Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, SE1 1UL, United Kingdom
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, United Kingdom.
J Neurosci. 2021 Mar 10;41(10):2135-2151. doi: 10.1523/JNEUROSCI.1606-20.2020. Epub 2021 Jan 22.
Can alterations in experience trigger different plastic modifications in neuronal structure and function, and if so, how do they integrate at the cellular level? To address this question, we interrogated circuitry in the mouse olfactory bulb responsible for the earliest steps in odor processing. We induced experience-dependent plasticity in mice of either sex by blocking one nostril for one day, a minimally invasive manipulation that leaves the sensory organ undamaged and is akin to the natural transient blockage suffered during common mild rhinal infections. We found that such brief sensory deprivation produced structural and functional plasticity in one highly specialized bulbar cell type: axon-bearing dopaminergic neurons in the glomerular layer. After 24 h naris occlusion, the axon initial segment (AIS) in bulbar dopaminergic neurons became significantly shorter, a structural modification that was also associated with a decrease in intrinsic excitability. These effects were specific to the AIS-positive dopaminergic subpopulation because no experience-dependent alterations in intrinsic excitability were observed in AIS-negative dopaminergic cells. Moreover, 24 h naris occlusion produced no structural changes at the AIS of bulbar excitatory neurons, mitral/tufted and external tufted cells, nor did it alter their intrinsic excitability. By targeting excitability in one specialized dopaminergic subpopulation, experience-dependent plasticity in early olfactory networks might act to fine-tune sensory processing in the face of continually fluctuating inputs. Sensory networks need to be plastic so they can adapt to changes in incoming stimuli. To see how cells in mouse olfactory circuits can change in response to sensory challenges, we blocked a nostril for just one day, a naturally relevant manipulation akin to the deprivation that occurs with a mild cold. We found that this brief deprivation induces forms of axonal and intrinsic functional plasticity in one specific olfactory bulb cell subtype: axon-bearing dopaminergic interneurons. In contrast, intrinsic properties of axon-lacking bulbar dopaminergic neurons and neighboring excitatory neurons remained unchanged. Within the same sensory circuits, specific cell types can therefore make distinct plastic changes in response to an ever-changing external landscape.
体验的改变能否引发神经元结构和功能的不同可塑性改变？如果可以，它们在细胞水平上是如何整合的？为了解决这个问题，我们研究了负责气味处理最初步骤的小鼠嗅球中的回路。我们通过阻塞一只鼻孔一天来诱导雌雄小鼠的经验依赖性可塑性，这是一种微创操作，不会损坏感觉器官，类似于在常见的轻度鼻感染期间自然短暂阻塞所经历的情况。我们发现，这种短暂的感觉剥夺会导致一种高度特化的球型细胞类型产生结构和功能可塑性：在肾小球层中带有轴突的多巴胺能神经元。在鼻阻塞 24 小时后，球型多巴胺能神经元的轴突起始段（AIS）明显变短，这种结构改变与内在兴奋性降低有关。这些影响是 AIS 阳性多巴胺能亚群特有的，因为在 AIS 阴性多巴胺能细胞中没有观察到与经验相关的内在兴奋性改变。此外，鼻阻塞 24 小时不会引起球型兴奋性神经元（僧帽细胞/丛细胞和外丛细胞）AIS 上的结构变化，也不会改变它们的内在兴奋性。通过靶向一个特化的多巴胺能亚群的兴奋性，早期嗅觉网络中的经验依赖性可塑性可能会微调面对不断波动的输入时的感觉处理。感觉网络需要具有可塑性，以便它们能够适应传入刺激的变化。为了了解小鼠嗅觉回路中的细胞如何响应感觉挑战而发生变化，我们仅阻塞一个鼻孔一天，这是一种自然相关的操作，类似于轻度感冒时发生的剥夺。我们发现，这种短暂的剥夺会在一种特定的嗅球细胞亚型中诱导出轴突和内在功能可塑性：带有轴突的多巴胺能中间神经元。相比之下，缺乏轴突的球型多巴胺能神经元和相邻的兴奋性神经元的内在特性保持不变。在相同的感觉回路中，因此，特定的细胞类型可以对不断变化的外部环境做出不同的可塑性改变。
