Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells.
Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells.
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DOI：
10.1038/s41467-017-00218-y
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发表时间：
2017-07-28
影响因子：
16.6
通讯作者：
McBain CJ
中科院分区：
文献类型：
--
作者：
Chittajallu R;Wester JC;Craig MT;Barksdale E;Yuan XQ;Akgül G;Fang C;Collins D;Hunt S;Pelkey KA;McBain CJ
GABA 能中间神经元适当整合到新生皮质回路中对于确保大脑内正常的信息处理至关重要。与神经系统疾病相关的网络和认知缺陷，例如由 NMDA 受体功能减退引起的精神分裂症，主要归因于表达小白蛋白的中间神经元的功能障碍，这些中间神经元反常地表达低水平的突触 NMDA 受体。在这里，我们揭示了在整个出生后发育过程中，丘脑和内嗅皮层对海马神经胶质细胞的输入以大量 NMDA 受体介导的成分为特征。这种 NMDA 受体信号是发育程序的先决条件，最终负责适当的长程 AMPAR 介导的神经胶质细胞的募集。相比之下，神经胶质细胞上局部 Schaffer 侧突触的 AMPAR 介导的输入在 NMDA 受体消融后保持正常。这些传入特异性缺陷可能会影响海马内神经胶质细胞介导的抑制，我们的研究结果揭示了在以 NMDA 受体功能减退为特征的神经发育障碍的病因学中涉及这种相对未充分研究的中间神经元亚型的电路位点。正常的大脑功能取决于兴奋性和抑制性神经元正确组装成神经回路。作者在此表明，在小鼠产后早期发育过程中，神经胶质细胞适当整合到海马回路中需要通过长程突触输入活动向神经胶质细胞发出 NMDAR 信号。
Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction. Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.
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影响因子：
25
作者：
De Marco García NV;Priya R;Tuncdemir SN;Fishell G;Karayannis T
通讯作者：
Karayannis T
影响因子：
16.2
作者：
Gray JA;Shi Y;Usui H;During MJ;Sakimura K;Nicoll RA
通讯作者：
Nicoll RA
影响因子：
64.8
作者：
COBB, SR;BUHL, EH;SOMOGYI, P
通讯作者：
SOMOGYI, P
影响因子：
7.7
作者：
Bezaire, Marianne J.;Raikov, Ivan;Soltesz, Ivan
通讯作者：
Soltesz, Ivan
影响因子：
25
作者：
Chittajallu, Ramesh;Craig, Michael T.;McFarland, Ashley;Yuan, Xiaoqing;Geffen, Scott;Tricoire, Ludovic;Erkkila, Brian;Barron, Sean C.;Lopez, Carla M.;Liang, Barry J.;Jeffries, Brian W.;Pelkey, Kenneth A.;McBain, Chris J.
通讯作者：
McBain, Chris J.