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Aberrant GABAA receptor-mediated inhibition in cortico-thalamic networks of succinic semialdehyde dehydrogenase deficient mice

Errington, Adam Clarke, Gibson, K. Michael, Crunelli, Vincenzo and Cope, David William 2011. Aberrant GABAA receptor-mediated inhibition in cortico-thalamic networks of succinic semialdehyde dehydrogenase deficient mice. PLoS ONE 6 (4) , e19021. 10.1371/journal.pone.0019021

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Abstract

Aberrant γ-aminobutyric acid type A (GABAA) receptor-mediated inhibition in cortico-thalamic networks remains an attractive mechanism for typical absence seizure genesis. Using the whole-cell patch clamp technique we examined ‘phasic’ and ‘tonic’ GABAA inhibition in thalamocortical neurons of somatosensory (ventrobasal, VB) thalamus, nucleus reticularis thalami (NRT) neurons, and layer 5/6 pyramidal neurons of the somatosensory (barrel) cortex of succinic semialdehyde dehydrogenase (SSADH) knock-out (SSADH−/−) mice that replicate human SSADH deficiency and exhibit typical absence seizures. We found increased sIPSC frequency in both VB and NRT neurons and larger sIPSC amplitude in VB neurons of SSADH−/− mice compared to wild-type animals, demonstrating an increase in total phasic inhibition in thalamus of SSADH−/− mice. mIPSCs in both VB and NRT neurons were no different between genotypes, although there remained a trend toward more events in SSADH−/− mice. In cortical layer 5/6 pyramidal neurons, sIPSCs were fewer but larger in SSADH−/− mice, a feature retained by mIPSCs. Tonic currents were larger in both thalamocortical neurons and layer 5/6 pyramidal neurons from SSADH−/− mice compared to WTs. These data show that enhanced, rather than compromised, GABAA receptor-mediated inhibition occurs in cortico-thalamic networks of SSADH−/− mice. In agreement with previous studies, GABAA receptor-mediated inhibitory gain-of-function may be a common feature in models of typical absence seizures, and could be of pathological importance in patients with SSADH deficiency.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Neuroscience and Mental Health Research Institute (NMHRI)
Medicine
Subjects: Q Science > Q Science (General)
Publisher: PLoS
ISSN: 1932-6203
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 03:45
URI: http://orca.cf.ac.uk/id/eprint/26114

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