Input-specific targeting of NMDA receptor subtypes at mouse hippocampal CA3 pyramidal neuron synapses

Input-specific targeting of NMDA receptor subtypes at mouse hippocampal CA3 pyramidal neuron synapses
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DOI:
10.1016/s0028-3908(99)00217-8
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发表时间:
2000-01-01
期刊:
影响因子:
4.7
通讯作者:
Sugiyama, H
Sugiyama, H
中科院分区:
医学2区
文献类型:
--
作者:
Ito, I;Kawakami, R;Sugiyama, H

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海马CA 3锥体神经元接受来自顶端和基底树突上的连合和联合纤维的突触输入。在野生型小鼠和GluR β 1(NR 2A)亚基敲除小鼠的海马切片中检查这些突触处的NMDA受体。电刺激CA 3辐射层或定向层激活连合和联合(C/A)突触,而刺激腹侧伞主要激活连合突触。Ro 25-6981和艾芬地尔(GluR epsilon 2(NR 2B)亚基选择性NMDA受体拮抗剂)比C/A-CA 3突触更强烈地抑制基底树突上连合-CA 3突触处的NMDA受体介导的兴奋性突触后电流(NMDA EPSC)。顶或基底树突上的CA 3突触。然而,谷氨酸诱发的NMDA受体电流减少的GluR β 1亚基敲除到一个类似的程度,在顶端和基底树突。GluR β 1亚基敲除也降低了基底树突上C/A-CA 3突触的NMDA EPSC,但不影响基底树突上连合-CA 3突触的NMDA EPSC。这些结果证实了我们以前的发现,即在不同的突触在CA 3锥体细胞的NMDA受体有不同的GluR β亚基组成,并进一步表明,GluR β亚基组成可能会受到调节,根据突触输入的类型,甚至在一个单一的CA 3锥体神经元。(C)2000爱思唯尔科技有限公司版权所有。
Hippocampal CA3 pyramidal neurons receive synaptic inputs from commissural and associational fibers on both apical and basal dendrites. NMDA receptors at these synapses were examined in hippocampal slices of wild-type mice and GluR epsilon 1 (NR2A) subunit knockout mice. Electrical stimulations at the CA3 stratum radiatum or stratum oriens activate both commissural and associational (C/A).synapses, whereas stimulations at ventral fimbria mainly activate commissural synapses. Ro 25-6981 and ifenprodil, the GluR epsilon 2 (NR2B) subunit-selective NMDA receptor antagonists, suppressed NMDA receptor-mediated excitatory postsynaptic currents (NMDA EPSCs) at the commissural-CA3 synapses on basal dendrites more strongly than those at the C/A-CA3 synapses on apical or basal dendrites. However, glutamate-evoked NMDA receptor currents were reduced by the GluR epsilon 1 subunit knockout to a similar extent at both apical and basal dendrites. The GluR epsilon 1 subunit knockout also reduced NMDA EPSCs at the C/A-CA3 synapses on basal dendrites, but did not affect NMDA EPSCs at the commissural-CA3 synapses on basal dendrites. These results confirmed our previous findings that NMDA receptors operating at different synapses in CA3 pyramidal cells have different GluR epsilon subunit compositions, and further show that the GluR epsilon subunit composition may be regulated depending on the types of synaptic inputs, even within a single CA3 pyramidal neuron. (C) 2000 Elsevier Science Ltd. All rights reserved.