Journal of Neural Transmission

, Volume 116, Issue 8, pp 1037–1052 | Cite as

Implications of the ‘Energide’ concept for communication and information handling in the central nervous system

  • L. F. Agnati
  • K. Fuxe
  • F. Baluška
  • D. Guidolin
Basic Neurosciences, Genetics and Immunology - Review Article


Recently a revision of the cell theory has been proposed, which has several implications both for physiology and pathology. This revision is founded on adapting the old Julius von Sach’s proposal (1892) of the Energide as the fundamental universal unit of eukaryotic life. This view maintains that, in most instances, the living unit is the symbiotic assemblage of the cell periphery complex organized around the plasma membrane, some peripheral semi-autonomous cytosol organelles (as mitochondria and plastids, which may be or not be present), and of the Energide (formed by the nucleus, microtubules, and other satellite structures). A fundamental aspect is the proposal that the Energide plays a pivotal and organizing role of the entire symbiotic assemblage (see Appendix 1). The present paper discusses how the Energide paradigm implies a revision of the concept of the internal milieu. As a matter of fact, the Energide interacts with the cytoplasm that, in turn, interacts with the interstitial fluid, and hence with the medium that has been, classically, known as the internal milieu. Some implications of this aspect have been also presented with the help of a computational model in a mathematical Appendix 2 to the paper. Finally, relevances of the Energide concept for the information handling in the central nervous system are discussed especially in relation to the inter-Energide exchange of information.


Lipid Raft Interstitial Fluid Neuronal Circuit Local Circuit Metabolic Unit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abbott LF, Regehr WG (2004) Synaptic computation. Nature 431:796–803PubMedCrossRefGoogle Scholar
  2. Agnati LF (2001) Fisiologia dell’ Apparato Renale. Athena Audiovisuals, ModenaGoogle Scholar
  3. Agnati LF, Fuxe K (1984) New concepts on the structure of the neuronal networks: the miniaturization and hierarchical organization of the central nervous system. Biosci Rep 4:93–98PubMedCrossRefGoogle Scholar
  4. Agnati LF, Fuxe K, Ferri M, Benfenati F, Ogren SO (1981) A new hypothesis on memory. A possible role of local circuits in the formation of memory trace. Med Biol 59:224–229PubMedGoogle Scholar
  5. Agnati LF, Fuxe K, Zoli M, Rondanini C, Ogren SO (1982) New vistas on synaptic plasticity: the receptor mosaic hypothesis of the engram. Med Biol 60:183–190PubMedGoogle Scholar
  6. Agnati LF, Santarossa L, Benfenati F (2002) Molecular basis of learning and memory: modeling based on receptor mosaics. In: Apolloni B, Kurfes F et al (eds) From synapses to rules. Kluwer Academic/Plenum Publishers, New York, pp 165–196Google Scholar
  7. Agnati LF, Franzen O, Ferré S, Leo G, Franco R, Fuxe K (2003) Possible role of intramembrane receptor–receptor interactions in memory and learning via formation of long-lived heteromeric complexes: focus on motor learning in the basal ganglia. J Neural Transm 65:195–222Google Scholar
  8. Agnati LF, Santarossa L, Genedani S (2004) On the nested hierarchical organization of CNS: basic characteristics of neuronal molecular networks. In: Erdi P, Esposito A, Marinaro M, Scarpetta S et al (eds) Computational neuroscience: cortical dynamics, lecture notes in computer sciences. Springer, Berlin, pp 24–54Google Scholar
  9. Agnati LF, Guidolin D, Genedani S et al (2005a) How proteins come together in the plasma membrane and function in macromolecular assemblies: focus on receptor mosaics. J Mol Neurosci 26:133–154PubMedCrossRefGoogle Scholar
