Li Xiaoting, Hémond Gabriel, Godin Antoine G, Doyon Nicolas
Department of Mathematics and Statistics, Université Laval, Québec City, QC, Canada.
Department of Psychiatry and Neuroscience, Université Laval, Québec City, QC, Canada.
Front Comput Neurosci. 2022 Sep 28;16:969119. doi: 10.3389/fncom.2022.969119. eCollection 2022.
Understanding synaptic transmission is of crucial importance in neuroscience. The spatial organization of receptors, vesicle release properties and neurotransmitter molecule diffusion can strongly influence features of synaptic currents. Newly discovered structures coined trans-synaptic nanocolumns were shown to align presynaptic vesicles release sites and postsynaptic receptors. However, how these structures, spanning a few tens of nanometers, shape synaptic signaling remains little understood. Given the difficulty to probe submicroscopic structures experimentally, computer modeling is a useful approach to investigate the possible functional impacts and role of nanocolumns. In our model, as has been experimentally observed, a nanocolumn is characterized by a tight distribution of postsynaptic receptors aligned with the presynaptic vesicle release site and by the presence of trans-synaptic molecules which can modulate neurotransmitter molecule diffusion. In this work, we found that nanocolumns can play an important role in reinforcing synaptic current mostly when the presynaptic vesicle contains a small number of neurotransmitter molecules. Our work proposes a new methodology to investigate how the existence of trans-synaptic nanocolumns, the nanometric organization of the synapse and the lateral diffusion of receptors shape the features of the synaptic current such as its amplitude and kinetics.
理解突触传递在神经科学中至关重要。受体的空间组织、囊泡释放特性和神经递质分子扩散会强烈影响突触电流的特征。新发现的被称为跨突触纳米柱的结构显示可使突触前囊泡释放位点和突触后受体对齐。然而,这些跨度几十纳米的结构如何塑造突触信号仍知之甚少。鉴于通过实验探测亚微观结构存在困难,计算机建模是研究纳米柱可能的功能影响和作用的有用方法。在我们的模型中,正如实验观察到的那样,纳米柱的特征是突触后受体紧密分布并与突触前囊泡释放位点对齐,以及存在可调节神经递质分子扩散的跨突触分子。在这项工作中,我们发现纳米柱主要在突触前囊泡包含少量神经递质分子时,可在增强突触电流方面发挥重要作用。我们的工作提出了一种新方法,用于研究跨突触纳米柱的存在、突触的纳米级组织以及受体的横向扩散如何塑造突触电流的特征,如电流幅度和动力学。