Comparing GABAergic cell populations in the thalamic reticular nucleus of normal and genetic absence epilepsy rats from Strasbourg (GAERS)

Abstract

The GABAergic neurons of the thalamic reticular nucleus (TRN) play a critical role in the generation and control of spike-and-wave discharges (SWDs) in absence epilepsy. We have used the disector method to count the GABA+ve and GABA-ve neurons in the intermediate TRN sector of genetic absence epilepsy rats from Strasbourg (GAERS) and of Wistar rats during postnatal (P) development at P10, P20, P30, and P60 days. The same part of TRN was removed from each animal, the GABAergic neurons were labelled using light-microscopical GABA immunohistochemistry and the data were statistically analysed. Both the GAERS and Wistar animals showed an increase in the density of GABA+ve and GABA-ve cells from P10 to P20. From P20 to P60, Wistar animals showed no significant differences for either cell type, but in the GAERS a progressive decrease from P20 to P60 was observed in both GABA+ve and GABA-ve cells. The decrease of the GABA-ve cells was more pronounced than that of the GABA+ve cells. There were no significant differences between cell sizes for GAERS and Wistar rats at any developmental age. The lower density GABA+ve and GABA-ve neurons at P30 and P60 of GAERS compared to Wistar animals may contribute to the generation of SWDs in absence epilepsy.

Developmental changes of GABA immunoreactivity in cortico-thalamic networks of an absence seizure model

“…A developmental increase in the number of the GABA-IR neurons in GAERS and NEC, but not in the Wistar, NRT was observed in this study from P15 to P25-P90. Other authors have shown a similar increase at P10 to P20 in both Wistar and GAERS but a progressive decrease at P60 only in GAERS ( Cavdar et al., 2013 ), while a reduction in Wistar at both P90 and P720 in Wistar ( Ramos et al., 1995 ). As it does occur in both GAERS and NEC, it is unlikely that the increased density of NRT GABA-IR neurons in GAERS during development is related to the expression of the absence phenotype.…”

“…Three methodological issues should be considered before discussing the differences between our findings and those of previous studies in GAERS. First, we used a GABA monoclonal antibody whereas previous investigations in GAERS have employed polyclonal antibodies ( Cavdar et al., 2013 , Cavdar et al., 2014 , Cavdar et al., 2012 ). Second, different GAERS colonies, though all derived from the original strain in Strasbourg ( Depaulis et al., 2016 , Vergnes et al., 1987 ), show diverse AS phenotypes, potentially resulting from different lengths of inbreeding and environmental conditions at diverse establishments ( Powell et al., 2014 ).…”

“…As far as the anatomo-morphological features of GABAergic neurons in cortico-thalamic networks are concerned, a recent study has shown a higher proportion of GABAergic cells in the ventroposteromedial (VPM) and ventroposterolateral (VPL) thalamic nuclei, the two subdivision of the VB, in 6–12 month old GAERS than in age-matched normal Wistar rats ( Cavdar et al., 2014 ), in contrast to the accepted view that in this rodent thalamic nucleus GABAergic interneurons are only sparse or absent ( Arcelli et al., 1997 , Harris and Hendrickson, 1987 , Houser et al., 1980 ). Moreover, a developmental decrease in the number of NRT GABA-positive and GABA-negative neurons has been described in GAERS at postnatal day 30 (P30) to P60 compared to normal Wistar rats ( Cavdar et al., 2013 ), whereas GABA-immunoreactive (GABA-IR) profiles in the GAERS VB shows a 3-fold increase at the same postnatal ages compared to Wistar rats ( Cavdar et al., 2012 ). In the γ 2 R43Q mouse model, a higher density of various GABAergic interneurons has been reported in S1, though paradoxically the ratio between putative excitatory and inhibitory neurons was found to be decreased ( Wimmer et al., 2015 ).…”

Thalamic control of sensory enhancement and sleep spindle properties in a biophysical model of thalamoreticular microcircuitry

“…We chose the VPL nucleus because it receives information from the hindlimb (Joseph T Francis et al, 2008) and relays it to the somatosensory cortex; the corresponding cortical microcircuit was reconstructed in a previous model (Markram et al, 2015a). The Rt is intimately associated with the different thalamic nuclei and it is the primary source of inhibition to the thalamus (Cavdar et al, 2013; de Biasi et al, 1986; Houser et al, 1980; Pinault, 2004). Since the VPL does not have a clear modular organization, we followed a previously published approach to define the microcircuit radius and its height (Markram et al, 2015a).…”

Rodent Somatosensory Thalamocortical Circuitry: Neurons, Synapses, and Connectivity

“…Aside from the widely different proportions that have been reported in section 4.3, almost nothing is known about their electrophysiological properties, their connectivity, their morphologies, and their functional role. Also puzzling is the report of non-GABAergic neurons in Rt (Cavdar et al, 2013). Further, only a few paired-recording studies have investigated the inhibition between interneurons and TC cells comprehensively, with none reporting on the short-term plasticity dynamics of IPSP at the interneuron-TC synapse.…”