  10. Agnati LF, Tarakanov AO, Guidolin D (2005b) A simple mathematical model of cooperativity in receptor mosaics based on the “symmetry rule”. Biosystems 80:165–173PubMedCrossRefGoogle Scholar
  11. Agnati LF, Leo G, Zanardi A et al (2006a) Volume transmission and wiring transmission from cellular to molecular networks: history and perspectives. Acta Physiol 187:329–344CrossRefGoogle Scholar
  12. Agnati LF, Zunarelli E, Genedani S, Fuxe K (2006b) On the existence of a global molecular network enmeshing the whole central nervous system: physiological and pathological implications. Curr Protein Pept Sci 7:3–15PubMedCrossRefGoogle Scholar
  13. Agnati LF, Genedani S, Leo G, Rivera A, Guidolin D, Fuxe K (2007a) One century of progress in neuroscience founded on Golgi and Cajal’s outstanding experimental and theoretical contributions. Brain Res Rev 55:167–189PubMedCrossRefGoogle Scholar
  14. Agnati LF, Agnati A, Mora F, Fuxe K (2007b) Does the human brain have unique genetically determined networks coding logical and ethical principles and aesthetics? From Plato to novel mirror networks. Brain Res Rev 55:68–77PubMedCrossRefGoogle Scholar
  15. Agnati A, Guidolin D, Carone C, Dam M, Genedani S, Fuxe K (2008) Understanding neuronal molecular network architecture builds on neuronal cellular network architecture. Brain Res Rev 58:379–399PubMedCrossRefGoogle Scholar
  16. Allen JA, Halverson-Tamboli RA, Rasenick MM (2007) Lipid raft microdomains and neurotransmitter signalling. Nat Rev Neurosci 8:128–140PubMedCrossRefGoogle Scholar
  17. Baluška F, Volkmann D, Barlow PW (2001) Motile plant cell body: a ‘bug’ within a ‘cage’. Trends Plant Sci 6:104–111PubMedCrossRefGoogle Scholar
  18. Baluška F, Volkmann D, Barlow PW (2004a) Cell bodies in a cage. Nature 428:371PubMedCrossRefGoogle Scholar
  19. Baluška F, Volkmann D, Barlow PW (2004b) Eukaryotic cells and their cell bodies: cell theory revisited. Ann Bot 94:9–32PubMedCrossRefGoogle Scholar
  20. Baluška F, Hlavacka A, Volkmann D, Barlow PW (2004c) Getting connected: actin-based cell-to-cell channel in plants and animal. Trends Cell Biol 14:404–408PubMedCrossRefGoogle Scholar
  21. Baluška F, Volkmann D, Barlow PW (2006a) Cell–cell channels and their implications for cell theory. In: Baluška F, Volkmann D, Barlow DW (eds) Cell–cell channels. Landes Bioscience, Georgetown, pp 1–18CrossRefGoogle Scholar
  22. Baluška F, Menzel D, Barlow PW (2006b) Cytokinesis in plant and animal cells: endosomes ‘shut the door’. Dev Biol 294:1–10PubMedCrossRefGoogle Scholar
  23. Cajal SR (1894) Les nouvelles idées sur la structure du systéme nerveux. Chez l’ homme et chez les vertébrés, Reinwald, ParisGoogle Scholar
  24. Cajal SR (1906) The structure and connexions of neurons. Nobel lecture. Elsevier, AmsterdamGoogle Scholar
  25. Croll D, Giovannetti M, Koch AM, Sbrana C, Ehinger M, Lammers PJ, Sanders IR (2008) Nonself vegetable fusion and genetic exchange in the arbuscular mycorrhizal fungus Glomus intraradices. New Phytol 181:924–937CrossRefGoogle Scholar
  26. Demontis F (2004) Nanotubes make big science. PloS Biol 2:E215PubMedCrossRefGoogle Scholar
  27. Dhonukshe P, Mathur J, Hülskamp M, Gadella TW Jr (2005) Microtubule plus-ends reveal essential links between intracellular polarization and localized modulation of endocytosis during division-plane establishment in plant cells. BMC Biol 3:11PubMedCrossRefGoogle Scholar
  28. Dhonukshe P, Baluska F, Schlicht M, Hlavacka A, Samaj J, Friml J, Gadella TW Jr (2006) Endocytosis of cell surface material mediates cell plate formation during plant cytokinesis. Dev Cell 10:137–150PubMedCrossRefGoogle Scholar
  29. Eyman M, Cefaliello C, Ferrara E et al (2007) Local synthesis of axonal and presynaptic RNA in squid model systems. Eur J Neurosci 25:341–350PubMedCrossRefGoogle Scholar
