Astrocytic GABA transporter GAT-1 dysfunction in experimental absence seizures


H. R. Parri: School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK. Email:

V. Crunelli: Neuroscience Division, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK. Email:

Key points

  • Enhanced thalamic tonic GABA inhibition plays a role in experimental absence seizures.

  • In this study we investigated astrocytic GABA transporter function and gliotransmitter release in an absence seizure rat model.

  • GAT-1 GABA transporter currents in thalamic astrocytes were reduced in an absence seizure rat model.

  • Spontaneous phasic astrocytic GABA events displayed kinetic differences between absence seizure model rats and non-epileptic controls.

  • Spontaneous phasic astrocyte glutamate release was not different in absence seizure model rats and non-epileptic controls.

Abstract  An enhanced tonic GABAA inhibition in the thalamus plays a crucial role in experimental absence seizures and has been attributed, on the basis of indirect evidence, to a dysfunction of the astrocytic GABA transporter-1 (GAT-1). Here, the GABA transporter current was directly investigated in thalamic astrocytes from a well-established genetic model of absence seizures, the genetic absence epilepsy rats from Strasbourg (GAERS), and its non-epileptic control (NEC) strain. We also characterized the novel form of GABAergic and glutamatergic astrocyte-to-neuron signalling by recording slow outward currents (SOCs) and slow inward currents (SICs), respectively, in thalamocortical (TC) neurons of both strains. In patch-clamped astrocytes, the GABA transporter current was abolished by combined application of the selective GAT-1 and GAT-3 blocker, NO711 (30 μm) and SNAP5114 (60 μm), respectively, to GAERS and NEC thalamic slices. NO711 alone significantly reduced (41%) the transporter current in NEC, but had no effect in GAERS. SNAP5114 alone reduced by half the GABA transporter current in NEC, whilst it abolished it in GAERS. SIC properties did not differ between GAERS and NEC TC neurons, whilst moderate changes in SOC amplitude and kinetics were observed. These data provide the first direct demonstration of a malfunction of the astrocytic thalamic GAT-1 transporter in absence epilepsy and support an abnormal astrocytic modulation of thalamic ambient GABA levels. Moreover, while the glutamatergic astrocyte–neuron signalling is unaltered in the GAERS thalamus, the changes in some properties of the GABAergic astrocyte–neuron signalling in this epileptic strain may contribute to the generation of absence seizures.