2007 Fiscal Year Final Research Report Summary
The role of GABAAreceptors and inhibitory neuron network on anesthetic-induced neural inhibition
| Project/Area Number |
17390425
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Gunma University |
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Principal Investigator |
NISHIKAWA Koichi Gunma University, Graduate School of Medicine, Associate professor (00334110)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Synaptic transmission / GABA receptor / Plasticity / Anesthetics / Amnesia / Hypnosis / Patch clamp / Memory |
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| Research Abstract |
Background: The cellular mechanisms of anesthetic-induced amnesia are still poorly understood. The present study examined the effects of sevoflurane at various concentrations on excitatory synaptic transmission and on long-term potentiation (LTP) as a possible mechanism contributing to loss of recall in the CA1 region of rat hippocampal slices. Methods: Population spikes (PS) and field excitatory postsynaptic potentials (fEPSPs) were recorded using extracellular electrodes following electrical stimulation of Schaffer-collateral-commissural (SCC) fiber inputs. Paired pulse facilitation (PPF) was used as a measure of presynaptic effects of the anesthetic LTP was induced using tetanic stimulation (100 Hz, 1 s) of the SCC pathway. Sevoflurane at subanesthetic (0.5%) to anesthetic concentrations (28-5.0%) was applied to slices in artificial cerebrospinal fluid solution.
Results: In the presence of subanesthetic sevoflurane (0.5%), PS amplitude was significantly depressed and tetanic stimulation induced only post-tetanic potentiation (PTP) and then failure of LTP. These inhibitory effects were antagonized by bicuculline (10μM), a GABA_A receptor antagonist. In addition, anesthetic sevoflurane further depressed fEPSP amplitude in a dose-dependent manner, and completely blocked LTP. Bicuculline only partially antagonized anesthetic sevoflurane-induced profound inhibition of LTP. Anesthetic but not subanesthetic, sevoflurane significantly increased PPF, suggesting that anesthetic sevoflurane has presynaptic actions to reduce glutamate release from nerve terminals.
Conclusions: The present study provides evidence that subanesthetic sevoflurane inhibits long-term potentiation of hippocampal CA1 neurons through GABAergic mechanisms, and these actions alone seem to account for the effects of subanesthetic sevoflurane on synaptic plasticity.
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Research Products
(8 results)
