Elsevier

Neuroscience

Volume 370, 1 February 2018, Pages 37-45
Neuroscience

Review
Ephaptic Coupling of Cortical Neurons: Possible Contribution of Astroglial Magnetic Fields?

https://doi.org/10.1016/j.neuroscience.2017.07.072Get rights and content

Highlights

  • To review the current knowledge supporting the contribution of neurons and astrocytes on ephaptic neuronal modulation.

  • To suggest that astroglial magnetic fields associated with Ca2+ waves may play a role in the ephaptic coupling of neurons.

  • To propose that the ultrastructural organization of the mammalian neocortex is appropriated for bio-magnetic interactions.

Abstract

The close anatomical and functional relationship between neuronal circuits and the astroglial network in the neocortex has been demonstrated at several organization levels supporting the idea that neuron-astroglial crosstalk can play a key role in information processing. In addition to chemical and electrical neurotransmission, other non-synaptic mechanisms called ephaptic interactions seem to be important to understand neuronal coupling and cognitive functions. Recent interest in this issue comes from the fact that extra-cranial electric and magnetic field stimulations have shown therapeutic actions in the clinical practice. The present paper reviews the current knowledge regarding the ephaptic effects in mammalian neocortex and proposes that astroglial bio-magnetic fields associated with Ca2+ transients could be implicated in the ephaptic coupling of neurons by a direct magnetic modulation of the intercellular local field potentials.

Introduction

In addition to chemical and electrical neurotransmission, other non-synaptic mechanisms such as extracellular ionic waves and changes in osmolarity have been considered critical for coupling and synchronization of neurons into the neocortex both, in physiological and pathological conditions (Rosen and Andrew, 1990, Syková, 2004, Durand et al., 2010). These other ways of neuronal modulation are known as ephaptic interaction (Katz and Schmitt, 1940, Arvanitaki, 1942), and, recently it has been recognized that this type of communication may play a central role in cognitive functions (Buzsáki et al., 2012, Reimann et al., 2013). On the other hand, ephaptic effects may help to explain, at least partially, the therapeutic actions of transcranial electric and magnetic field stimulation (Peterchev et al., 2012). The ephaptic effect in the neocortex is thought to be due to the summation of all sources that contribute to the extracellular field potential. This extracellular potential in a point of the neocortex results from the addition of synaptic currents, action potential currents as well as astroglial ionic currents around this point (Jefferys and Haas, 1982, Jefferys, 1995, Ray, 2015), and it is called the local field potential (LFP). Classically, the effects of the action potentials and astroglial ionic currents have been considered negligible in comparison to the contribution of synaptic currents (Creutzfeldt and Houchin, 1974, Mitzdorf, 1985). Therefore, the contribution of astroglial bio-electric and bio-magnetic fields to the LFPs into the neocortex has been scarcely studied. In the present paper, I conjecture that bio-electro-magnetic fields generated inside the astroglial syncytium around neurons may contribute to the so-called ephaptic effects in the neocortex, playing a role in the modulation and synchronization of neuronal behavior.

Section snippets

Architectural considerations of the mammalian neocortex

The recognition of the huge number and wide diversity of cell types, complex 3D organization, functional architecture and connectivity in the mammalian cerebral cortex, begun with the Cajal’s studies (Ramón y Cajal, 1897) and continue today with the Blue Brain Project (Markram et al., 2015). From a schematic point of view, the mammalian neocortex is composed of neuronal and glial cells organized fundamentally in two closely related 3D structures (Fig. 1). The neurocortex is organized in

Neuron-astroglial interplay: electrophysiological and ionic considerations

The close anatomical and functional relationship between neuronal circuits and the astroglial network in the neocortex has been demonstrated at several organization levels. For instance, many experiments have shown an exquisite electrophysiological interplay between neurons and astrocytes in the mammalian neocortex supporting the notion that neuron-astroglial crosstalk could play a central role in information processing (Amzica and Steriade, 2000, Araque et al., 2001, Araque et al., 2014,

