell (MES-23.5) via distinct G proteins. Synapse, 31, 108–118.PubMedGoogle Scholar
  80. Long, S. B., Campbell, E. B., & Mackinnon, R. (2005). Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science, 309(5736), 897–903.PubMedGoogle Scholar
  81. Lundbaek, J. A., Birn, P., Hansen, A. J., Sogaard, R., Nielsen, C., Girshman, J., et al. (2004). Regulation of sodium channel function by bilayer elasticity: The importance of hydrophobic coupling. Effects of micelle-forming amphiphiles and cholesterol. Journal of General Physiology, 123, 599–621.PubMedGoogle Scholar
  82. McAdams, C. J., & Maunsell, J. H. (1999). Effects of attention on orientation-tuning functions of single neurons in macaque cortical area V4. Journal of Neuroscience, 19, 431–441.PubMedGoogle Scholar
  83. McCaddon, A. (2006). Homocysteine and cognition—A historical perspective. Journal of Alzheimer’s Disease, 9(4), 361–380.PubMedGoogle Scholar
  84. McIntosh, T. J., & Simon, S. A. (2006). Roles of bilayer material properties in function and distribution of membrane proteins. Annual Review of Biophysics and Biomolecular Structure, 35, 177–198.PubMedGoogle Scholar
  85. Meininger, V., Phan, T., Camelin, J. C., Gauthier, A., Mizoule, J., Benavides, J., et al. (1984). Methylation of erythrocyte membrane phospholipids: Correlation with membrane viscosity. Study of normal and parkinsonian subjects. Revue Neurologique (Paris), 140, 488–492.Google Scholar
  86. Miller, C. (2000). An overview of the potassium channel family. Genome Biology, 1(4), REVIEWS0004.Google Scholar
  87. Morere, D. A., Alarcon, R. D., Monti, J. A., Walter-Ryan, W. G., Bancroft, A. J., Smythies, J. R., et al. (1986). Medication effects on one-carbon metabolism in schizophrenia, mania, and major depression. Journal of Clinical Psychopharmacology, 6, 155–161.PubMedGoogle Scholar
  88. Mrzijak, L., Bergson, C., Pappy, M., Huff, R., Levenson, R., & Goldman-Rakic, P. S. (1996). Localization of dopamine D4 receptors in GABAergic neurons of the primate brain. Nature, 381, 245–248.Google Scholar
  89. Nishizawa, M., & Nishizawa, K. (2006). Interaction between K channel gate modifier hanatoxin and lipid bilayer membranes analyzed by molecular dynamics simulation. European Biophysics Journal, 35, 373–381.PubMedGoogle Scholar
  90. Oak, J. N., Oldenhof, J., & Van Tol, H. H. (2000). The dopamine D(4) receptor: One decade of research. European Journal of Pharmacology, 405, 303–327.PubMedGoogle Scholar
  91. Oliver, D., Lien, C. C., Soom, M., Baukrowitz, T., Jonas, P., & Fakler, B. (2004). Functional conversation between A-type and delayed rectifier K+ channels by membrane lipids. Science, 304, 263–274.Google Scholar
  92. Otmakhova, N. A., & Lisman, J. E. (1999). Dopamine selectively inhibits the direct cortical pathway to the CA1 hippocampal region. Journal of Neuroscience, 19, 1437–1445.PubMedGoogle Scholar
  93. Perez, M. F., White, F. J., & Hu, X. T. (2006). Dopamine D2 receptor modulation of K+ channel activity regulates excitability of nucleus accumbens neurons at different membrane potentials. Journal of Neurophysiology, 96, 2217–2228. doi: 10.1152/jn.00254.2006.Google Scholar
  94. Pillai, G., Brown, N. A., McAllister, G., Milligan, G., & Seabrook, G. R. (1998). Human D2 and D4 dopamine receptors couple through betagamma G-protein subunits to inwardly rectifying K+ channels (GIRK1) in a Xenopus oocyte expression system: Selective antagonism by L-741,626 and L-745,870 respectively. Neuropharmacology, 37, 983–987.PubMedGoogle Scholar
  95. Reynolds, J. H., Pasternak, T., & Desimone, R. (2000). Attention increases sensitivity of V4 neurons. Neuron, 26, 703–714.PubMedGoogle Scholar
  96. Rivera, A., Trias, S., Penafiel, A., Angel Narvaez, J., Diaz-Cabiale, Z., Moratalla, R., et al. (2003). Expression of D4 dopamine receptors in striatonigral and striatopallidal neurons in the rat striatum. Brain Research, 989, 35–41.PubMedGoogle Scholar
  97. Robbe, D., Montgomery, S. M., Thome, A., Rueda-Orozco, P. E., McNaughton, B. L., & Buzsaki, G. (2006). Cannabinoids reveal importance of spike timing coordination in hippocampal function. Nature Neuroscience, 9, 1526–1533.PubMedGoogle Scholar
