Blockade of GABA Transporter (GAT-1) Modulates the GABAergic Transmission in the Rat Globus Pallidus

  • Xiao-Tao Jin
  • Jean-Francois Paré
  • Yoland Smith
Conference paper
Part of the Advances in Behavioral Biology book series (ABBI, volume 58)


Previous studies from our laboratory have demonstrated that application of SKF 89976A, a selective inhibitor of the GABA transporter GAT-1, reduces the activity of pallidal neurons in monkeys. However, the functional role of GAT-1 on GABAergic synaptic transmission in the globus pallidus (GP) is poorly understood. In the present study, we applied the whole-cell patch clamp recording technique to study the effects of blockade of GAT-1 on GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) recorded from rat GP slice preparations. Under maximal striatal stimulation (15–20 V) in parasagittal slices, SKF 89976A (10 μM) significantly prolonged the decay time, without significant effect on the amplitude, of IPSC. In contrast, SKF 89976A increased the amplitude, but did not prolong the decay time, of IPSCs under minimal striatal stimulation (2–5 V). We did not find any significant effect of SKF 89976A on IPSCs evoked locally from GP coronal slices. Furthermore, neither the amplitude nor the frequency of miniature IPSCs were changed following bath application of SKF 89976A. These results demonstrate that GABA reuptake through GAT-1 plays a major activity-dependent role in regulating GABAergic transmission at striatopallidal synapses in the GP.


Globus Pallidus Bath Application GABAergic Transmission Gaba Transporter Inhibitory Postsynaptic Current 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by a grant from NIH to YS (R01 NS 042937) and the Yerkes base grant (RR00165).