Bio-electro-magnetic fields in the neocortex

Correlation between electroencephalography (EEG) and magnetoencephalography (MEG) is very high (Cuffin and Cohen, 1979), but MEG records rhythmic and coherent magnetic fields generated mainly in cortical pyramidal cells (Gallen et al., 1995). The recorded fields are the result of the coordinated firing of many thousands of these cells, mostly located in layers III and IV of the neocortex (Nunez, 1986, Hamalainen et al., 1993). The magnetic fields, recorded above the surface of the scalp, are in

Ephaptic neuronal coupling: astroglial magnetic field effects?

It is a fact, that neuronal behavior is affected by adjacent neuronal activities in the cerebral cortex via ephaptic interaction. Experiments in goldfish showed an ephaptic inhibitory action on the Mauthner cells (Furukawa and Furshpan, 1963), and electrical interactions have been demonstrated to excite many interneurons playing important roles in neuronal circuits (Faber and Korn, 1983, Hu et al., 2000, Weiss et al., 2008). In addition, it has been suggested that cells could communicate by

Ephaptic effects in transcranial field stimulation

Transcranial electric and magnetic field stimulation of the brain have shown a wide variety of therapeutic and cognitive effects, using different techniques, stimulus waveforms, and designs (Weiss and Faber, 2010, Peterchev et al., 2012). In the case of transcranial magnetic stimulation, a magnetic field is generated that induces an electric field and its corresponding current density field in the brain (Peterchev et al., 2012). However, the specific mechanisms that mediate their clinical and

Conclusion

In recent years, an increasing role of astrocytes in the mammalian neocortical structure and function has been demonstrated. In addition to the structural, metabolic and ionic homeostatic support to neurons, astroglia plays a central role in neuromodulation and computation, including fundamental roles in superior cognitive function in the mammalian neocortex. The contribution of the astroglial network to the synaptic communication and remodeling is now well recognized, but a widespread role of

References (121)

  • E.A. Newman

    New roles for astrocytes: regulation of synaptic transmission

    Trends Neurosci

    (2003)
  • U. Pannasch et al.

    Emerging role for astroglial networks in information processing: from synapse to behavior

    Trends Neurosci

    (2013)
  • A.V. Peterchev et al.

    Fundamentals of transcranial electric and magnetic stimulation dose: definition, selection, and reporting practices

    Brain Stimulation

    (2012)
  • S. Ray

    Challenges in the quantification and interpretation of spike-LFP relationships

    Curr Opin Neurobiol

    (2015)
  • M.W. Reimann et al.

    A biophysically detailed model of neocortical local field potentials predicts the critical role of active membrane currents

    Neuron

    (2013)
  • A.S. Rosen et al.

    Osmotic effects upon excitability in rat neocortical slices

    Neuroscience

    (1990)
  • W.R. Adey
  • F. Aguado et al.

    Neuronal activity regulates correlated network properties of spontaneous calcium transients in astrocytes in situ

    J Neurosci

    (2002)
  • C. Agulhon et al.

    Hippocampal short- and long-term plasticity are not modulated by astrocyte Ca2+ signaling

    Science

    (2010)
  • Z. Ahmed et al.

    Modulation of learning and hippocampal neuronal plasticity by repetitive transcranial magnetic stimulation (rTMS)

    Bioelectromagnetics

    (2006)
  • F. Amzica et al.

    Glial and neuronal interactions during slow wave and paroxysmal activities in the neocortex

    Cereb Cortex

    (2002)
  • F. Amzica et al.

    Neuronal and glial membrane potentials during sleep and paroxismal oscillations in the neocortex

    J Neurosci

    (2000)
  • C.A. Anastassiou et al.

    The effect of spatially inhomogeneous extracellular electric fields on neurons

    J Neurosci

    (2010)
  • C.A. Anastassiou et al.

