Neurexin1⍺ differentially regulates synaptic efficacy within striatal circuits.
Neurexin1⍺ differentially regulates synaptic efficacy within striatal circuits.
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Neurexin1⍺对纹状体环路内突触的效能有不同的调节作用。
DOI：
10.1016/j.celrep.2021.108773
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发表时间：
2021-02-23
期刊：
影响因子：
8.8
通讯作者：
Fuccillo MV
中科院分区：
文献类型：
--
作者：
Davatolhagh MF;Fuccillo MV
突触功能必需基因的突变，如突触前粘附分子Neurexin1α (Nrxn1α)，与神经精神病理生理密切相关。纹状体作为基底神经节的输入核，整合了多种控制认知和运动控制的兴奋性投射，其损伤可能是疾病的复发途径。在这里，我们通过光遗传学介导的背前额皮质（dPFC）传入信号募集和背内侧纹状体（DMS）棘投射神经元（SPNs）的丘脑束旁连接来测试Nrxn1α在纹状体回路中的功能相关性。对于dPFC-DMS回路，我们发现Nrxn1α+/ -和Nrxn1α - / -小鼠的间接通路spn上的突触强度下降，这是由神经递质释放减少引起的。相比之下，尽管突触n -甲基- d -天冬氨酸受体（NMDAR）含量发生变化，但丘脑对DMS的兴奋性输入表现出相对正常的兴奋性突触强度。这些发现表明Nrxn1α的失调以输入特异性和靶标特异性的方式调节纹状体功能。Davatolhagh和Fuccillo证明，突触细胞粘附分子Nrxn1α的缺失导致背侧内侧纹状体中来自背侧前额叶皮层和丘脑束旁核输入的突触表型不同。这些发现表明纹状体回路活动的输入特异性失衡是神经发育障碍模型中的一个关键扰动。
Mutations in genes essential for synaptic function, such as the presynaptic adhesion molecule Neurexin1α (Nrxn1α), are strongly implicated in neuropsychiatric pathophysiology. As the input nucleus of the basal ganglia, the striatum integrates diverse excitatory projections governing cognitive and motor control, and its impairment may represent a recurrent pathway to disease. Here, we test the functional relevance of Nrxn1α in striatal circuits by employing optogenetic-mediated afferent recruitment of dorsal prefrontal cortical (dPFC) and parafascicular thalamic connections onto dorsomedial striatal (DMS) spiny projection neurons (SPNs). For dPFC-DMS circuits, we find decreased synaptic strength specifically onto indirect pathway SPNs in both Nrxn1α+/− and Nrxn1α−/− mice, driven by reductions in neurotransmitter release. In contrast, thalamic excitatory inputs to DMS exhibit relatively normal excitatory synaptic strength despite changes in synaptic N-methyl-D-aspartate receptor (NMDAR) content. These findings suggest that dysregulation of Nrxn1α modulates striatal function in an input- and target-specific manner. Davatolhagh and Fuccillo demonstrate that loss of Nrxn1α, a synaptic cell adhesion molecule, leads to divergent synaptic phenotypes within dorsal medial striatum for inputs from dorsal prefrontal cortex and parafascicular thalamic nucleus. These findings suggest input-specific imbalances in striatal circuit activity as a key perturbation in models of neurodevelopmental disorders.
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影响因子：
8.8
作者：
Benthall KN;Ong SL;Bateup HS
通讯作者：
Bateup HS
纹状体培养基神经元的功能连接组。
DOI：
10.1523/jneurosci.3833-10.2011
发表时间：
2011-01-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chuhma N;Tanaka KF;Hen R;Rayport S
通讯作者：
Rayport S
影响因子：
7.7
作者：
Alabi OO;Davatolhagh MF;Robinson M;Fortunato MP;Vargas Cifuentes L;Kable JW;Fuccillo MV
通讯作者：
Fuccillo MV
DOI：
10.1002/ajmg.b.31063
发表时间：
2010-06-05
影响因子：
2.8
作者：
Ching, Michael S. L.;Shen, Yiping;Tan, Wen-Hann;Jeste, Shafali S.;Morrow, Eric M.;Chen, Xiaoli;Mukaddes, Nahit M.;Yoo, Seung-Yun;Hanson, Ellen;Hundley, Rachel;Austin, Christina;Becker, Ronald E.;Berry, Gerard T.;Driscoll, Katherine;Engle, Elizabeth C.;Friedman, Sandra;Gusella, James F.;Hisama, Fuki M.;Irons, Mira B.;Lafiosca, Tina;LeClair, Elaine;Miller, David T.;Neessen, Michael;Picker, Jonathan D.;Rappaport, Leonard;Rooney, Cynthia M.;Sarco, Dean P.;Stoler, Joan M.;Walsh, Christopher A.;Wolff, Robert R.;Zhang, Ting;Nasir, Ramzi H.;Wu, Bai-Lin
通讯作者：
Wu, Bai-Lin
影响因子：
5.3
作者：
Corbit, Victoria L.;Manning, Elizabeth E.;Ahmari, Susanne E.
通讯作者：
Ahmari, Susanne E.