Ryglewski Stefanie, Vonhoff Fernando, Scheckel Kathryn, Duch Carsten
Institute of Neurobiology, Johannes Gutenberg University Mainz, 55099 Mainz, Germany.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Neuron. 2017 Feb 8;93(3):632-645.e6. doi: 10.1016/j.neuron.2016.12.043. Epub 2017 Jan 26.
Brain development requires correct targeting of multiple thousand synaptic terminals onto staggeringly complex dendritic arbors. The mechanisms by which input synapse numbers are matched to dendrite size, and by which synaptic inputs from different transmitter systems are correctly partitioned onto a postsynaptic arbor, are incompletely understood. By combining quantitative neuroanatomy with targeted genetic manipulation of synaptic input to an identified Drosophila neuron, we show that synaptic inputs of two different transmitter classes locally direct dendrite growth in a competitive manner. During development, the relative amounts of GABAergic and cholinergic synaptic drive shift dendrites between different input domains of one postsynaptic neuron without affecting total arbor size. Therefore, synaptic input locally directs dendrite growth, but intra-neuronal dendrite redistributions limit morphological variability, a phenomenon also described for cortical neurons. Mechanistically, this requires local dendritic Ca influx through Dα7nAChRs or through LVA channels following GABAR-mediated depolarizations. VIDEO ABSTRACT.
大脑发育需要将数千个突触终端准确地靶向到极其复杂的树突分支上。目前对于输入突触数量如何与树突大小相匹配，以及来自不同递质系统的突触输入如何正确地分配到一个突触后分支上的机制，我们还不完全清楚。通过将定量神经解剖学与对已鉴定的果蝇神经元的突触输入进行靶向基因操作相结合，我们发现两种不同递质类别的突触输入以竞争方式局部引导树突生长。在发育过程中，GABA能和胆碱能突触驱动的相对量会使一个突触后神经元的不同输入域之间的树突发生移位，而不影响总分支大小。因此，突触输入局部引导树突生长，但神经元内的树突重新分布限制了形态变异性，这种现象在皮质神经元中也有描述。从机制上讲，这需要通过Dα7nAChRs或在GABAR介导的去极化后通过LVA通道使树突局部Ca内流。视频摘要。