  1. Bevan MD, Booth PA, Eaton SA and Bolam JP (1998) Selective innervation of neostriatal interneurons by a subclass of neuron in the globus pallidus of the rat. J Neurosci 18: 9438–9452.PubMedGoogle Scholar
  2. Bevan MD, Magill P, Terman D, Bolam JP and Wilson CJ (2002) Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network. Trends Neurosci 25: 525–531.CrossRefPubMedGoogle Scholar
  3. Borden LA (1996) GABA transporter heterogeneity: pharmacology and cellular localization. Neurochem Int 29: 335–356.CrossRefPubMedGoogle Scholar
  4. Chen L and Yung WH (2003) Effects of the GABA-uptake inhibitor tiagabine in rat globus pallidus. Exp Brain Res 152: 263–269.CrossRefPubMedGoogle Scholar
  5. Draguhn A and Heinemann U (1996) Different mechanisms regulate IPSC kinetics in early postnatal and juvenile hippocampal granule cells. J Neurophysiol 76: 3983–3993.PubMedGoogle Scholar
  6. Galvan A, Villalba RM, West SM, Maidment NT, Ackerson LC, Smith Y and Wichmann T (2005) GABAergic modulation of the activity of globus pallidus neurons in primates: in vivo analysis of the functions of GABA receptors and GABA transporters. J Neurophysiol 94: 990–1000.CrossRefPubMedGoogle Scholar
  7. Isaacson JS, Solis JM and Nicoll RA (1993) Local and diffuse synaptic actions of GABA in the hippocampus. Neuron 10: 165–175.CrossRefPubMedGoogle Scholar
  8. Jensen K, Chiu CS, Sokolova I, Lester HA and Mody I (2003) GABA transporter-1 (GAT1)-deficient mice: differential tonic activation of GABAA versus GABAB receptors in the hippocampus. J Neurophysiol 90: 2696–2701.Google Scholar
  9. Jin XT, Pare JF, Raju DV and Smith Y (2006) Localization and function of pre- and postsynaptic kainate receptors in the rat globus pallidus. Eur J Neurosci 23: 374–386.CrossRefPubMedGoogle Scholar
  10. Jin XT and Smith Y (2007) Activation of presynaptic kainate receptors suppresses GABAergic synaptic transmission in the rat globus pallidus. Neuroscience 149: 338–349.CrossRefPubMedGoogle Scholar
  11. Kawaguchi Y, Wilson CJ and Emson PC (1990) Projection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin. J Neurosci 10: 3421–3438.PubMedGoogle Scholar
  12. Keros S and Hablitz JJ (2005) Subtype-specific GABA transporter antagonists synergistically modulate phasic and tonic GABAA conductances in rat neocortex. J Neurophysiol 94: 2073–2085.CrossRefPubMedGoogle Scholar
  13. Kita H and Kitai ST (1991) Intracellular study of rat globus pallidus neurons: membrane properties and responses to neostriatal, subthalamic and nigral stimulation. Brain Res 564: 296–305.CrossRefPubMedGoogle Scholar
  14. Kita H and Kita T (2001) Number, origins, and chemical types of rat pallidostriatal projection neurons. J Comp Neurol 437: 438–448.CrossRefPubMedGoogle Scholar
  15. Kita H, Tokuno H and Nambu A (1999) Monkey globus pallidus external segment neurons projecting to the neostriatum. NeuroReport 10: 1467–1472.CrossRefPubMedGoogle Scholar
  16. Oorschot DE (1996) Total number of neurons in the neostriatal, pallidal, subthalamic, and substantia nigral nuclei of the rat basal ganglia: a stereological study using the cavalieri and optical disector methods. J Comp Neurol 366: 580–599.CrossRefPubMedGoogle Scholar
  17. Overstreet LS, Jones MV and Westbrook GL (2000) Slow desensitization regulate the availability of synaptic GABAA receptors. J Neurosci 20: 7914–7921.PubMedGoogle Scholar
  18. Overstreet LS and Westbrook GL (2003) Synapse density regulates independence at unitary inhibitory synapses. J Neurosci 23: 2618–2626.PubMedGoogle Scholar
  19. Parent A, Charara A and Pinault D (1995) Single striatofugal axons arborizing in both pallidal segments and in the substantia nigra in primates. Brain Res 698: 280–284.CrossRefPubMedGoogle Scholar
  20. Peters A, Palay SL and Webster HF (1991) The Fine Structure of the Nervous System: Neurons and Their Supporting Cells (3rd edition). New York: Oxford Press.Google Scholar
  21. Plenz D and Kitai ST (1999) A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus. Nature 400: 677–682.CrossRefPubMedGoogle Scholar
  22. Roepstorff A and Lambert JD (1992) Comparison of the effect of the GABA uptake blockers, tiagabine and nipecotic acid, on inhibitory synaptic efficacy in hippocampal CA1 neurons. Neurosci Lett 146: 131–134.CrossRefPubMedGoogle Scholar
  23. Roepstorff A and Lambert JD (1994) Factors contributing to the decay of the stimulus-evoked IPSC in rat hippocampal CA1 neurons. J Neurophysiol 72: 2911–2926.PubMedGoogle Scholar
  24. Sadek AR, Magill PJ and Bolam JP (2005) Local connectivity between neurons of the globus pallidus. In: The Basal Ganglia VIII. Bolam JP, Ingham CA and Magill PJ (eds). New York: Springer, pp 611–619.CrossRefGoogle Scholar
  25. Sadek AR, Magill PJ and Polam JP (2007) A single-cell analysis of intrinsic connectivity in the rat globus pallidus. J Neurosci 27: 6352–6362.CrossRefPubMedGoogle Scholar
  26. Smith Y, Bevan MD, Shink E and Bolam JP (1998) Microcircuitry of the direct and indirect pathways of the basal ganglia. Neuroscience 86: 353–387.CrossRefPubMedGoogle Scholar
  27. Thompson SM and Gähwiler BH (1992) Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures. J Neurophysiol 67: 1698–1701.PubMedGoogle Scholar
  28. Vivar C and Gutiérrez R (2005) Blockade of the membranal GABA transporter potentiates GABAergic responses evoked in pyramidal cells by mossy fiber activation after seizures. Hippocampus 15: 281–284.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Xiao-Tao Jin
    • 1
  • Jean-Francois Paré
    • 1
  • Yoland Smith
    • 1
  1. 1.Division of Neuroscience, Yerkes National Primate Research Center and Department of NeurologyEmory UniversityAtlantaUSA

Personalised recommendations