Sorbonne Université et CNRS UMR 8256, Adaptation Biologique et Vieillissement, Paris, France.
Institut Pasteur, Université de Paris, CNRS UMR 3571, Unit of Synapse and Circuit Dynamics, Paris, France.
Elife. 2021 Nov 3;10:e65954. doi: 10.7554/eLife.65954.
Synaptic transmission, connectivity, and dendritic morphology mature in parallel during brain development and are often disrupted in neurodevelopmental disorders. Yet how these changes influence the neuronal computations necessary for normal brain function are not well understood. To identify cellular mechanisms underlying the maturation of synaptic integration in interneurons, we combined patch-clamp recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional reconstruction of SC morphology with excitatory synapse location, and biophysical modeling. We found that postnatal maturation of postsynaptic strength was homogeneously reduced along the somatodendritic axis, but dendritic integration was always sublinear. However, dendritic branching increased without changes in synapse density, leading to a substantial gain in distal inputs. Thus, changes in synapse distribution, rather than dendrite cable properties, are the dominant mechanism underlying the maturation of neuronal computation. These mechanisms favor the emergence of a spatially compartmentalized two-stage integration model promoting location-dependent integration within dendritic subunits.
在大脑发育过程中，突触传递、连接和树突形态同步成熟，并且在神经发育障碍中经常受到干扰。然而，这些变化如何影响正常大脑功能所需的神经元计算尚不清楚。为了确定中间神经元突触整合成熟的细胞机制，我们结合了对小鼠小脑星形细胞（SCs）兴奋性输入的膜片钳记录、SC 形态的三维重建以及兴奋性突触位置和生物物理建模。我们发现，突触后强度的出生后成熟沿体树突轴均匀降低，但树突整合始终呈亚线性。然而，树突分支增加而突触密度没有变化，导致远端输入大量增加。因此，突触分布的变化而不是树突电缆性质是神经元计算成熟的主要机制。这些机制有利于出现一种空间分区的两阶段整合模型，促进树突亚单位内位置依赖的整合。
