Aberrant GABAA Receptor-Mediated Inhibition in Cortico-Thalamic Networks of Succinic Semialdehyde Dehydrogenase Deficient Mice

Adam C Errington; K. Michael Gibson; Vincenzo Crunelli; David W Cope

doi:10.1371/journal.pone.0019021

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Aberrant GABAA Receptor-Mediated Inhibition in Cortico-Thalamic Networks of Succinic Semialdehyde Dehydrogenase Deficient Mice

Journal article

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Aberrant GABAA Receptor-Mediated Inhibition in Cortico-Thalamic Networks of Succinic Semialdehyde Dehydrogenase Deficient Mice

Adam C Errington, K. Michael Gibson, Vincenzo Crunelli and David W Cope

PloS one, Vol.6(4), p.e19021

2011

DOI: https://doi.org/10.1371/journal.pone.0019021

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https://hdl.handle.net/2376/106589

PMCID: PMC3079762

PMID: 21526163

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Abstract

Medicine

Biology

Aberrant γ-aminobutyric acid type A (GABA A ) 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’ GABA A 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, GABA A receptor-mediated inhibition occurs in cortico-thalamic networks of SSADH −/− mice. In agreement with previous studies, GABA A 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.

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Title: Aberrant GABAA Receptor-Mediated Inhibition in Cortico-Thalamic Networks of Succinic Semialdehyde Dehydrogenase Deficient Mice
Creators: Adam C Errington
K. Michael Gibson
Vincenzo Crunelli
David W Cope
Publication Details: PloS one, Vol.6(4), p.e19021
Academic Unit: Pharmacotherapy, Department of
Publisher: Public Library of Science; San Francisco, USA
Identifiers: 99900546745201842
Language: English
Resource Type: Journal article