FIGURE 8.

Summary cartoon illustrating the mechanism to counterbalance a temporal neuronal gamma-aminobutyric acid (GABA) deficit in KI mice at P14 through activation of tonic pre- and postsynaptic GABAB receptors (GABA_BRs) at glutamatergic synapses in the somatosensory cortex. (Left) Glutamatergic synapse of the somatosensory cortex in a wild-type (WT)-mouse at P14. GABA is taken up normally via GAT1 into GABAergic neurons (not shown) and via GABA transporter 3 (GAT-3) (orange) into astrocytes (purple). Subsequently, GABA_BRs (blue) are not activated. (Right) Glutamatergic synapse of the somatosensory cortex in a KI mice at P14. Astrocytes express the GAT-3 transporter, which is operating in reverse mode. The extrasynaptic GABA, released via GAT-3, can activate pre- and postsynaptic GABA_BRs. This activation of GABA_BRs leads to a decreased presynaptic glutamate release and decreased postsynaptic strength to counterbalance network activity, thereby preventing hyperexcitability in a GABA-deficient cortex (Figure created with Biorender.com).