Kirchner Jan H, Euler Lucas, Fritz Ingo, Ferreira Castro André, Gjorgjieva Julijana
School of Life Sciences, Technical University of Munich, Freising, Germany.
Computation in Neural Circuits Group, Max Planck Institute for Brain Research, Frankfurt, Germany.
Elife. 2025 Feb 3;12:RP87527. doi: 10.7554/eLife.87527.
Dendritic branching and synaptic organization shape single-neuron and network computations. How they emerge simultaneously during brain development as neurons become integrated into functional networks is still not mechanistically understood. Here, we propose a mechanistic model in which dendrite growth and the organization of synapses arise from the interaction of activity-independent cues from potential synaptic partners and local activity-dependent synaptic plasticity. Consistent with experiments, three phases of dendritic growth - overshoot, pruning, and stabilization - emerge naturally in the model. The model generates stellate-like dendritic morphologies that capture several morphological features of biological neurons under normal and perturbed learning rules, reflecting biological variability. Model-generated dendrites have approximately optimal wiring length consistent with experimental measurements. In addition to establishing dendritic morphologies, activity-dependent plasticity rules organize synapses into spatial clusters according to the correlated activity they experience. We demonstrate that a trade-off between activity-dependent and -independent factors influences dendritic growth and synaptic location throughout development, suggesting that early developmental variability can affect mature morphology and synaptic function. Therefore, a single mechanistic model can capture dendritic growth and account for the synaptic organization of correlated inputs during development. Our work suggests concrete mechanistic components underlying the emergence of dendritic morphologies and synaptic formation and removal in function and dysfunction, and provides experimentally testable predictions for the role of individual components.
树突分支和突触组织塑造了单个神经元和神经网络的计算。当神经元融入功能网络时，它们如何在大脑发育过程中同时出现，目前仍缺乏机制上的理解。在此，我们提出一个机制模型，其中树突生长和突触组织源于潜在突触伙伴的活动非依赖性线索与局部活动依赖性突触可塑性之间的相互作用。与实验一致，模型中自然出现了树突生长的三个阶段——过度生长、修剪和稳定。该模型生成了星状树突形态，在正常和受干扰的学习规则下捕捉了生物神经元的几个形态特征，反映了生物变异性。模型生成的树突具有与实验测量结果一致的近似最佳布线长度。除了建立树突形态外，活动依赖性可塑性规则还根据突触所经历的相关活动将突触组织成空间簇。我们证明，活动依赖性和非依赖性因素之间的权衡在整个发育过程中影响树突生长和突触位置，这表明早期发育变异性会影响成熟形态和突触功能。因此，一个单一的机制模型可以捕捉树突生长，并解释发育过程中相关输入的突触组织。我们的工作揭示了树突形态出现以及功能正常和功能失调时突触形成与消除背后的具体机制成分，并为各个成分的作用提供了可通过实验验证的预测。
