Do the quantitative relationships of synaptic junctions and terminals in the thalamus of genetic absence epilepsy rats from Strasbourg (GAERS) differ from those in normal control Wistar rats

Abstract

Abnormal functional properties of the thalamocortical connections were reported in the absence of epilepsy. The present study compares the ratios of terminals ('RL'-round vesicles, large terminals, 'RS'-round vesicles, small terminals and 'F'-flattened vesicles) and synapse in three first-order (ventrobasal, lateral geniculate and anteroventral) and in three higher-order (posterior, lateral posterior and mediodorsal) thalamic nuclei of genetic absence epilepsy rats from Strasbourg (GAERS) with our earlier quantitative studies of normal Wistar rats to show whether quantitative differences were present in GAERS as compared to Wistar rat. Rats were perfused transcardially, the brains were removed and cut as 300 μm coronal sections. Parts of the six thalamic nuclei were removed for routine electron microscopy and GABA immunocytochemistry. Twenty photographs from each section at 20,000× magnification were taken, and the terminals were identified as RL, RS or F. (1) In normal Wistar rats (as in cats), the proportion of driver terminals (RL) and synapses is lower in higher-order than in first-order thalamic nuclei, but this difference is not present in GAERS animals. (2) The proportions of RS terminals and synapses for each thalamic nucleus showed no significant differences between GAERS and Wistar rats for any of the thalamic nuclei. (3) In GAERS, the proportion of inhibitory F terminals and synapses was significantly high in the VB and low in the LP thalamic nucleus. These abnormal ratios in the GAERS may be the cause of the spike-and-wave discharges of absence seizures or may represent a compensatory response of the thalamocortical circuitry to the absence seizures.

Dynamics of networks during absence seizure's on- and offset in rodents and man

“…Indeed, the Po in GAERS contains a higher number of driver terminals, as compared to healthy non-epileptic control rats. This difference was not found in other thalamic nuclei (Cavdar et al, 2012 ). Furthermore, higher-order nuclei like the Po, as compared to first order nuclei such as the VPM, have been demonstrated to be more prone to thalamic burst firing (Ramcharan et al, 2005 ), a property which is generally believed to be favorable for SWD generation (Avoli et al, 2001 ).…”

Comparison of numbers of interneurons in three thalamic nuclei of normal and epileptic rats

“…in the Wistar rats and 19.2% in the GAERS [36,41] . This is in accord with the present results that an unexpectedly high number of GABAergic interneurons occurred in the VPM and VPL nuclei of the GAERS animals relative to the Wistar rats.…”

“…The measurements were made by an observer who was blinded LGN sample section was published in our previous manuscript [36] , for which the same tissue blocks were used.…”

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

“…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 ).…”