  98. Ross, S. B. (1991). Synaptic concentration of dopamine in the mouse striatum in relationship to the kinetic properties of the dopamine receptors and uptake mechanism. Journal of Neurochemistry, 56, 22–29.PubMedGoogle Scholar
  99. Sanyal, S., & Van Tol, H. H. (1997). Review the role of dopamine D4 receptors in schizophrenia and antipsychotic action. Journal of Psychiatric Research, 31, 219–232.PubMedGoogle Scholar
  100. Schaeffer, E. L., Bassi, F. Jr., & Gattaz, W. F. (2005). Inhibition of phospholipase A2 activity reduces membrane fluidity in rat hippocampus. Journal of Neural Transmission, 112, 641–647.PubMedGoogle Scholar
  101. Schaeffer, E. L., & Gattaz, W. F. (2007). Requirement of hippocampal phospholipase A2 activity for long-term memory retrieval in rats. Journal of Neural Transmission, 114, 379–385PubMedGoogle Scholar
  102. Schmidt, D., Jiang, Q., & MacKinnon, R. (2006). Phospholipids and the origin of cationic gating charges in voltage sensors. Nature, 444, 775–779.PubMedGoogle Scholar
  103. Seeman, P., Guan, H. C., & Van Tol, H. H. (1993). Dopamine receptors elevated in schizophrenia. Nature, 365, 441–445.PubMedGoogle Scholar
  104. Selley, M. L. (2006). A metabolic link between S-adeno-sylhomocysteine and polyunsaturated fatty acid metabolism in Alzheimer’s disease. Neurobiology of Aging, 24, 903–907. doi: 10.1016/j.neurobiolaging.2006.08.003.
  105. Sharma, A., Kramer, M. L., Wick, P. F., Liu, D., Chari, S., Shim, S., et al. (1999). D4 dopamine receptor-mediated phospholipid methylation and its implications for mental illnesses such as schizophrenia. Molecular Psychiatry, 4, 235–246.PubMedGoogle Scholar
  106. Spenser, K. M., Nestor, P. G., Niznikiewicz, M. A., Salisbury, D. F., Shenton, M. E., & McCarley, R. W. (2003). Abnormal neural synchrony in schizophrenia. Journal of Neuroscience, 23(19), 7407–7411.Google Scholar
  107. Sperotto, M. M., May, S., & Baumgaertner, A. (2006). Modeling of proteins in membranes. Chemistry and Physics of Lipids, 141, 2–29.PubMedGoogle Scholar
  108. Strittmatter, W. J., Hirata, F., & Axelrod, J. (1979). Increased Ca2+-ATPase activity associated with methylation of phospholipids in human erythrocytes. Biochemical and Biophysical Research Communications, 88, 147–153.PubMedGoogle Scholar
  109. Strittmatter, W. J., Hirata, F., & Axelrod, J. (1981). Regulation of the beta-adrenergic receptor by methylation of membrane phospholipids. Advances in Cyclic Nucleotide Research, 14, 83–91.PubMedGoogle Scholar
  110. Swanson, J., Oosterlaan, J., Murias, M., Schuck, S., Flodman, P., Spence, M. A., et al. (2000). Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention. Proceedings of the National Academy of Sciences of the United States of America, 97, 4754–4759.PubMedGoogle Scholar
  111. Swanson, J. M., Kinsbourne, M., Nigg, J., Lanphear, B., Stefanatos, G. A., Volkow, N., et al. (2007). Etiologic subtypes of attention-deficit/hyperactivity disorder: Brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychology Review, 17, 39–59.PubMedGoogle Scholar
  112. Tiesinga, P. H. E., Fellous, J. M., Salinas, E., Jose, J. V., & Sejnowski, T. J. (2004). Synchronization as a mechanism for attentional gain modulation. Neurocomputing, 58–60, 641–646.PubMedGoogle Scholar
  113. Tiesinga, P. H. E., & Sejnowsk, T. J. (2004). Rapid temporal modulation of synchrony by competition in cortical interneuron networks. Neural Computation, 16, 251–275.PubMedGoogle Scholar
  114. Tiffany, A. M., Manganas, L. N., Kim, E., Hsueh, Y. P., Sheng, M., & Trimmer, J. S. (2000). PSD-95 and SAP97 exhibit distinct mechanisms for regulating K+ channel surface expression and clustering. Journal of Cell Biology, 148, 147–158.PubMedGoogle Scholar
  115. Tillman, T. S., & Cascio, M. (2003). Effects of membrane lipids on ion channel structure and function. Cell Biochemistry and Biophysics, 38, 161–190.PubMedGoogle Scholar
