Neuron to astrocyte communication via cannabinoid receptors is necessary for sustained epileptiform activity in rat hippocampus

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Coiret, Guyllaume ; Ster, Jeanne ; Grewe, Benjamin ; Wendling, Fabrice ; Helmchen, Fritjof ; Gerber, Urs ; Benquet, Pascal (2012)
  • Publisher: Public Library of Science (PLoS)
  • Journal: volume 7, issue 5 (issn: 1932-6203, eissn: 1932-6203)
  • Related identifiers: pmc: PMC3352897, doi: 10.5167/uzh-74280, doi: 10.1371/journal.pone.0037320
  • Subject: epilepsy | Research Article | Cell Physiology | patch-clamp | 610 Medicine & health | Neural Networks | neuron | slice | Neurotransmitters | Neurological System | astrocyte | Neurology | Neurobiology of Disease and Regeneration | Temporal Lobe Epilepsy | two-photon | Biology | hippocampus | Neuroscience | Brain Research Institute | Medicine | Ion Channels | Anatomy and Physiology | Cellular Neuroscience | Q | R | CB1 | Synapses | electrophysiology | [ SCCO.NEUR ] Cognitive science/Neuroscience | Science | 570 Life sciences; biology | Neurophysiology | calcium imaging
    mesheuropmc: musculoskeletal, neural, and ocular physiology | nervous system

International audience; Astrocytes are integral functional components of synapses, regulating transmission and plasticity. They have also been implicated in the pathogenesis of epilepsy, although their precise roles have not been comprehensively characterized. Astrocytes integrate activity from neighboring synapses by responding to neuronally released neurotransmitters such as glutamate and ATP. Strong activation of astrocytes mediated by these neurotransmitters can promote seizure-like activity by initiating a positive feedback loop that induces excessive neuronal discharge. Recent work has demonstrated that astrocytes express cannabinoid 1 (CB1) receptors, which are sensitive to endocannabinoids released by nearby pyramidal cells. In this study, we tested whether this mechanism also contributes to epileptiform activity. In a model of 4-aminopyridine induced epileptic-like activity in hippocampal slice cultures, we show that pharmacological blockade of astrocyte CB1 receptors did not modify the initiation, but significantly reduced the maintenance of epileptiform discharge. When communication in astrocytic networks was disrupted by chelating astrocytic calcium, this CB1 receptor-mediated modulation of epileptiform activity was no longer observed. Thus, endocannabinoid signaling from neurons to astrocytes represents an additional significant factor in the maintenance of epileptiform activity in the hippocampus.
  • References (46)
    46 references, page 1 of 5

    1. Vesce S, Bezzi P, Volterra A (1999) The active role of astrocytes in synaptic transmission. Cell Mol Life Sci 56: 991-1000.

    2. Araque A, Parpura V, Sanzgiri RP, Haydon PG (1999) Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci 22: 208-215.

    3. Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32: 421-431.

    4. Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6: 626-640.

    5. Halassa MM, Haydon PG (2010) Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior. Annu Rev Physiol 72: 335-355.

    6. Hamilton NB, Attwell D (2010) Do astrocytes really exocytose neurotransmitters? Nat Rev Neurosci 11: 227-238.

    7. Angulo MC, Kozlov AS, Charpak S, Audinat E (2004) Glutamate released from glial cells synchronizes neuronal activity in the hippocampus. J Neurosci 24: 6920-6927.

    8. Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, et al. (2004) Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43: 729-743.

    9. Gomez-Gonzalo M, Losi G, Brondi M, Uva L, Sato SS, et al. (2011) Ictal but not interictal epileptic discharges activate astrocyte endfeet and elicit cerebral arteriole responses. Front Cell Neurosci 5: 8.

    10. Gomez-Gonzalo M, Losi G, Chiavegato A, Zonta M, Cammarota M, et al. (2010) An excitatory loop with astrocytes contributes to drive neurons to seizure threshold. PLoS Biol 8: e1000352.

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