Extrasynaptic glutamate and inhibitory neurotransmission modulate ganglion cell participation during glutamatergic retinal waves
Extrasynaptic glutamate and inhibitory neurotransmission modulate ganglion cell participation during glutamatergic retinal waves
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DOI：
10.1152/jn.00039.2013
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发表时间：
2013-04-01
影响因子：
2.5
通讯作者：
Feller, Marla B.
中科院分区：
文献类型：
--
作者：
Firl, Alana;Sack, Georgeann S.;Feller, Marla B.
FIRL A，SACK GS，Newman ZL，Tani H，Feller MB。突触外谷氨酸和抑制性神经传递调节神经节细胞在谷氨酸能视网膜波中的参与。神经生理学杂志109：1969-1978,2013。2013年1月23日首次出版；DOI：10.1152/jn.00039.2013。-在小鼠出生后的头2周内，短暂的视网膜回路引起神经节细胞层(GCL)内去极化的自发启动和横向传播。谷氨酸能视网膜波出现在出生后第二周，此时GCL去极化是由离子型谷氨酸受体介导的。双极细胞是视网膜内谷氨酸的主要来源，这表明波的传播依赖于它们的激活。使用基于荧光共振能量转移的谷氨酸FLII81E-1MU光学传感器，我们发现视网膜波伴随着突触外谷氨酸在整个内网状层的大量瞬时增加。使用双光子钙成像记录大量细胞中的自发钙瞬变，我们发现，尽管这种空间弥散的去极化来源，但在视网膜波期间，只有GCL和内核层(INL)中的一部分神经元被强劲地去极化。应用谷氨酸转运体阻断剂dl-苏氨酸-β-苄氧天冬氨酸(25mM)可使两层神经元的参与显著增加，提示突触外谷氨酸浓度影响INL和GCL的细胞参与。相反，用GABAA受体拮抗剂加巴津和甘氨酸受体拮抗剂士的宁阻断抑制性传递增加了细胞对GCL的参与，而不显著影响INL。这些数据表明，在发育过程中，谷氨酸溢出提供了一个空间扩散的去极化来源，但抑制电路决定了GCL内的哪些神经元参与视网膜波。
Firl A, Sack GS, Newman ZL, Tani H, Feller MB. Extrasynaptic glutamate and inhibitory neurotransmission modulate ganglion cell participation during glutamatergic retinal waves. J Neurophysiol 109: 1969-1978, 2013. First published January 23, 2013; doi:10.1152/jn.00039.2013.-During the first 2 wk of mouse postnatal development, transient retinal circuits give rise to the spontaneous initiation and lateral propagation of depolarizations across the ganglion cell layer (GCL). Glutamatergic retinal waves occur during the second postnatal week, when GCL depolarizations are mediated by ionotropic glutamate receptors. Bipolar cells are the primary source of glutamate in the inner retina, indicating that the propagation of waves depends on their activation. Using the fluorescence resonance energy transfer-based optical sensor of glutamate FLII81E-1 mu, we found that retinal waves are accompanied by a large transient increase in extrasynaptic glutamate throughout the inner plexiform layer. Using two-photon Ca2+ imaging to record spontaneous Ca2+ transients in large populations of cells, we found that despite this spatially diffuse source of depolarization, only a subset of neurons in the GCL and inner nuclear layer (INL) are robustly depolarized during retinal waves. Application of the glutamate transporter blocker dl-threo-beta-benzyloxyaspartate (25 mu M) led to a significant increase in cell participation in both layers, indicating that the concentration of extrasynaptic glutamate affects cell participation in both the INL and GCL. In contrast, blocking inhibitory transmission with the GABA A receptor antagonist gabazine and the glycine receptor antagonist strychnine increased cell participation in the GCL without significantly affecting the INL. These data indicate that during development, glutamate spillover provides a spatially diffuse source of depolarization, but that inhibitory circuits dictate which neurons within the GCL participate in retinal waves.