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

Abstract

Absence seizures (ASs) are associated with abnormalities in gamma-aminobutyric acid (GABA) neurotransmission in the thalamus and the cortex. In the present study, we used light microscopy GABA immunocytochemistry to quantify the GABA-immunoreactive (GABA-IR) neurons and neuropil in the thalamic ventral basal (VB) nucleus, the nucleus reticularis thalami (NRT), the dorsal lateral geniculate (dLGN), the primary motor cortex (M1) and perioral region of the somatosensory cortex (S1po) of genetic absence epilepsy rats from Strasbourg (GAERS). We used both the relative non-epileptic control (NEC) and normal Wistar rats as control strains, and investigated GABA immunostaining at postnatal day 15 (P15), P25, and P90. The main findings were i) an increase in GABA-IR neuropil in the VB at P25 and P90 in GAERS but not in NEC and Wistar rats; ii) an increase in NRT GABA-IR neurons in GAERS and NEC, but not Wistar, rats at both P25 and P90; and iii) an increase in GABA-IR neuron density in S1po of GAERS at P25 and P90 and in Wistar at P90. These results indicate that the increased GABAergic innervation in the VB at P25 most likely contributes to the enhanced tonic inhibition observed in GAERS prior to AS onset, whereas the lack of any anatomo-morphological GABAergic differences in GAERS S1po suggests that functional more than structural abnormalities underlie the origin of cortical paroxysms in S1po of this AS model.This article is part of the “Special Issue Dedicated to Norman G. Bowery”.

Sensory coding is impaired in rat absence epilepsy

“…However, the cellular migration of interneurons should be finished before the appearance of SWDs in GAERS (Wonders & Anderson, 2006), therefore suggesting that their increased density could rather participate, at least indirectly, in the initiation of SWD by promoting the pro-epileptogenic activities of high-frequency oscillations (Cardin et al 2009;Veit et al 2017). In this case, comorbidities associated with AE could partly result from the plasticity induced by seizure recurrence, as suggested recently (Bombardi et al 2018). If this hypothesis is confirmed in the clinic, it raises the need to detect and block absence seizures as soon as possible in patients.…”

“…Because PV+ and SOM+ interneurons are essential for sensory coding and gamma oscillation (Cardin et al 2009;Buzsáki & Wang, 2012;Veit et al 2017), an increased number of these interneurons could explain the augmented gamma power in GAERS that not only favours SWDs, but also may alter sensory coding. A recent study showed no difference in terms of GABA+ interneurons in the S1Bf of GAERS (Bombardi et al 2018). By contrast, another recent study showed an elevation of PV+ interneurons in the S1 cortex of GAERS that was not present in WAG/Rij (Papp et al 2018).…”

“…In this case, comorbidities associated with AE could partly result from the plasticity induced by seizure recurrence, as suggested recently (Bombardi et al . ). If this hypothesis is confirmed in the clinic, it raises the need to detect and block absence seizures as soon as possible in patients.…”

“…A recent study showed no difference in terms of GABA+ interneurons in the S1Bf of GAERS (Bombardi et al . ). By contrast, another recent study showed an elevation of PV+ interneurons in the S1 cortex of GAERS that was not present in WAG/Rij (Papp et al .…”

Fangjing decoction relieves febrile seizures-induced hippocampal neuron apoptosis in rats via regulating the Akt/mTOR pathway

“…Taken together, these data suggest that Fangjing decoction can ameliorate FS-induced cerebral injury through inhibiting neuronal apoptosis and controlling the Akt/m-TOR signaling pathway. As with other forms of epilepsy, dysfunctions in the brain GABA system are thought to have a crucial role in the pathogenesis of seizures [ 31 ]. In particular, many studies in human cohorts affected by seizures have highlighted potential abnormalities related to various genes coding for proteins of the GABAergic system, including transporters, synthetizing enzymes, and subunits of both GABA A and GABA B receptor subtypes [ 32 ].…”