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”.
Highlights
Absence seizures (ASs) are a form of genetic generalized nonconvulsive seizures that involve brief impairment of consciousness, occasional myoclonic jerks of the eyes and peri-oral automatisms, and spike-and-wave discharges (SWDs) in the EEG which result from paroxysmal oscillations within cortico-thalamic networks (Blumenfeld, 2005; Crunelli and Leresche, 2002)
The main findings were i) an increase in GABA-IR neuropil in the ventrobasal thalamic nucleus (VB) at P25 and P90 in Generalized Absence Epilepsy Rats from Strasbourg (GAERS) but not in non-epileptic control (NEC) and Wistar rats; ii) an increase in Nucleus reticularis thalami (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
GABA-IR neurons located in VB, dorsal lateral geniculate nucleus (dLGN), S1po and M1 were small, had a multipolar or fusiform shape (Fig. 1AeC) as previously described for interneurons in these different areas (Amadeo et al, 2001; Arcelli et al, 1997; Barbaresi et al, 1986; Harris and Hendrickson, 1987; Spreafico et al, 1994)
Summary
Absence seizures (ASs) are a form of genetic generalized nonconvulsive seizures that involve brief impairment of consciousness, occasional myoclonic jerks of the eyes and peri-oral automatisms, and spike-and-wave discharges (SWDs) in the EEG which result from paroxysmal oscillations within cortico-thalamic networks (Blumenfeld, 2005; Crunelli and Leresche, 2002). C. Bombardi et al / Neuropharmacology 136 (2018) 56e67 currents are altered in the thalamic reticular neurons (NRT), but not in the VB or layer 2/3 cortical neurons of Generalized Absence Epilepsy Rats from Strasbourg (GAERS), a genetic model of ASs, compared to their non-epileptic control (NEC) strain (Bessaïh et al, 2006). We employed light microscopy GABA immunocytochemistry to quantify in GAERS the developmental profile of GABAergic neurons and GABA-IR profiles in the neuropil under the same experimental conditions in S1po, VB and NRT, three key regions involved in the paroxysmal oscillations that underlie ASs. We selected P15 (i.e., two days before tonic GABAA inhibition starts to increase in the VB (Cope et al, 2009)), P25 (i.e., a time when fullblown ASs start to occur in GAERS), and P90 (a time when all GAERS have experienced at least 2 months of continuous ASs). The GAERS data were compared to those obtained in the same brain regions of both normal Wistar rats and NEC, the Wistar-derived strain that is completely devoid of ASs (Vergnes et al, 1987)
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