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CaV3.2基因敲除小鼠的视网膜电波发生改变,但方向选择性正常。

CaV3.2 KO mice have altered retinal waves but normal direction selectivity.

作者信息

Hamby Aaron M, Rosa Juliana M, Hsu Ching-Hsiu, Feller Marla B

机构信息

Department of Molecular and Cell Biology,University of California,Berkeley,Berkeley,California.

出版信息

Vis Neurosci. 2015 Jan;32:E003. doi: 10.1017/S0952523814000364.

Abstract

Early in development, before the onset of vision, the retina establishes direction-selective responses. During this time period, the retina spontaneously generates bursts of action potentials that propagate across its extent. The precise spatial and temporal properties of these "retinal waves" have been implicated in the formation of retinal projections to the brain. However, their role in the development of direction selective circuits within the retina has not yet been determined. We addressed this issue by combining multielectrode array and cell-attached recordings to examine mice that lack the CaV3.2 subunit of T-type Ca2+ channels (CaV3.2 KO) because these mice exhibit disrupted waves during the period that direction selective circuits are established. We found that the spontaneous activity of these mice displays wave-associated bursts of action potentials that are altered from that of control mice: the frequency of these bursts is significantly decreased and the firing rate within each burst is reduced. Moreover, the projection patterns of the retina demonstrate decreased eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN). However, after eye-opening, the direction selective responses of CaV3.2 KO direction selective ganglion cells (DSGCs) are indistinguishable from those of wild-type DSGCs. Our data indicate that although the temporal properties of the action potential bursts associated with retinal waves are important for activity-dependent refining of retinal projections to central targets, they are not critical for establishing direction selectivity in the retina.

摘要

在发育早期,在视觉出现之前,视网膜就建立了方向选择性反应。在此期间,视网膜会自发产生跨其范围传播的动作电位爆发。这些“视网膜波”精确的时空特性与视网膜向大脑投射的形成有关。然而,它们在视网膜内方向选择性回路发育中的作用尚未确定。我们通过结合多电极阵列和细胞贴附记录来研究缺乏T型Ca2+通道CaV3.2亚基的小鼠(CaV3.2基因敲除小鼠,CaV3.2 KO)来解决这个问题,因为这些小鼠在方向选择性回路建立期间表现出视网膜波紊乱。我们发现,这些小鼠的自发活动表现出与动作电位爆发相关的波,这些波与对照小鼠的不同:这些爆发的频率显著降低,并且每次爆发内的放电率也降低。此外,视网膜的投射模式显示在背侧外侧膝状核(dLGN)中眼特异性分离减少。然而,在睁眼后,CaV3.2基因敲除方向选择性神经节细胞(DSGCs)的方向选择性反应与野生型DSGCs的反应无法区分。我们的数据表明,虽然与视网膜波相关的动作电位爆发的时间特性对于视网膜向中枢靶点的活动依赖性精细化很重要,但它们对于在视网膜中建立方向选择性并不关键。

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