Journal of Neural Transmission

, Volume 125, Issue 6, pp 883–897 | Cite as

The brain as a “hyper-network”: the key role of neural networks as main producers of the integrated brain actions especially via the “broadcasted” neuroconnectomics

  • Luigi F. Agnati
  • Manuela Marcoli
  • Guido Maura
  • Amina Woods
  • Diego Guidolin
Translational Neurosciences - Review Article


Investigations of brain complex integrative actions should consider beside neural networks, glial, extracellular molecular, and fluid channels networks. The present paper proposes that all these networks are assembled into the brain hyper-network that has as fundamental components, the tetra-partite synapses, formed by neural, glial, and extracellular molecular networks. Furthermore, peri-synaptic astrocytic processes by modulating the perviousness of extracellular fluid channels control the signals impinging on the tetra-partite synapses. It has also been surmised that global signalling via astrocytes networks and highly pervasive signals, such as electromagnetic fields (EMFs), allow the appropriate integration of the various networks especially at crucial nodes level, the tetra-partite synapses. As a matter of fact, it has been shown that astrocytes can form gap-junction-coupled syncytia allowing intercellular communication characterised by a rapid and possibly long-distance transfer of signals. As far as the EMFs are concerned, the concept of broadcasted neuroconnectomics (BNC) has been introduced to describe highly pervasive signals involved in resetting the information handling of brain networks at various miniaturisation levels. In other words, BNC creates, thanks to the EMFs, generated especially by neurons, different assemblages among the various networks forming the brain hyper-network. Thus, it is surmised that neuronal networks are the “core components” of the brain hyper-network that has as special “nodes” the multi-facet tetra-partite synapses. Furthermore, it is suggested that investigations on the functional plasticity of multi-partite synapses in response to BNC can be the background for a new understanding and perhaps a new modelling of brain morpho-functional organisation and integrative actions.


Network science Brain circuits’ miniaturisation levels Tetra-partite synapses Electromagnetic fields Broadcasted neuroconnectomics Global integrative actions 



Action potentials


Brain hyper-network


Broadcasted neuroconnectomics


Central nervous system


Cerebro-spinal fluid


Chondroitin sulfate proteoglycans


Extracellular matrix


Extracellular space




Extracellular fluid channels networks


Electromagnetic fields


Extracellular molecular networks


Functional modules


Glia networks


Horizontal networks


Local field potentials


Modular network model


Neural networks




Peri-synaptic astrocytic processes


Perineuronal nets




Receptor mosaic


Voltage-gated calcium channels


Volume transmission


Wiring transmission



Funding this work was supported by the University of Genova [Grant 020301002054 to M.M.]; and the University of Padova [Grant 60A06-0481/14 to D.G.].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Diagnostic, Clinical Medicine and Public HealthUniversity of Modena and Reggio EmiliaModenaItaly
  2. 2.Department of NeuroscienceKarolinska InstitutetStockholmSweden
  3. 3.Section of Pharmacology and Toxicology, Department of PharmacyUniversity of GenovaGenoaItaly
  4. 4.Centre of Excellence for Biomedical Research CEBR, University of GenovaGenoaItaly
  5. 5.Structural Biology UnitNational Institutes of Health, National Institute of Drug Abuse-Intramural Research ProgramBaltimoreUSA
  6. 6.Department of Molecular MedicineUniversity of PadovaPaduaItaly

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