Nucleus-specific abnormalities of GABAergic synaptic transmission in a genetic model of absence seizures

Bessaih, T., Bourgeais, L., Badiu, C. I., Carter, David Allan, Toth, T. I., Ruano, D., Lambolez, B., Crunelli, Vincenzo ORCID: https://orcid.org/0000-0001-7154-9752 and Leresche, N. 2006. Nucleus-specific abnormalities of GABAergic synaptic transmission in a genetic model of absence seizures. Journal of Neurophysiology 96 (6) , pp. 3074-3081. 10.1152/jn.00682.2006

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Abstract

Human and experimental studies indicate that molecular genetic changes in GABAA receptors may underlie the expression of spike-and-waves discharges (SWDs) occurring during absence seizures. However, the full spectrum of the genetic defects underlying these seizures has only been partially elucidated, the expression and functional profiles of putative abnormal protein(s) within the thalamocortical network are undefined, and the pathophysiological mechanism(s) by which these proteins would lead to absence paroxysms are poorly understood. Here we investigated GABAA inhibitory postsynaptic currents (IPSCs) in key thalamocortical areas, i.e., the somatosensory cortex, ventrobasal thalamus (VB) and nucleus reticularis thalami (NRT), in preseizure genetic absence epilepsy rats from Strasbourg (GAERS), a well-established genetic model of typical absence seizures that shows no additional neurological abnormalities, and compared their properties to age-matched non-epileptic controls (NECs). Miniature GABAA IPSCs of VB and cortical layers II/III neurons were similar in GAERS and NEC, whereas in GAERS NRT neurons they had 25% larger amplitude, 40% faster decay. In addition, baclofen was significantly less effective in decreasing the frequency of NRT mIPSCs in GAERS than in NEC, whereas no difference was observed for cortical and VB mIPSCS between the two strains. Paired-pulse depression was 45% smaller in GAERS NRT, but not in VB, and was insensitive to GABAB antagonists. These results point to subtle, nucleus-specific, GABAA receptor abnormalities underlying SWDs of typical absence seizures rather than a full block of these receptors across the whole thalamocortical network, and their occurrence prior to seizure onset suggests that they might be of epileptogenic significance.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Neuroscience and Mental Health Research Institute (NMHRI)
Publisher:	American Physiological Society
ISSN:	0022-3077
Last Modified:	27 Oct 2022 08:26
URI:	https://orca.cardiff.ac.uk/id/eprint/62338

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