Evidence for functionally distinct synaptic NMDA receptors in ventromedial versus dorsolateral striatum

Evidence for functionally distinct synaptic NMDA receptors in ventromedial versus dorsolateral striatum
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DOI:
10.1152/jn.00342.2002
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发表时间:
2003-01-01
影响因子:
2.5
通讯作者:
Wilcox, KS
Wilcox, KS
中科院分区:
医学3区
文献类型:
--
作者:
Chapman, DE;Keefe, KA;Wilcox, KS

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n -甲基- d -天冬氨酸受体(NMDARs)由不同的亚基组成。NR2亚基赋予NMDARs不同的药理学和生物物理特性。尽管NR2B亚基在纹状体中的表达是一致的,但NR2A亚基在纹状体的横向表达更大。采用最小局部刺激诱导药理学分离的nmdar介导的兴奋性突触后电流(NMDAR-EPSCs),并记录在整个细胞结构中,以验证纹状体神经元NMDAR-EPSCs的生物物理和药理学特性会随其在成年大鼠纹状体中的位置而变化的假设。我们观察到NMDAR-EPSCs在腹内侧纹状体神经元中的衰减时间动力学明显慢于背外侧纹状体。尽管伊芬普罗地尔对这些区域的NMDAR-EPSCs没有差异影响,但甘氨酸或d -丝氨酸选择性地增加了背外侧纹状体中NMDAR-EPSCs的峰值电流。这些数据为在成年啮齿动物大脑同一区域的同一神经元类型中存在功能不同的NMDARs提供了证据。因此,这些数据表明,在成年啮齿动物大脑的腹内侧纹状体和背外侧纹状体中,兴奋性输入的突触加工的性质是不同的,这两个区域分别参与边缘和感觉运动过程。
N-methyl-D-aspartate receptors (NMDARs) are comprised of different subunits. NR2 subunits confer different pharmacological and biophysical properties to NMDARs. Although NR2B subunit expression is uniform throughout striatum, NR2A subunit expression is greater laterally. Pharmacologically isolated NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs) were elicited using minimal local stimulation and recorded in the whole cell configuration to test the hypothesis that biophysical and pharmacological properties of NMDAR-EPSCs of striatal neurons would vary as a function of their location in adult rat striatum. We observed that the decay-time kinetics of NMDAR-EPSCs are significantly slower in neurons of ventromedial versus dorsolateral striatum. Whereas ifenprodil did not differentially affect NMDAR-EPSCs in these regions, application of either glycine or D-serine increased the peak current of NMDAR-EPSCs selectively in dorsolateral striatum. These data provide evidence for functionally distinct NMDARs in the same neuron type in the same brain region of the adult rodent brain. These data thus suggest that the nature of synaptic processing of excitatory input is different in the ventromedial and dorsolateral striatum of the adult rodent brain, regions differentially involved in limbic versus sensorimotor processes, respectively.