Abstract
GABA transporter type 1 and 3 (GAT-1 and GAT-3, respectively) are the two main subtypes of GATs responsible for the regulation of extracellular GABA levels in the central nervous system. These transporters are widely expressed in neuronal (mainly GAT-1) and glial (mainly GAT-3) elements throughout the brain, but most data obtained so far relate to their role in the regulation of GABAA receptor-mediated postsynaptic tonic and phasic inhibition in the hippocampus, cerebral cortex and cerebellum. Taking into consideration the key role of GABAergic transmission within basal ganglia networks, and the importance for these systems to be properly balanced to mediate normal basal ganglia function, we analyzed in detail the localization and function of GAT-1 and GAT-3 in the globus pallidus of normal and Parkinsonian animals, in order to further understand the substrate and possible mechanisms by which GABA transporters may regulate basal ganglia outflow, and may become relevant targets for new therapeutic approaches for the treatment of basal ganglia-related disorders. In this review, we describe the general features of GATs in the basal ganglia, and give a detailed account of recent evidence that GAT-1 and GAT-3 regulation can have a major impact on the firing rate and pattern of basal ganglia neurons through pre- and post-synaptic GABAA- and GABAB-receptor-mediated effects.
Highlights
GABA is the main neurotransmitter used in the basal ganglia network, and abnormal transmission at specific GABAergic synapses underlies some of the pathophysiological features of various basal ganglia diseases
It is rather focused on the presentation of recent findings that have been gathered about these transporters in specific basal ganglia nuclei, and their potential importance for basal ganglia function and dysfunction
While there is compelling evidence that GABA transporters (GATs)-1 regulates GABAergic transmission in the hippocampus (Thompson and Gähwiler, 1992; Isaacson et al, 1993; Draguhn and Heinemann, 1996; Engel et al, 1998; Nusser and Mody, 2002; Overstreet and Westbrook, 2003; Semyanov et al, 2003), cerebral cortex (Keros and Hablitz, 2005; Bragina et al, 2008; Gonzalez-Burgos et al, 2009), and cerebellum (Rossi et al, 2003), much less is known about the functional role of GAT-1 in the basal ganglia (Rossi et al, 2003; Galvan et al, 2005; Kinney, 2005; Kirmse et al, 2009)
Summary
GABA is the main neurotransmitter used in the basal ganglia network, and abnormal transmission at specific GABAergic synapses underlies some of the pathophysiological features of various basal ganglia diseases. While there is compelling evidence that GAT-1 regulates GABAergic transmission in the hippocampus (Thompson and Gähwiler, 1992; Isaacson et al, 1993; Draguhn and Heinemann, 1996; Engel et al, 1998; Nusser and Mody, 2002; Overstreet and Westbrook, 2003; Semyanov et al, 2003), cerebral cortex (Keros and Hablitz, 2005; Bragina et al, 2008; Gonzalez-Burgos et al, 2009), and cerebellum (Rossi et al, 2003), much less is known about the functional role of GAT-1 in the basal ganglia (Rossi et al, 2003; Galvan et al, 2005; Kinney, 2005; Kirmse et al, 2009).
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