Mechanisms underlying LTP of inhibitory synaptic transmission in the deep cerebellar nuclei
Mechanisms underlying LTP of inhibitory synaptic transmission in the deep cerebellar nuclei
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DOI：
10.1152/jn.2000.84.3.1414
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发表时间：
2000-09-01
影响因子：
2.5
通讯作者：
Sastry, BR
中科院分区：
文献类型：
--
作者：
Ouardouz, M;Sastry, BR
采用全细胞记录技术研究脑片小脑深核(DCN)神经元抑制性突触电流(IPSCs)的长时程增强效应。在非N-甲基-D-天冬氨酸(Non-NMDA)谷氨酸受体拮抗剂6，7-二硝基-2，3-二酮(20 MM)存在下，电刺激DCN周围白质诱发IPSCs。高频刺激引起IPSC波幅的长时程化(LTP)，但不改变其反转电位、上升时间和衰减时间常数。这种LTP不需要突触后γ-氨基丁酸-A(GABA(A))受体的激活，而依赖于NMDA受体的激活。DCN神经元中IPSCs的LTP也可以被突触后神经元的电压去极化脉冲所诱导，并且这种LTP似乎依赖于细胞内钙离子的增加，因为细胞内的LTP在钙离子螯合剂1，2-二(2-氨基苯氧基)-N，N，N‘，N’-四乙酸(BAPTA，10 mM)作用下被阻断。IPSCs的LTP伴随着自发IPSCs和微型IPSCs频率的增加(在河豚毒素1 mM存在下记录)，但其幅度没有显著变化。此外，在长时程增强过程中，外源性应用GABA(A)受体激动剂4，5，6，7-tetrahydroisoxazolo[5，4-c]pyridin-3-ol盐酸盐的反应幅度增加。DCN神经元细胞内应用破伤风毒素可阻止IPSCs LTP的诱导。我们的结果提示，DCN神经元中IPSCs LTP的诱导可能涉及突触后部位。DCN神经元抑制性突触传递的可塑性可能在小脑对运动协调和学习的控制中起关键作用。
Whole-cell recordings were used to investigate long-term potentiation of inhibitory synaptic currents (IPSCs) in neurons of deep cerebellar nuclei (DCN) in slices. IPSCs were evoked by electrical stimulation of the white matter surrounding the DCN in the presence of non-N-methyl-D-aspartate (non-NMDA) glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (20 mu M). High-frequency stimulation induced a long-term potentation (LTP) of the IPSC amplitude without changing its reversal potential, rise time, and decay-time constant. This LTP did not require the activation of postsynaptic gamma-aminobutyric acid-A (GABA(A)) receptors but depended on the activation of NMDA receptors. LTP of IPSCs in DCN neurons could also be induced by voltage-depolarizing pulses in postsynaptic neurons and appeared to depend on an increase in intracellular calcium as the LTP was blocked when the cells were loaded with a calcium chelator, 1,2-bis-(2-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA, 10 mM). LTP of IPSCs was accompanied by an increase in the frequency of spontaneous IPSCs and miniature IPSCs (recorded in the presence of tetrodotoxin 1 mM), but there was no significant change in their amplitude. In addition, during the LTP, the amplitude of response to exogenously applied GABA(A) receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride was increased. Intracellular application of tetanus toxin, a powerful blocker of exocytosis, in DCN neuron prevented the induction of LTP of IPSCs. Our results suggest that the induction of LTP of IPSCs in the DCN neurons likely involves a postsynaptic locus. Plasticity of inhibitory synaptic transmission in DCN neurons may play a crucial role in cerebellar control of motor coordination and learning.