Arnson Hannah A, Strowbridge Ben W
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106.
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106
J Neurosci. 2017 Oct 25;37(43):10468-10480. doi: 10.1523/JNEUROSCI.1004-17.2017. Epub 2017 Sep 25.
Olfactory sensory input is detected by receptor neurons in the nose, which then send information to the olfactory bulb (OB), the first brain region for processing olfactory information. Within the OB, many local circuit interneurons, including axonless granule cells, function to facilitate fine odor discrimination. How interneurons interact with principal cells to affect bulbar processing is not known, but the mechanism is likely to be different from that in sensory cortical regions because the OB lacks an obvious topographical organization. Neighboring glomerular columns, representing inputs from different receptor neuron subtypes, typically have different odor tuning. Determining the spatial scale over which interneurons such as granule cells can affect principal cells is a critical step toward understanding how the OB operates. We addressed this question by assaying inhibitory synchrony using intracellular recordings from pairs of principal cells with different intersomatic spacing. We found, in acute rat OB slices from both sexes, that inhibitory synchrony is evident in the spontaneous synaptic input in mitral cells (MCs) separated up to 220 μm (300 μm with elevated K). At all intersomatic spacing assayed, inhibitory synchrony was dependent on Na channels, suggesting that action potentials in granule cells function to coordinate GABA release at relatively distant dendrodendritic synapses formed throughout the dendritic arbor. Our results suggest that individual granule cells are able to influence relatively large groups of MCs and tufted cells belonging to clusters of at least 15 glomerular modules, providing a potential mechanism to integrate signals reflecting a wide variety of odorants. Inhibitory circuits in the olfactory bulb (OB) play a major role in odor processing, especially during fine odor discrimination. However, how inhibitory networks enhance olfactory function, and over what spatial scale they operate, is not known. Interneurons are potentially able to function on both a highly localized, synapse-specific level and on a larger, spatial scale that encompasses many different glomerular channels. Although recent indirect evidence has suggested a relatively localized functional role for most inhibition in the OB, in the present study, we used paired intracellular recordings to demonstrate directly that inhibitory local circuits operate over large spatial scales by using fast action potentials to link GABA release at many different synaptic contacts formed with principal cells.
嗅觉感觉输入由鼻腔中的受体神经元检测到，这些神经元随后将信息发送到嗅球（OB），这是处理嗅觉信息的第一个脑区。在嗅球内，许多局部回路中间神经元，包括无轴突颗粒细胞，起到促进精细气味辨别的作用。中间神经元如何与主细胞相互作用以影响嗅球处理尚不清楚，但该机制可能与感觉皮层区域不同，因为嗅球缺乏明显的拓扑组织。代表来自不同受体神经元亚型输入的相邻肾小球柱通常具有不同的气味调谐。确定颗粒细胞等中间神经元能够影响主细胞的空间尺度是理解嗅球如何运作的关键一步。我们通过使用来自具有不同体细胞间距的主细胞对的细胞内记录来检测抑制性同步，从而解决了这个问题。我们发现，在来自两性的急性大鼠嗅球切片中，在相距达220μm（在高钾情况下为300μm）的二尖瓣细胞（MCs）的自发突触输入中，抑制性同步很明显。在所检测的所有体细胞间距下，抑制性同步都依赖于钠通道，这表明颗粒细胞中的动作电位起到协调在整个树突分支形成的相对远距离的树突-树突突触处的GABA释放的作用。我们的结果表明，单个颗粒细胞能够影响属于至少15个肾小球模块簇的相对大量的MCs和簇状细胞，提供了一种整合反映多种气味剂信号的潜在机制。嗅球（OB）中的抑制性回路在气味处理中起主要作用，尤其是在精细气味辨别过程中。然而，抑制性网络如何增强嗅觉功能以及它们在何种空间尺度上运作尚不清楚。中间神经元可能能够在高度局部化的、突触特异性水平以及涵盖许多不同肾小球通道的更大空间尺度上发挥作用。尽管最近的间接证据表明嗅球中大多数抑制作用具有相对局部化的功能作用，但在本研究中，我们使用配对细胞内记录直接证明，抑制性局部回路通过利用快速动作电位在与主细胞形成的许多不同突触接触处连接GABA释放，从而在大空间尺度上运作。
