Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States.
Elife. 2022 Nov 30;11:e82093. doi: 10.7554/eLife.82093.
The organization of neural circuits determines nervous system function. Variability can arise during neural circuit development (e.g. neurite morphology, axon/dendrite position). To ensure robust nervous system function, mechanisms must exist to accommodate variation in neurite positioning during circuit formation. Previously, we developed a model system in the ventral nerve cord to conditionally induce positional variability of a proprioceptive sensory axon terminal, and used this model to show that when we altered the presynaptic position of the sensory neuron, its major postsynaptic interneuron partner modified its dendritic arbor to match the presynaptic contact, resulting in functional synaptic input (Sales et al., 2019). Here, we investigate the cellular mechanisms by which the interneuron dendrites detect and match variation in presynaptic partner location and input strength. We manipulate the presynaptic sensory neuron by (a) ablation; (b) silencing or activation; or (c) altering its location in the neuropil. From these experiments we conclude that there are two opposing mechanisms used to establish functional connectivity in the face of presynaptic variability: presynaptic contact stimulates dendrite outgrowth locally, whereas presynaptic activity inhibits postsynaptic dendrite outgrowth globally. These mechanisms are only active during an early larval critical period for structural plasticity. Collectively, our data provide new insights into dendrite development, identifying mechanisms that allow dendrites to flexibly respond to developmental variability in presynaptic location and input strength.
神经回路的组织决定了神经系统的功能。在神经回路发育过程中（例如，神经突形态、轴突/树突位置）可能会出现变异性。为了确保神经系统功能的稳健性，必须存在机制来适应回路形成过程中神经突定位的变化。以前，我们在腹神经索中开发了一个模型系统，以条件诱导本体感受感觉轴突末梢的位置可变性，并使用该模型表明，当我们改变感觉神经元的突触前位置时，其主要的突触后中间神经元伙伴会改变其树突分支以匹配突触前接触，从而产生功能性突触输入（Sales 等人，2019 年）。在这里，我们研究了中间神经元树突检测和匹配突触前伙伴位置和输入强度变化的细胞机制。我们通过（a）消融；（b）沉默或激活；或（c）改变其在神经网中的位置来操纵突触前感觉神经元。从这些实验中，我们得出结论，有两种相反的机制用于在突触前变异性的情况下建立功能性连接：突触前接触刺激局部树突生长，而突触前活动抑制全局的突触后树突生长。这些机制仅在结构可塑性的早期幼虫关键期活跃。总的来说，我们的数据为树突发育提供了新的见解，确定了允许树突灵活响应突触前位置和输入强度发育变化的机制。
