GABA transporter 1 tunes GABAergic synaptic transmission at output neurons of the mouse neostriatum
- 28 November 2008
- journal article
- Published by Wiley in The Journal of Physiology
- Vol. 586 (23), 5665-5678
- https://doi.org/10.1113/jphysiol.2008.161943
Abstract
GABAergic medium-sized striatal output neurons (SONs) provide the principal output for the neostriatum. In vitro and in vivo data indicate that spike discharge of SONs is tightly controlled by effective synaptic inhibition. Although phasic GABAergic transmission critically depends on ambient GABA levels, the role of GABA transporters (GATs) in neostriatal GABAergic synaptic transmission is largely unknown. In the present study we aimed at elucidating the role of GAT-1 in the developing mouse neostriatum (postnatal day (P) 7-34). We recorded GABAergic postsynaptic currents (PSCs) using the whole-cell patch-clamp technique. Based on the effects of NO-711, a specific GAT-1 blocker, we demonstrate that GAT-1 is operative at this age and influences GABAergic synaptic transmission by presynaptic and postsynaptic mechanisms. Presynaptic GABA(B)R-mediated suppression of GABA release was found to be functional at all ages tested; however, there was no evidence for persistent GABA(B)R activity under control conditions, unless GAT-1 was blocked (P12-34). In addition, whereas no tonic GABA(A)R-mediated conductances were detected in SONs until P14, application of a specific GABA(A)R antagonist caused distinct tonic outward currents later in development (P19-34). In the presence of NO-711, tonic GABA(A)R-mediated currents were also observed at P7-14 and were dramatically increased at more mature stages. Furthermore, GAT-1 block reduced the median amplitude of GABAergic miniature PSCs indicating a decrease in quantal size. We conclude that in the murine neostriatum GAT-1 operates in a net uptake mode. It prevents the persistent activation of presynaptic GABA(B)Rs (P12-34) and prevents (P7-14) or reduces (P19-34) tonic postsynaptic GABA(A)R activity.Keywords
This publication has 56 references indexed in Scilit:
- Cajal-Retzius cells in the mouse neocortex receive two types of pre- and postsynaptically distinct GABAergic inputsThe Journal of Physiology, 2007
- Feedforward and feedback inhibition in neostriatal GABAergic spiny neuronsBrain Research Reviews, 2007
- The Role of the Dorsal Striatum in Reward and Decision-Making: Figure 1.Journal of Neuroscience, 2007
- The main source of ambient GABA responsible for tonic inhibition in the mouse hippocampusThe Journal of Physiology, 2007
- Plasticity of rat central inhibitory synapses through GABA metabolismThe Journal of Physiology, 2001
- Differential expression of GABABR1 and GABABR2 receptor immunoreactivity in neurochemically identified neurons of the rat neostriatumJournal of Comparative Neurology, 2001
- Striatal interneurones: chemical, physiological and morphological characterizationTrends in Neurosciences, 1995
- Neuronal mechanism underlying dystonia induced by bicuculline injection into the putamen of the catBrain Research, 1995
- Excitatory Amino Acid-Evoked Release of ?-[3H]Aminobutyric Acid from Striatal Neurons in Primary CultureJournal of Neurochemistry, 1988
- Late development of intrinsic excitation in the rat neostriatum: an in vitro studyDevelopmental Brain Research, 1986