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Plasticity of rat central inhibitory synapses through GABA metabolism
Author(s) -
Engel Dominique,
Pahner Ingrid,
Schulze Katrin,
Frahm Christiane,
Jarry Hubertus,
AhnertHilger Gudrun,
Draguhn Andreas
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.00473.x
Subject(s) - inhibitory postsynaptic potential , neuroscience , plasticity , chemistry , biology , physics , thermodynamics
1 The production of the central inhibitory transmitter GABA (γ‐aminobutyric acid) varies in response to different patterns of activity. It therefore seems possible that GABA metabolism can determine inhibitory synaptic strength and that presynaptic GABA content is a regulated parameter for synaptic plasticity. 2 We altered presynaptic GABA metabolism in cultured rat hippocampal slices using pharmacological tools. Degradation of GABA by GABA‐transaminase (GABA‐T) was blocked by γ‐vinyl‐GABA (GVG) and synthesis of GABA through glutamate decarboxylase (GAD) was suppressed with 3‐mercaptopropionic acid (MPA). We measured miniature GABAergic postsynaptic currents (mIPSCs) in CA3 pyramidal cells using the whole‐cell patch clamp technique. 3 Elevated intra‐synaptic GABA levels after block of GABA‐T resulted in increased mIPSC amplitude and frequency. In addition, tonic GABAergic background noise was enhanced by GVG. Electron micrographs from inhibitory synapses identified by immunogold staining for GABA confirmed the enhanced GABA content but revealed no further morphological alterations. 4 The suppression of GABA synthesis by MPA had opposite functional consequences: mIPSC amplitude and frequency decreased and current noise was reduced compared with control. However, we were unable to demonstrate the decreased GABA content in biochemical analyses of whole slices or in electron micrographs. 5 We conclude that the transmitter content of GABAergic vesicles is variable and that postsynaptic receptors are usually not saturated, leaving room for up‐regulation of inhibitory synaptic strength. Our data reveal a new mechanism of plasticity at central inhibitory synapses and provide a rationale for the activity‐dependent regulation of GABA synthesis in mammals.