Systems neuroscienceA role for glutamate and glia in the fast network oscillations preceding spreading depression
Section snippets
In vitro experiments
The experiments followed European Community regulations on animal care and handling and were approved by the Research Committee of the Ramón y Cajal Hospital of Madrid. Every effort was made to minimize the number of animals used and their suffering.
Hippocampal slices were prepared from female Sprague–Dawley rats (80–150 g) using standard techniques. Briefly, the animal was anesthetized with ether, decapitated and the brain removed to chilled artificial cerebrospinal fluid (ACSF). Parasagittal
Spatial features of field oscillations and the burst of PSs preceding SD in vitro
In control slices, SD waves elicited in the subicular side of the CA1 field traveled to the fimbrial side reaching the CA3 border, where they stopped. In the front of an SD wave approaching the electrode, several seconds before the onset of the characteristic sustained negative Vo, fast electrical activity was detected which subsided with the initiation of the negative DC swing (Fig. 1A). It consisted initially of a low-amplitude (0.1–0.15 mV) rhythmic (80–115 Hz) sine-like signal, which gave
Discussion
The present study focused on the mechanisms of the oscillatory field activity and firing synchronization that occurs before the inactivating depolarization associated with SD. The results suggest that endogenous Glu acting on ionotropic Glu receptors up-regulates the oscillation frequency and firing synchronization, and speeds SD migration. The metabolic poisoning of glia first increased the frequency of oscillations by a glutamatergic action, and then caused disorganization. Prolonged
Conclusion
Multiple cellular and subcellular mechanisms are activated for the propagation and depolarizing phases of SD. The present results are compatible with a glutamatergic action mediated by glia and/or neuron–glia interactions in the leading front of SD waves, and open the possibility of a participation of glia in the hypersynchronization of neuron firing by modulating synchronous oscillations between nearby neurons, which may be relevant for the treatment of stroke and epilepsy.
Acknowledgments
We thank Prof. G. G. Somjen for the critical reading of the manuscript, M. J. Yagüe for technical assistance, and American Journal Experts DLL for help with English edition. This work has been supported by grants 8.5/15/98 of the Comunidad Autónoma de Madrid and PB97/1448, BEFI 2002/1767, and BFU2005/8917 of the Spanish Ministries of Education, Science and Technology.
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Cortical Spreading Depression and Ischemia in Neurocritical Patients
2018, Neurosurgery Clinics of North AmericaCortical Spreading Depression and Ischemia in Neurocritical Patients
2017, Neurologic ClinicsCitation Excerpt :In hypoxic, ischemic, glycopenic brain tissue, CSD will usually occur spontaneously, and recovery is slow.4 The SD of neurons and glia is preceded by propagating field oscillations covering distances of up to 1 mm.5 These oscillations indicate a brief state of hyperexcitability, which may relate to the observation of seizures and CSD in the same patients with acutely injured brain cortex.6
Effects of experimental traumatic brain injury and impaired glutamate transport on cortical spreading depression
2017, Experimental NeurologyCitation Excerpt :CSD can be observed in damaged brain regions and during the course of epileptic seizures (Lauritzen et al., 2011), but it can also be induced experimentally by raising glutamate or K+, manipulating Na+/K+ pump inhibitors, by using electrical stimulation or hyperthermia (Malkov et al., 2014). Electrically, CSD is characterized by profound depolarization of neuronal networks, followed by slow propagation (2–5 mm/min) of this depolarizing wave (Lauritzen et al., 2011; Larrosa et al., 2006). During the initial depolarizing portion of CSD, the extracellular glutamate and aspartate concentrations increase (Van Harreveld and Fifkova, 1970; Fabricius et al., 1993).
Importance of astrocytes for potassium ion (K<sup>+</sup>) homeostasis in brain and glial effects of K<sup>+</sup> and its transporters on learning
2016, Neuroscience and Biobehavioral ReviewsCitation Excerpt :However, it should also be remembered that the propagation of spreading depression in vivo is synchronous with neuronal oscillations in a strip of tissue ahead of the depolarizing wave, which begins before the rise of [K+]o and is followed by a minute-long loss of neuronal activity before complete recovery (Herreras et al., 1994; Lauritzen et al., 2011). Blockade of ionotropic glutamate receptors decreases the frequency of prodromal oscillations, retards spreading depression and shortens the duration of depolarization, whereas inhibition of glutamate uptake increases the oscillatory frequency (Larrosa et al., 2006). Selective metabolic poisoning of astrocytes first increases and later decreases oscillatory frequency and amplitude at a time when neuronal electrical properties are still normal (Larrosa et al., 2006), and it lowers a largely increased release of glutamate (Szerb, 1991).
The Comorbidity of Migraine and Epilepsy in Children and Adolescents
2016, Seminars in Pediatric NeurologyCitation Excerpt :The link to the CSD concept in epilepsy was demonstrated by Herreras et al42, who demonstrated that neuronal synchronization and field oscillations precede the onset of CSD and changes in neuronal excitability.42 This synchronization has been hypothesized to be caused by nonsynaptic interactions between neurons, possibly mediated through the excitatory neurotransmitter glutamate, which when release from glial cells has been shown to trigger CSD.43 In addition, glutamate antagonists that act as N-methyl-D-aspartate receptor channel blockers result in diminished organization and inhibition of the fast oscillations preceding CSD.43
- 1
Present address: Department of Clinical Neurophysiology, Epilepsy Unit, Hospital de la Princesa, Madrid 28006, Spain (J. Pastor); Department of Applied Mathematics, School of Optics, University Complutense of Madrid, Madrid 28040, Spain (L. López-Aguado).
- 2
These authors contributed equally to this work.