Stincic Todd L, Keeley Patrick W, Reese Benjamin E, Taylor W Rowland
Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University , Portland, Oregon.
Neuroscience Research Institute, University of California , Santa Barbara, California.
J Neurophysiol. 2018 Oct 1;120(4):2121-2129. doi: 10.1152/jn.00322.2018. Epub 2018 Aug 8.
Cell-intrinsic factors, in conjunction with environmental signals, guide migration, differentiation, and connectivity during early development of neuronal circuits. Within the retina, inhibitory starburst amacrine cells (SBACs) comprise ON types with somas in the ganglion cell layer (GCL) and dendrites stratifying narrowly in the inner half of the inner plexiform layer (IPL) and OFF types with somas in the inner nuclear layer (INL) and dendrites stratifying narrowly in the outer half of the IPL. The transcription factor Sox2 is crucial to this subtype specification. Without Sox2, many ON-type SBACs destined for the GCL settle in the INL while many that reach the GCL develop bistratified dendritic arbors. This study asked whether ON-type SBACs in Sox2-conditional knockout retinas exhibit selective connectivity only with ON-type bipolar cells or their bistratified morphology allows them to connect to both ON and OFF bipolar cells. Physiological data demonstrate that these cells receive ON and OFF excitatory inputs, indicating that the ectopically stratified dendrites make functional synapses with bipolar cells. The excitatory inputs were smaller and more transient in Sox2-conditional knockout compared with wild type; however, inhibitory inputs appeared largely unchanged. Thus dendritic stratification, rather than cellular identification, may be the major factor that determines ON vs. OFF connectivity. NEW & NOTEWORTHY Conditional knockout of the transcription factor Sox2 during early embryogenesis converts a monostratifying starburst amacrine cell into a bistratifying starburst cell. Here we show that these bistratifying starburst amacrine cells form functional synaptic connections with both ON and OFF bipolar cells. This suggests that normal ON vs. OFF starburst connectivity may not require distinct molecular specification. Proximity alone may be sufficient to allow formation of functional synapses.
细胞内在因子与环境信号共同作用,在神经回路早期发育过程中引导细胞迁移、分化和连接。在视网膜中,抑制性星爆无长突细胞(SBACs)包括位于神经节细胞层(GCL)的ON型细胞,其树突在内网状层(IPL)内侧狭窄分层;以及位于内核层(INL)的OFF型细胞,其树突在IPL外侧狭窄分层。转录因子Sox2对这种亚型特异性至关重要。没有Sox2时,许多注定要进入GCL的ON型SBACs会在内核层定居,而许多到达GCL的细胞会发育出双分层树突分支。本研究探讨了Sox2条件性敲除视网膜中的ON型SBACs是否仅与ON型双极细胞表现出选择性连接,或者它们的双分层形态是否使它们能够与ON型和OFF型双极细胞都建立连接。生理学数据表明,这些细胞接受ON型和OFF型兴奋性输入,这表明异位分层的树突与双极细胞形成了功能性突触。与野生型相比,Sox2条件性敲除中的兴奋性输入更小且更短暂;然而,抑制性输入在很大程度上似乎没有变化。因此,树突分层而非细胞识别可能是决定ON型与OFF型连接的主要因素。新发现与值得注意的点在胚胎早期发育过程中对转录因子Sox2进行条件性敲除,可将单分层的星爆无长突细胞转化为双分层的星爆细胞。在这里,我们表明这些双分层的星爆无长突细胞与ON型和OFF型双极细胞都形成了功能性突触连接。这表明正常的ON型与OFF型星爆连接可能不需要独特的分子特异性。仅靠接近程度可能就足以形成功能性突触。