Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, D-80336 Munich, Germany.
Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):E1152-61. doi: 10.1073/pnas.1218991110. Epub 2013 Mar 4.
Identifying the connectome of adult-generated neurons is essential for understanding how the preexisting circuitry is refined by neurogenesis. Changes in the pattern of connectivity are likely to control the differentiation process of newly generated neurons and exert an important influence on their unique capacity to contribute to information processing. Using a monosynaptic rabies virus-based tracing technique, we studied the evolving presynaptic connectivity of adult-generated neurons in the dentate gyrus (DG) of the hippocampus and olfactory bulb (OB) during the first weeks of their life. In both neurogenic zones, adult-generated neurons first receive local connections from multiple types of GABAergic interneurons before long-range projections become established, such as those originating from cortical areas. Interestingly, despite fundamental similarities in the overall pattern of evolution of presynaptic connectivity, there were notable differences with regard to the development of cortical projections: although DG granule neuron input originating from the entorhinal cortex could be traced starting only from 3 to 5 wk on, newly generated neurons in the OB received input from the anterior olfactory nucleus and piriform cortex already by the second week. This early glutamatergic input onto newly generated interneurons in the OB was matched in time by the equally early innervations of DG granule neurons by glutamatergic mossy cells. The development of connectivity revealed by our study may suggest common principles for incorporating newly generated neurons into a preexisting circuit.
鉴定成年产生神经元的连接组对于理解预先存在的电路如何通过神经发生得到改善是至关重要的。连接模式的变化可能控制新产生的神经元的分化过程，并对其独特的参与信息处理的能力产生重要影响。使用基于单突触狂犬病毒的示踪技术，我们研究了海马齿状回（DG）和嗅球（OB）中成年产生神经元的进化前突触连接，在它们生命的头几周内。在这两个神经发生区，成年产生的神经元首先从多种类型的 GABA 能中间神经元接收局部连接，然后才建立长程投射，如来自皮质区的投射。有趣的是，尽管前突触连接进化的总体模式存在基本相似之处，但在皮质投射的发育方面存在显著差异：尽管 DG 颗粒神经元起源于内嗅皮层的输入只能从第 3 周到第 5 周开始追踪，但 OB 中新生的神经元在第 2 周就已经接收到来自前嗅核和梨状皮质的输入。这种早期的谷氨酸能传入到 OB 中的新生中间神经元与 DG 颗粒神经元被谷氨酸能苔藓细胞同样早期支配的时间相匹配。我们的研究揭示的连接发育可能表明了将新产生的神经元纳入预先存在的电路的共同原则。
