Increased network activity induces tonic inhibition by emerging a glial GABA pool
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1
Hungarian Academy of Sciences, Department of Neurochemistry, Hungary
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2
Semmelweis University and Hungarian Academy of Sciences, Hungary
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3
Hungarian Academy of Sciences, Department of Pharmacobiochemistry, Hungary
Maintenance of the balance between excitation and inhibition is of crucial importance in the brain. Increasing evidence suggest that astroglial glutamate/Na+ symporters induce the reverse action of extrasynaptic astroglial γ-amino-butyric acid/Na+ symporter subtypes GAT-2 and GAT-3, generating tonic inhibition in neurons. The source of the released γ-amino-butyric acid (GABA), however, is uncertain, because GABA is synthesized mainly in neurons from Glu by the enzyme Glu decarboxylase. Here we show that an alternative pathway for the GABA synthetic route exists in astrocytes and this pathway is responsible for the synthesis of the released GABA. We used in vitro hippocampal slices under low-[Mg2+] conditions to measure GABA currents by whole cell patch clamp method in the absence and presence of SNAP-5114, a non-transportable blocker of GAT-2/3. Under control conditions SNAP-5114 application reveals the GAT-2/3 mediated tonic current component. Incubation of the slices with monoamine and diamine oxidase inhibitors (deprenyl and aminoguanidine, respectively) that prevent GABA formation from putrescine eliminated this tonic current component, demonstrating that under low-[Mg2+] conditions astrocytes utilize the polyamine pathway to synthesize GABA for maintaining tonic inhibition. We envision that the discovery of this mechanism will support the development of new pathomechanism-specific treatments for pathological conditions characterized by sustained excitation.
Keywords:
Neurophysiology,
Neuroscience
Conference:
13th Conference of the Hungarian Neuroscience Society (MITT), Budapest, Hungary, 20 Jan - 22 Jan, 2011.
Presentation Type:
Abstract
Topic:
Neurophysiology
Citation:
Kékesi
O,
Héja
L,
Nyitrai
G,
Dobolyi
Á,
Szabó
P,
Palkovits
M and
Kardos
J
(2011). Increased network activity induces tonic inhibition by emerging a glial GABA pool.
Front. Neurosci.
Conference Abstract:
13th Conference of the Hungarian Neuroscience Society (MITT).
doi: 10.3389/conf.fnins.2011.84.00152
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Received:
03 Mar 2011;
Published Online:
23 Mar 2011.
*
Correspondence:
Dr. O. Kékesi, Hungarian Academy of Sciences, Department of Neurochemistry, Budapest, Hungary, kekesi.orsolya@chemres.hu