  30. Faeder JR, Blinov ML, Goldstein B, Hlavacek WS (2005) Rule-based modeling of biochemical networks. Complexity 10:22–41CrossRefGoogle Scholar
  31. Gerdes HH, Bukoreshtliev NV, Barroso JF (2007) Tunneling nanotubes: a new route for the exchange of components between animal cells. FEBS Lett 581:2194–2201PubMedCrossRefGoogle Scholar
  32. Giovannetti M, Fortuna P, Citernesi AS, Morini S, Nuti MP (2001) The occurrence of anastomosis formation and nuclear exchange in intact arbuscular mycorrhizal networks. New Phytol 151:717–724CrossRefGoogle Scholar
  33. Giovannetti M, Avio L, Fortuna P, Pellegrino E, Sbrana C, Strani C (2006) At the root of the wood wide web. Self recognition and non-self incompatibility in mycorrhizal networks. Plant Signal Behav 1:1–5PubMedGoogle Scholar
  34. Giuditta A, Chun JT, Eyman M, Cefaliello C, Bruno AP, Crispino M (2008) Local gene expression in axons and nerve endings: the glia–neuron unit. Physiol Rev 88:515–555PubMedCrossRefGoogle Scholar
  35. Goldman-Rakic P (1975) Local circuit neurons. Neurosci Res Program Bull 13:299–313Google Scholar
  36. Griffiths JB (1972) The effect of cell population density on nutrient uptake and cell metabolism: a comparative study of human diploid and heteroploid cell lines. J Cell Sci 10:515–524PubMedGoogle Scholar
  37. Guidolin D, Fuxe K, Neri G, Nussdorfer GG, Agnati LF (2007) On the role of receptor–receptor interactions and volume transmission in learning and memory. Brain Res Rev 55:119–133PubMedCrossRefGoogle Scholar
  38. Guillery RW (2005) Observations of synaptic structures: origins of the neuron doctrine and its current status. Philos Trans R Soc Lond B Biol Sci 360:1281–1307PubMedCrossRefGoogle Scholar
  39. Hijri M, Sanders IR (2005) Low gene copy number shows that arbuscular mycorrhiza fungi inherit genetically different nuclei. Nature 433:160–163PubMedCrossRefGoogle Scholar
  40. Jacobson M (1993) Foundations of neuroscience. Plenum Press, New YorkGoogle Scholar
  41. Johansson CB, Youssef S, Koleckar K et al (2008) Extensive fusion of haematopoietic cells with Purkinje neurons in response to chronic inflammation. Nat Cell Biol 10:575–583PubMedCrossRefGoogle Scholar
  42. Johnson LR, Byrne JH (eds) (1998) Essential medical physiology. Lippincott–Raven, PhiladelphiaGoogle Scholar
  43. Kauffman SA (1993) The origin of order. Oxford University Press, New YorkGoogle Scholar
  44. Kholodenko BN (2006) Cell-signalling dynamics in time and space. Nat Rev Mol Cell Biol 7:165–176PubMedCrossRefGoogle Scholar
  45. Kim GH, Klotchkova TA, Kang YM (2001) Life without a cell membrane: regeneration of protoplasts from disintegrated cells of the marine green alga Bryopsis plumosa. J Cell Sci 114:2009–2014PubMedGoogle Scholar
  46. Kleene R, Schachner M (2004) Glycans and neural cell interactions. Nat Rev Neurosci 5:195–208PubMedCrossRefGoogle Scholar
  47. Kolch W (2005) Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat Rev Mol Cell Biol 6:827–837PubMedCrossRefGoogle Scholar
  48. Kuhn T (1996) The structure of scientific revolutions. The University of Chicago Press, ChicagoGoogle Scholar
  49. Kuhn G, Hijri M, Sanders IR (2001) Evidence for the evolution of multiple genomes in arbuscular mycorrhizal fungi. Nature 414:745–748PubMedCrossRefGoogle Scholar
  50. Lauffenburger DA (2000) Cell signaling pathways as control modules: complexity for simplicity? Proc Natl Acad Sci USA 97:5031–5033PubMedCrossRefGoogle Scholar
  51. Marr D (1969) A theory of cerebellar cortex. J Physiol 202:437–470PubMedGoogle Scholar
  52. McCulloch WS, Pitts WH (1943) A logical calculus of the ideas immanent in nervous activity. Bull Math Biophys 5:11–133CrossRefGoogle Scholar
  53. Mix MC, Farber P, King KI (1996) Biology: the network of life. HarperCollins, New YorkGoogle Scholar
  54. Nakamura T, Asakawa H, Nakase Y, Kashiwazaki J, Hiraoka Y, Shimoda C (2008) Live observation of forespore membrane formation in fission yeast. Mol Biol Cell 19:3544–3553PubMedCrossRefGoogle Scholar
