GABA Transporter-1 (GAT1) Deficient Differential Tonic Activation of G Mice: ABAA versus GABAB Receptors in the Hippocampus

tem (CNS), the (GATs). The predominant neuronal GABA transporter GAT1 is localized in GABAergic axons and nerve terminals, where it is thought to influence GABAergic synaptic transmission, but the details rain of GAT1 pocampal GABAAwaveform or amplitude y of quantal GABA release was one-third of WT, although the densities of GABAA-receptors, GABABt mice lacked a requency of ced extracellular on of GABAA-receptors responsible for a postsynaptic tonic conductance. Chronically elevated GABA levels also downregulate phasic GABA release and reduce presynaptic signaling via GABAB receptors thus causing an enhanced tonic and a diminished phasic inhibition. Following its release from interneurons in the central nervous sys major inhibitory neurotransmitter GABA is taken up by GABA transporters of this regulation are unclear. To address this issue, we have generated a st deficient mice. We observed a large increase in a tonic postsynaptic hip receptor mediated conductance. There was little or no change in the of spontaneous IPSCs or miniature IPSCs. In contrast, the frequenc receptors, GAD65 and VGAT1 were unaltered. The GAT1 deficien presynaptic GABAB-receptor tone, present in WT mice, which reduces the f spontaneous IPSCs. We conclude that GAT1 deficiency leads to enhan GABA levels resulting in an overactivati