PDF(Pubmed)
Abstract：
Pharmacologically-induced persistent hippocampal γ oscillation in area CA3 requires activation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs). However, we demonstrated that exogenous AMPA dose-dependently inhibited carbachol (CCH)-induced γ oscillation in the CA3 area of rat hippocampal slices, but the underlying mechanism is not clear. Application of AMPARs antagonist NBQX (1 μM) did not affect γ oscillation power (γ power), nor AMPA-mediated γ power reduction. At 3 μM, NBQX had no effect on γ power but largely blocked AMPA-mediated γ power reduction. Ca2+-permeable AMPA receptor (CP-AMPAR) antagonist IEM1460 or CaMKK inhibitor STO-609 but not CaMKIIα inhibitor KN93 enhanced γ power, indicating that activation of CP-AMPAR or CaMKK negatively modulated CCH-induced γ oscillation. Either CP-AMPAR antagonist or CaMKK inhibitor alone did not affected AMPA-mediated γ power reduction, but co-administration of IEM1460 and NBQX (1 μM) largely prevented AMPA-mediated downregulation of γ suggesting that CP-AMPARs and CI-AMPARs are involved in AMPA downregulation of γ oscillation. The recurrent excitation recorded at CA3 stratum pyramidale was significantly reduced by AMPA application. Our results indicate that AMPA downregulation of γ oscillation may be related to the reduced recurrent excitation within CA3 local neuronal network due to rapid CI-AMPAR and CP-AMPAR activation.
摘要：
CA3区域的药理学诱导的持续海马γ振荡需要激活α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯受体（AMPAR）。然而,我们证明了外源性AMPA剂量依赖性地抑制了卡巴胆碱（CCH）诱导的大鼠海马切片CA3区的γ振荡，但是潜在的机制尚不清楚。应用AMPARs拮抗剂NBQX（1μM）不影响γ振荡功率（γ功率），也不是AMPA介导的γ功率降低。在3μM时，NBQX对γ功率没有影响，但在很大程度上阻断了AMPA介导的γ功率降低。Ca2+通透性AMPA受体（CP-AMPAR）拮抗剂IEM1460或CaMKK抑制剂STO-609而不是CaMKIIα抑制剂KN93增强γ功率，表明CP-AMPAR或CaMKK的激活负调制CCH诱导的γ振荡。单独使用CP-AMPAR拮抗剂或CaMKK抑制剂均不影响AMPA介导的γ功率降低，但是IEM1460和NBQX（1μM）的共同给药在很大程度上阻止了AMPA介导的γ下调，这表明CP-AMPAR和CI-AMPAR参与了AMPA对γ振荡的下调。通过应用AMPA，在CA3层pyramidale记录的反复激发显着降低。我们的结果表明，由于rapidCI-AMPAR和CP-AMPAR激活，AMPA下调γ振荡可能与CA3局部神经元网络中反复激发的减少有关。