  55. Neiman AJ (2005) Ascospore formation in the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev 69:564–565CrossRefGoogle Scholar
  56. Nygren JM, Liuba K, Breitbach M et al (2008) Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion. Nat Cell Biol 10:584–592PubMedCrossRefGoogle Scholar
  57. Okamoto T, Schlegel A, Scherer PE, Lisanti MP (1998) Caveolins, a family of scaffolding proteins for organizing “preassembled signaling complexes” at the plasma membrane. J Biol Chem 273:5419–5422PubMedCrossRefGoogle Scholar
  58. Onfelt B, Davis DM (2004) Can membrane nanotubes facilitate communication between immune cells? Biochem Soc Trans 32:676–678PubMedCrossRefGoogle Scholar
  59. Ovádi J, Saks V (2004) On the origin of intracellular compartmentation and organized metabolic systems. Mol Cell Biochem 256–257:5–12PubMedCrossRefGoogle Scholar
  60. Ram M, Babbar SM (2002) Transient existence of life without a cell membrane: a novel strategy of siphonous seaweed for survival and propagation. Bioessays 24:588–590PubMedCrossRefGoogle Scholar
  61. Rhoades RA, Tanner A (1995) Medical physiology. Little Brown, New YorkGoogle Scholar
  62. Rustom A, Saffrich R, Markovic I, Walther P, Gerdes HH (2004) Nanotubular highways for intercellular organelle transport. Science 303:1007–1010PubMedCrossRefGoogle Scholar
  63. Sachs J (1892) Beiträge zur Zellentheorie. Energiden und Zellen. Flora 75:57–67Google Scholar
  64. Sanders IR (2002) Ecology and evolution of multigenomic arbuscular mycorrhizal fungi. Am Nat 160:S128–S141PubMedCrossRefGoogle Scholar
  65. Sauro HM, Kholodenko BN (2004) Quantitative analysis of signaling networks. Prog Biophys Mol Biol 86:5–43PubMedCrossRefGoogle Scholar
  66. Segev I, Rall W (1998) Excitable dendrites and spines: earlier theoretical insights elucidate recent direct observations. Trends Neurosci 21:453–460PubMedCrossRefGoogle Scholar
  67. Schrödinger E (1944) What is life? The physical aspects of the living cell. Cambridge University Press, CambridgeGoogle Scholar
  68. Shepherd GM (1991) Foundations of neuron doctrine. Oxford University Press, New YorkGoogle Scholar
  69. Shepherd VA, Beilby MJ, Bisson MA (2004) When is a cell not a cell? A theory relating coenocytic structure to the unusual electrophysiology of Ventricaria ventricosa (Valonia ventricosa). Protoplasma 223:79–91PubMedCrossRefGoogle Scholar
  70. Shimoda C (2004) Forespore membrane assembly in yeast: coordinating SPBs and membrane trafficking. J Cell Sci 117:389–396PubMedCrossRefGoogle Scholar
  71. Singec I, Snyder EY (2008) Inflammation as a matchmaker: revisiting cell fusion. Nat Cell Biol 10:503–505PubMedCrossRefGoogle Scholar
  72. Toussaint O, Schneider ED (1998) The thermodynamics and evolution of complexity in biological systems. Comp Biochem Physiol A Mol Integr Physiol 120:3–9PubMedCrossRefGoogle Scholar
  73. Verkman AS (2002) Solute and macromolecule diffusion in cellular aqueous compartment. Trends Biochem Sci 27:27–33PubMedCrossRefGoogle Scholar
  74. Wuensche A (2003) Discrete Dynamics Lab: tools for investigating cellular automata and discrete dynamical networks. Kybernetes 32:77–99CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • L. F. Agnati
    • 1
    • 2
  • K. Fuxe
    • 3
  • F. Baluška
    • 4
  • D. Guidolin
    • 5
  1. 1.Section of Physiology, Department of Biomedical SciencesUniversity of Modena and Reggio EmiliaModenaItaly
  2. 2.IRCCS, Ospedale San CamilloVenetiaItaly
  3. 3.Department of NeuroscienceKarolinska InstitutetStockholmSweden
  4. 4.Department of Plant Cell BiologyUniversity of BonnBonnGermany
  5. 5.Department of Human Anatomy and PhysiologyUniversity of PadovaPaduaItaly

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