  116. Traub, R., Contreras, D., Cunningham, M., Murray, H., LeBeau, F., Roopun, A., et al. (2005). Single-column thalamocortical network model exhibiting gamma oscillations, sleep spindles, and epileptogenic bursts. Journal of Neurophysiology, 93, 1829–30.Google Scholar
  117. Traub, R., Whittington, M., Buhl, E., Jefferys, J., & Faulkner, H. (1999). On the mechanism of the gamma to beta frequency shift in neuronal oscillations induced in rat hippocampal slices by tetanic stimulation. Journal of Neuroscience, 19, 1088–105.PubMedGoogle Scholar
  118. Uhlhaas, P. J., & Singer, W. (2006). Neural synchrony in brain disorders: Relevance for cognitive dysfunctions and pathophysiology. Neuron, 52, 155–168.PubMedGoogle Scholar
  119. Van Petegem, F., Clark, K. A., Chatelain, F. C., & Minor, D. L. J. (2004). Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain. Nature, 429(6992), 671–675.PubMedGoogle Scholar
  120. Venturoli, M., Smit, B., & Sperotto, M. (2005). Simulation studies of protein-induced bilayer deformations, and lipid-induced protein tilting, on a mesoscopic model for lipid bilayers with embedded proteins. Biophysical Journal, 88, 1778–1798.PubMedGoogle Scholar
  121. Volkow, N. D., Wang, G. J., Fowler, J. S., & Ding, Y. S. (2005). Imaging the effects of methylphenidate on brain dopamine: New model on its therapeutic actions for attention-deficit/hyperactivity disorder. Biological Psychiatry, 57(11), 1410–1415.PubMedGoogle Scholar
  122. Wedemeyer, C., Goutman, J. D., Avale, M. E., Franchini, L. F., Rubinstein, M., & Calvo, D. J. (2007). Functional activation by central monoamines of human dopamine D4 receptor polymorphic variants coupled to GIRK channels in Xenopus oocytes. European Journal of Pharmaca, 562, 165–173.Google Scholar
  123. Wedzony, K., Chocyk, A., Mackowiak, M., Fijal, K., & Czyrak, A. (2000). Cortical localization of dopamine D4 receptors in the rat brain-immunocytochemical study. Journal of Physiology and Pharmacology, 51, 205–221.PubMedGoogle Scholar
  124. Werner, P., Hussy, N., Buell, G., Jones, K. A., & North, R. A. (1996). D2, D3, and D4 dopamine receptors couple to G protein-regulated potassium channels in Xenopus oocytes. Molecular Pharmacology, 49, 656–661.PubMedGoogle Scholar
  125. Wheless, J. W., Simos, P. G., & Butler, I. J. (2002). Language dysfunction in epileptic conditions. Seminars in Pediatric Neurology, 9, 218–228.PubMedGoogle Scholar
  126. Wilson, H. R. (1999). Simplified dynamics of human and mammalian neocortical neurons. Journal of Theoretical Biology, 200, 375–388.PubMedGoogle Scholar
  127. Wilson, T. W., Rojas, D. C., Reite, M. L., Teale, P. D., & Rogers, S. J. (2007). Children and adolescents with autism exhibit reduced MEG steady-state gamma responses. Biological Psychiatry, 62(3), 192–197.PubMedGoogle Scholar
  128. Womelsdorf, T., & Fries, P. (2007). The role of neuronal synchronization in selective attention. Current Opinion in Neurobiology, 17(2), 154–160.PubMedGoogle Scholar
  129. Yang, C. R., & Seamans, J. K. (1996). Dopamine D1 receptor actions in layers V–VI rat prefrontal cortex neurons in vitro: Modulation of dendritic-somatic signal integration. Journal of Neuroscience, 16, 1922–1935.PubMedGoogle Scholar
  130. Yordanova, J., Banaschewski, T., Kolev, V., Woerner, W., & Rothenberger, A. (2001). Abnormal early stages of task stimulus processing in children with attention-deficit hyperactivity disorder-evidence from event-related gamma oscillations. Clinical Neurophysiology, 112, 1096–1108.PubMedGoogle Scholar
  131. Zhao, R., Chen, Y., Tan, W., Waly, M., Sharma, A., Stover, P., et al. (2001). Relationship between dopamine-stimulated phospholipid methylation and the single-carbon folate pathway. Journal of Neurochemistry, 78, 788–796.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Neuroscience Center of ExcellenceLouisiana State University Health Sciences CenterNew OrleansUSA
  2. 2.Department of Nonlinear ProcessesSaratov State UniversitySaratovRussia
  3. 3.Department of Pharmaceutical SciencesNortheastern UniversityBostonUSA

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