PMID- 11533137
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20190513
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 535
IP  - Pt 2
DP  - 2001 Sep 1
TI  - Plasticity of rat central inhibitory synapses through GABA metabolism.
PG  - 473-82
AB  - 1. The production of the central inhibitory transmitter GABA (gamma-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 gamma-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.
FAU - Engel, D
AU  - Engel D
AD  - Institut fur Physiologie der Charite, Humboldt-Universitat, Tucholskystrasse 2, 
      10117 Berlin, Germany.
FAU - Pahner, I
AU  - Pahner I
FAU - Schulze, K
AU  - Schulze K
FAU - Frahm, C
AU  - Frahm C
FAU - Jarry, H
AU  - Jarry H
FAU - Ahnert-Hilger, G
AU  - Ahnert-Hilger G
FAU - Draguhn, A
AU  - Draguhn A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Enzyme Inhibitors)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - B03TJ3QU9M (3-Mercaptopropionic Acid)
RN  - EC 2.6.1.19 (4-Aminobutyrate Transaminase)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - GR120KRT6K (Vigabatrin)
SB  - IM
MH  - 3-Mercaptopropionic Acid/pharmacology
MH  - 4-Aminobutyrate Transaminase/antagonists & inhibitors/metabolism
MH  - Animals
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Glutamate Decarboxylase/antagonists & inhibitors/metabolism
MH  - Hippocampus/metabolism
MH  - Male
MH  - Membrane Potentials/drug effects/physiology
MH  - Neural Inhibition/*physiology
MH  - Neuronal Plasticity/*physiology
MH  - Patch-Clamp Techniques
MH  - Rats
MH  - Rats, Wistar
MH  - Synapses/*metabolism
MH  - Vigabatrin/pharmacology
MH  - gamma-Aminobutyric Acid/biosynthesis/*metabolism
PMC - PMC2278801
EDAT- 2001/09/05 10:00
MHDA- 2002/01/05 10:01
PMCR- 2002/09/01
CRDT- 2001/09/05 10:00
PHST- 2001/09/05 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/09/05 10:00 [entrez]
PHST- 2002/09/01 00:00 [pmc-release]
AID - PHY_12139 [pii]
AID - 10.1111/j.1469-7793.2001.00473.x [doi]
PST - ppublish
SO  - J Physiol. 2001 Sep 1;535(Pt 2):473-82. doi: 10.1111/j.1469-7793.2001.00473.x.