    Ephaptic coupling of cortical neurons

    Nature Neurosci

    (2011)
  • M.C. Angulo et al.

    Glutamate released from glial cells synchronizes neuronal activity in the hippocampus

    J Neurosci

    (2004)
  • A. Araque et al.

    Dynamic signalling between astrocytes and neurons

    Ann Rev Physiol

    (2001)
  • G. Ardolino et al.

    Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain

    J Physiol

    (2005)
  • A. Arvanitaki

    Effects evoked in an axon by the activity of a contiguous one

    J Neurophysiol

    (1942)
  • M. Bikson et al.

    Suppression of epileptiform activity by high frequency sinusoidal fields in rat hippocampal slices

    J Physiol

    (2001)
  • J.R. Bradley et al.

    The magnetic field of a single axon: a comparison of theory and experiment

    Biophys J

    (1985)
  • T.H. Bullock

    Signals and signs in the nervous system: the dynamic anatomy of electrical activity is probably information-rich

    Proc Natl Acad Sci USA

    (1997)
  • D.P. Buxhoeveden et al.

    The minicolumn hypothesis in neuroscience

    Brain

    (2002)
  • G. Buzsáki et al.

    The origin of extracellular fields and currents — EEG, ECoG, LFP and spikes

    Nat Rev Neurosci

    (2012)
  • A.V. Cavopol et al.

    Measurement and analysis of static magnetic fields that block action potentials in cultured neurons

    Bioelectromagnetics

    (1995)
  • J.H. Chien et al.

    Understanding transcranial magnetic stimulation: a new study of high-temporal-resolution cortical single-neuron responses with extensive artifact reduction

    Neurosurgery

    (2014)
  • A. Chvatal et al.

    Glial depolarization evokes a larger potassium accumulation around oligodendrocytes than around astrocytes in gray matter of rat spinal cord slices

    J Neurosci Res

    (1999)
  • B.G. Cragg

    Ultrastructural features of human cerebral cortex

    J Anat

    (1976)
  • O.D. Creutzfeldt et al.

    Neuronal basis of EEG waves

  • B.N. Cuffin et al.

    Comparison of the magnetoencephalogram and electroencephalogram

    Electroencephalogr Clin Neurophysiol

    (1979)
  • C.L. Cullen et al.

    How does transcranial magnetic stimulation influence glial cells in the central nervous system?

    Front Neural Circuits

    (2016)
  • J.K. Deans et al.

    Sensitivity of coherent oscillations in rat hippocampus to AC electric fields

    J Physiol

    (2007)
  • J. DeFelipe et al.

    Microstructure of the neocortex: comparative aspects

    J Neurocytol

    (2002)
  • F. Ding et al.

    Α1-adrenergic receptors mediate coordinated Ca2+ signaling of cortical astrocytes in awake, behaving mice

    Cell Calcium

    (2013)
  • D.M. Durand et al.

    Potassium diffusive coupling in neural networks

    Philos Trans R Soc Lond B Biol Sci

    (2010)
  • R. Eilam et al.

    Astrocyte morphology is confined by cortical functional boundaries in mammals ranging from mice to human

    eLife

    (2016)
  • D.S. Faber et al.

    Field effects trigger post-anodal rebound excitation in vertebrate CNS

    Nature

    (1983)
  • J.T. Francis et al.

    Sensitivity of neurons to weak electric fields

    J Neurosci

    (2003)
  • T. Furukawa et al.

    Two inhibitory mechanisms in the Mauthner neurons of goldfish

    J Neurophysiol

    (1963)
  • C.C. Gallen et al.

    Magnetoencephalography and magnetic source imaging: Capabilities and limitations

    Neuroimaging Clin N Am

    (1995)
  • Georgiev D (2003) Electric and magnetic fields inside neurons and their impact upon the cytoskeletal microtubules....
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