Anatomical and Functional Connectivity at the Dendrodendritic Reciprocal Mitral Cell-Granule Cell Synapse: Impact on Recurrent and Lateral Inhibition.
Anatomical and Functional Connectivity at the Dendrodendritic Reciprocal Mitral Cell-Granule Cell Synapse: Impact on Recurrent and Lateral Inhibition.
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DOI：
10.3389/fncir.2022.933201
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发表时间：
2022
影响因子：
3.5
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中科院分区：
文献类型：
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在脊椎动物嗅球中，其主要神经元、二尖瓣细胞和簇状细胞以及外丛状层的抑制性中间神经元之间的互反树突相互作用介导了周期性和侧向抑制，这些中间神经元中数量最多的是颗粒细胞。在这里，我们使用最近建立的解剖学参数和单一突触传递的功能数据，定量模拟了大鼠嗅球颗粒细胞的反向棘对二尖瓣细胞的反复抑制强度。我们的功能数据使我们得到0.2 nS量级的单一突触传导。模拟结果表明，近端单个颗粒细胞输入的体电压偏转低于检测阈值，且随距离的衰减大致呈线性，无源长度常数为650 μm。然而，由于二尖瓣细胞动作电位的反复抑制将源于数百个相互的棘，因此即使在许多输入之间存在大量的相互分流，累计的反复IPSP将会大得多。接下来，我们更新并完善了整个大鼠嗅球内预先存在的连接模型，首先是二尖瓣细胞和颗粒细胞之间的连接模型，以估计依赖于细胞之间距离的复发性抑制的可能性和影响。此外，为了表征侧抑制的底物，我们估计了任何两个二尖瓣细胞或属于功能性肾小球集合的所有二尖瓣细胞（即从同一肾小球接受输入）之间通过颗粒细胞的连通性，再次作为二尖瓣细胞和/或整个肾小球二尖瓣细胞集合之间距离的函数。我们的研究结果预测了肾小球群之间解剖连通性的三种机制的程度：肾小球群内部和相邻肾小球的前四环的高连通性，多达11个肾小球的实质性连通性，以及可忽略的连通性。最后，在首次尝试估计颗粒细胞介导的侧抑制的功能强度时，我们将这一解剖学估计与上述随距离衰减的模拟结果结合起来，与解剖学连通性相比，导致功能影响的范围略有缩小。
In the vertebrate olfactory bulb, reciprocal dendrodendritic interactions between its principal neurons, the mitral and tufted cells, and inhibitory interneurons in the external plexiform layer mediate both recurrent and lateral inhibition, with the most numerous of these interneurons being granule cells. Here, we used recently established anatomical parameters and functional data on unitary synaptic transmission to simulate the strength of recurrent inhibition of mitral cells specifically from the reciprocal spines of rat olfactory bulb granule cells in a quantitative manner. Our functional data allowed us to derive a unitary synaptic conductance on the order of 0.2 nS. The simulations predicted that somatic voltage deflections by even proximal individual granule cell inputs are below the detection threshold and that attenuation with distance is roughly linear, with a passive length constant of 650 μm. However, since recurrent inhibition in the wake of a mitral cell action potential will originate from hundreds of reciprocal spines, the summated recurrent IPSP will be much larger, even though there will be substantial mutual shunting across the many inputs. Next, we updated and refined a preexisting model of connectivity within the entire rat olfactory bulb, first between pairs of mitral and granule cells, to estimate the likelihood and impact of recurrent inhibition depending on the distance between cells. Moreover, to characterize the substrate of lateral inhibition, we estimated the connectivity via granule cells between any two mitral cells or all the mitral cells that belong to a functional glomerular ensemble (i.e., which receive their input from the same glomerulus), again as a function of the distance between mitral cells and/or entire glomerular mitral cell ensembles. Our results predict the extent of the three regimes of anatomical connectivity between glomerular ensembles: high connectivity within a glomerular ensemble and across the first four rings of adjacent glomeruli, substantial connectivity to up to eleven glomeruli away, and negligible connectivity beyond. Finally, in a first attempt to estimate the functional strength of granule-cell mediated lateral inhibition, we combined this anatomical estimate with our above simulation results on attenuation with distance, resulting in slightly narrowed regimes of a functional impact compared to the anatomical connectivity.
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