Postsynaptic mechanisms underlying long-term depression of GABAergic transmission in neurons of the deep cerebellar nuclei
Postsynaptic mechanisms underlying long-term depression of GABAergic transmission in neurons of the deep cerebellar nuclei
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DOI：
10.1152/jn.1996.76.1.59
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发表时间：
1996-07-01
影响因子：
2.5
通讯作者：
Sastry, BR
中科院分区：
文献类型：
--
作者：
Morishita, W;Sastry, BR
1.采用穿孔和全细胞电压钳技术，研究了10 Hz刺激抑制性传入神经引起的GABA（A）受体介导的突触传递长时程抑制（LTD）的机制.在电流钳条件下给予10-Hz刺激，使突触后神经元膜去极化，可可靠地诱导抑制性突触后电流（IPSC）的LTD.局部应用GABA（A）受体激动剂4，5，6，7-四氢异恶唑并[5，4-c]吡啶-3-醇盐酸盐（THIP）引起的电流也在LTD期间受到抑制。在10-Hz刺激下，LTD可以通过异突触方式诱导，不需要GABA（A）受体的激活.在用QX-314加载并用含有6-氰基-7-硝基喹喔啉-2，3-二酮（CNQX）和2-氨基-5-膦酰基戊酸（APV）的培养基灌流的细胞中，一系列去极化脉冲（50 mV，200 ms）诱导IPSC的持续抑制。然而，在用含有高双-（邻氨基苯氧基）-N，N，N '，N'-四乙酸（BAPTA）的移液器溶液记录的细胞中或当它们暴露于L型Ca 2+通道拮抗剂尼群地平时，未观察到这一点。10-Hz诱导的LTD也被BAPTA抑制，并且当DCN细胞负载微囊藻毒素LR或用蛋白磷酸酶抑制剂冈田酸处理时显著降低.这些结果表明，突触后[Ca ~（2+）]和磷酸酶活性的增加可以降低GABA（A）受体介导的突触传递的功效。
1. The mechanisms underlying long-term depression (LTD) of gamma-aminobutyric acid-A (GABA(A)) receptor-mediated synaptic transmission induced by 10-Hz stimulation of the inhibitory afferents were investigated using perforated and whole cell voltage-clamp recordings from neurons of the deep cerebellar nuclei (DCN).2. LTD of inhibitory postsynaptic currents (IPSCs) was reliably induced when the 10-Hz stimulation was delivered under current-clamp conditions where the postsynaptic neuronal membrane was allowed to depolarize.3. Currents elicited by local applications of the GABA(A) receptor agonist, 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol hydrochloride (THIP) were also depressed during LTD.4. LTD could be induced heterosynaptically and did not require the activation of GABA(A) receptors during the 10-Hz stimulation.5. In cells loaded with QX-314 and superfused with media containing 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonovaleric acid (APV), a series of depolarizing pulses (50 mV, 200 ms) induced a sustained depression of the IPSC. However, this was not observed in cells recorded with high bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)-containing pipette solutions or when they were exposed to the L-type Ca2+ channel antagonist, nitrendipine.6. The 10-Hz-induced LTD was also inhibited by BAPTA and was significantly reduced when DCN cells were loaded with microcystin LR or treated with okadaic acid, both inhibitors of protein phosphatases.7. These results indicate that increases in postsynaptic [Ca2+] and phosphatase activity can reduce the efficacy of GABA(A) receptor-mediated synaptic transmission.