Journal article
Traumatic Alterations in GABA Signaling Disrupt Hippocampal Network Activity in the Developing Brain
The Journal of neuroscience, Vol.32(12), pp.4017-4031
03/21/2012
DOI: 10.1523/JNEUROSCI.5139-11.2012
PMCID: PMC3333790
PMID: 22442068
Abstract
Severe head trauma causes widespread neuronal shear injuries and acute seizures. Shearing of neural processes might contribute to seizures by disrupting the transmembrane ion gradients that subserve normal synaptic signaling. To test this possibility, we investigated changes in intracellular chloride concentration ([Cl
−
]
i
) associated with the widespread neural shear injury induced during preparation of acute brain slices. In hippocampal slices and intact hippocampal preparations from immature CLM-1 mice, increases in [Cl
−
]
i
correlated with disruption of neural processes and biomarkers of cell injury. Traumatized neurons with higher [Cl
−
]
i
demonstrated excitatory GABA signaling, remained synaptically active, and facilitated network activity as assayed by the frequency of extracellular action potentials and spontaneous network-driven oscillations. These data support a more inhibitory role for GABA in the unperturbed immature brain, demonstrate the utility of the acute brain slice preparation for the study of the consequences of trauma, and provide potential mechanisms for both GABA-mediated excitatory network events in the slice preparation and early post-traumatic seizures.
Details
- Title: Subtitle
- Traumatic Alterations in GABA Signaling Disrupt Hippocampal Network Activity in the Developing Brain
- Creators
- Volodymyr Dzhala - Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114Guzel Valeeva - National Institute of Health and Medical Research, INSERM U-901, Marseille 13273, France, andJoseph Glykys - Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114Rustem Khazipov - National Institute of Health and Medical Research, INSERM U-901, Marseille 13273, France, andKevin Staley - Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.32(12), pp.4017-4031
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.5139-11.2012
- PMID
- 22442068
- PMCID
- PMC3333790
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 03/21/2012
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984015717902771
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