Neuroligin 1 modulates striatal glutamatergic neurotransmission in a pathway and NMDAR subunit-specific manner.
Neuroligin 1 modulates striatal glutamatergic neurotransmission in a pathway and NMDAR subunit-specific manner.
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DOI：
10.3389/fnsyn.2015.00011
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发表时间：
2015
影响因子：
3.7
通讯作者：
Powell CM
中科院分区：
文献类型：
--
作者：
Espinosa F;Xuan Z;Liu S;Powell CM
神经连接素1（Neuroligin 1，NL 1）与其突触前伴侣神经连接素1（Neurexin 1，Nxn 1）一起参与突触特化和突触维持。我们和其他人已经表明，NL 1也可以调节啮齿动物模型的中枢神经系统中的突触功能。这些分子/细胞变化可以转化为动物行为的改变，被认为类似于神经精神疾病的行为学。例如，在NL 1缺失小鼠的背侧纹状体中，我们先前报道了在中型棘神经元（MSNs）中N-甲基-D-天冬氨酸受体（NMDAR）介导的突触电流与α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）介导的突触电流的比率（NMDA/AMPA）降低。重要的是，这种NMDA/AMPA比率的降低与重复理毛的增加相关。纹状体是基底神经节（BG）的输入核。这种电路的经典模型意味着，有两个主要的途径，使不同的和有点相反的纹状体输出关键的功能，这些核团在调制运动行为。因此，我们开始更好地表征NL 1缺失对背侧纹状体的直接和间接途径的影响，通过遗传标记参与直接和间接途径的MSN。我们证明，NMDAR介导的电流的减少仅限于MSN的直接途径。此外，NMDAR介导的电流的减少主要是由于含有GluN 2A亚基的NMDAR的功能降低。相比之下，NL 1基因敲除（KO）小鼠中的间接途径MSN显示出在直接途径中未观察到的微型兴奋性神经传递频率的降低。因此，NL 1缺失差异影响背侧纹状体中的直接和间接通路MSN。这些发现对NL 1 KO小鼠的纹状体功能具有潜在的影响。
Together with its presynaptic partner Neurexin 1 (Nxn1), Neuroligin 1 (NL1) participates in synapse specification and synapse maintenance. We and others have shown that NL1 can also modulate glutamatergic synaptic function in the central nervous system of rodent models. These molecular/cellular changes can translate into altered animal behaviors that are thought to be analogous to symptomatology of neuropsychiatric disorders. For example, in dorsal striatum of NL1 deletion mice, we previously reported that the ratio N-methyl-D-aspartate receptor (NMDAR) mediated synaptic currents to α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) mediated synaptic currents (NMDA/AMPA) is reduced in medium spiny neuron (MSNs). Importantly, this reduction in NMDA/AMPA ratio correlated with increased repetitive grooming. The striatum is the input nucleus of the basal ganglia (BG). Classical models of this circuitry imply that there are two principal pathways that render distinct and somewhat opposite striatal outputs critical to the function of these nuclei in modulating motor behavior. Thus, we set out to better characterize the effects of NL1 deletion on direct and indirect pathways of the dorsal striatum by genetically labeling MSNs participating in the direct and indirect pathways. We demonstrate that a decrease in NMDAR-mediated currents is limited to MSNs of the direct pathway. Furthermore, the decrease in NMDAR-mediated currents is largely due to a reduction in function of NMDARs containing the GluN2A subunit. In contrast, indirect pathway MSNs in NL1 knockout (KO) mice showed a reduction in the frequency of miniature excitatory neurotransmission not observed in the direct pathway. Thus, NL1 deletion differentially affects direct and indirect pathway MSNs in dorsal striatum. These findings have potential implications for striatal function in NL1 KO mice.