Dopamine Triggers the Maturation of Striatal Spiny Projection Neuron Excitability during a Critical Period.
Dopamine Triggers the Maturation of Striatal Spiny Projection Neuron Excitability during a Critical Period.
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DOI：
10.1016/j.neuron.2018.06.044
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发表时间：
2018-08-08
期刊：
影响因子：
16.2
通讯作者：
Sulzer D
中科院分区：
文献类型：
--
作者：
Lieberman OJ;McGuirt AF;Mosharov EV;Pigulevskiy I;Hobson BD;Choi S;Frier MD;Santini E;Borgkvist A;Sulzer D
神经回路是在童年时期形成和完善的，包括通过神经元兴奋性的关键变化。在这里，我们研究了纹状体内在兴奋性的个体发育。我们发现，在小鼠出生后第一周到第三周，多巴胺神经传递增加，在第四周，棘突投射神经元(SPN)的内在兴奋性降低。在发育缺乏纹状体多巴胺的小鼠中，直接通路D1-SPN在P18之后未能经历兴奋性的成熟，并在成年后保持高度兴奋性。我们发现，D1-SPN不成熟是由于磷脂酰肌醇4，5-二磷酸动力学改变，从而导致Kir2电流缺乏正常的个体发育增加。多巴胺替代在出生时或在青少年发育的特定时期(P18-P28)纠正了SPN兴奋性的这些缺陷，但不是在成年期间。这些结果确定了多巴胺依赖的纹状体成熟的敏感期，这对神经发育障碍的病理生理学和治疗具有重要意义。利伯曼等人。证明纹状体多巴胺释放的个体发育增加是通过控制Kir2钾电流的直接通路棘突投射神经元兴奋性在出生后的发育所必需的。
Neural circuits are formed and refined during childhood, including via critical changes in neuronal excitability. Here, we investigated the ontogeny of striatal intrinsic excitability. We found that dopamine neuro-transmission increases from the first to the third postnatal week in mice and precedes the reduction in spiny projection neuron (SPN) intrinsic excitability during the fourth postnatal week. In mice developmentally deficient for striatal dopamine, direct pathway D1-SPNs failed to undergo maturation of excitability past P18 and maintained hyperexcitability into adulthood. We found that the absence of D1-SPN maturation was due to altered phosphatidylinositol 4,5-biphosphate dynamics and a consequent lack of normal ontogenetic increases in Kir2 currents. Dopamine replacement corrected these deficits in SPN excitability when provided from birth or during a specific period of juvenile development (P18–P28), but not during adulthood. These results identify a sensitive period of dopamine-dependent striatal maturation, with implications for the pathophysiology and treatment of neurodevelopmental disorders. Lieberman et al. demonstrate that ontogenetic increases in striatal dopamine release are required for the postnatal development of direct pathway spiny projection neuron excitability via control of Kir2 potassium currents.
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影响因子：
9.9
作者：
Feigin, A;Fukuda, M;Eidelberg, D
通讯作者：
Eidelberg, D
DOI：
10.1073/pnas.1006511108
发表时间：
2011-01-11
影响因子：
11.1
作者：
Ding, Yunmin;Won, Lisa;Kang, Un Jung
通讯作者：
Kang, Un Jung
影响因子：
7.6
作者：
Cao, Junran;Lotfipour, Shahrdad;Leslie, Frances M.
通讯作者：
Leslie, Frances M.
DOI：
10.1016/0165-3806(96)00004-1
发表时间：
1996-04-30
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Coulter, CL;Happe, HK;Murrin, LC
通讯作者：
Murrin, LC
影响因子：
2.7
作者：
Andersen, SL
通讯作者：
Andersen, SL