GABAergic over-inhibition, a promising hypothesis for cognitive deficits in Down syndrome

GABAergic synapse in euploid and DS conditions: the number of GABAergic neurons and synapses is and the size of inhibitory synapses are increased in the DS condition. Levels of GABA at the synapse should be increase with more GABA spill-over. Overexpression of NKCC1 leads to higher intracellular chloride, hyper hyperpolarization and deactivation. Triplicated genes such as GIRK2 (decreases intracellular potassium concentrations inducing hyperpolarization after GABAB receptor activation) and DYRK1A (increases the number of GABAergic neurons and markers) could be involved.268