Ravi Namasivayam, Li Zhijun, Oettl Lars-Lennart, Bartsch Dusan, Schönig Kai, Kelsch Wolfgang
Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim 68159, Germany German Cancer Research Center, Heidelberg 69120, Germany.
German Cancer Research Center, Heidelberg 69120, Germany.
Development. 2015 Jan 15;142(2):303-13. doi: 10.1242/dev.110767. Epub 2014 Dec 17.
New granule cell neurons (GCs) generated in the neonatal and adult subventricular zone (SVZ) have distinct patterns of input synapses in their dendritic domains. These synaptic input patterns determine the computations that the neurons eventually perform in the olfactory bulb. We observed that GCs generated earlier in postnatal life had acquired an 'adult' synaptic development only in one dendritic domain, and only later-born GCs showed an 'adult' synaptic development in both dendritic domains. It is unknown to what extent the distinct synaptic input patterns are already determined in SVZ progenitors and/or by the brain circuit into which neurons integrate. To distinguish these possibilities, we heterochronically transplanted retrovirally labeled SVZ progenitor cells. Once these transplanted progenitors, which mainly expressed Mash1, had differentiated into GCs, their glutamatergic input synapses were visualized by genetic tags. We observed that GCs derived from neonatal progenitors differentiating in the adult maintained their characteristic neonatal synapse densities. Grafting of adult SVZ progenitors to the neonate had a different outcome. These GCs formed synaptic densities that corresponded to neither adult nor neonatal patterns in two dendritic domains. In summary, progenitors in the neonatal and adult brain generate distinct GC populations and switch their fate to generate neurons with specific synaptic input patterns. Once they switch, adult progenitors require specific properties of the circuit to maintain their characteristic synaptic input patterns. Such determination of synaptic input patterns already at the progenitor-cell level may be exploited for brain repair to engineer neurons with defined wiring patterns.
新生和成年脑室下区（SVZ）产生的新颗粒细胞神经元（GCs）在其树突域具有不同的输入突触模式。这些突触输入模式决定了神经元最终在嗅球中执行的计算。我们观察到，出生后早期产生的GCs仅在一个树突域获得了“成年”突触发育，而只有较晚出生的GCs在两个树突域都表现出“成年”突触发育。目前尚不清楚不同的突触输入模式在SVZ祖细胞中以及/或者由神经元整合进入的脑回路在多大程度上已经被确定。为了区分这些可能性，我们进行了异时性逆转录病毒标记的SVZ祖细胞移植。一旦这些主要表达Mash1的移植祖细胞分化为GCs，它们的谷氨酸能输入突触就通过基因标签可视化。我们观察到，在成年期分化的源自新生祖细胞的GCs保持了其特征性的新生突触密度。将成年SVZ祖细胞移植到新生动物中有不同的结果。这些GCs在两个树突域形成的突触密度既不符合成年模式也不符合新生模式。总之，新生和成年大脑中的祖细胞产生不同的GC群体，并改变其命运以产生具有特定突触输入模式的神经元。一旦它们发生改变，成年祖细胞需要回路的特定属性来维持其特征性的突触输入模式。这种在祖细胞水平就对突触输入模式进行的确定可能被用于脑修复，以构建具有特定布线模式的神经元。
