The vassopressinergic system in the olfactory bulb: Neuronal mechanisms of social odor discrimination

嗅球中的血管加压系统：社会气味辨别的神经机制

• 批准号: 336677558
• 负责人: Professorin Dr. Veronica Egger
• 金额: --
• 依托单位: Institut für Zoologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/336677558?language=en
• 关键词: vassopressinergic; system; olfactory; bulb; Neuronal

The neuropeptide vasopressin (VP) is a major mediator of vertebrate social behavior, best described within key limbic brain areas, like the hypothalamus and the amygdala. However, the intrinsic VP system in the olfactory bulb and therewith its influence on social odor processing are relatively unexplored. So far, bulbar VP cells are described as glutamatergic external tufted cells that innervate individual glomeruli with a dendritic tuft, and VP has been shown to reduce output from the principal mitral cells. This action is most likely required for individual social odor discrimination. The detailed physiological mechanisms, e.g. precisely how VP mediates the encoding of specifically social odors on the cellular and the systemic level of the bulb, are far from being understood. Further, there exists a conceptual gap between VP neuromodulation on the cellular level and how these mechanisms actually account for the maintenance of social memory. Here we present a detailed working hypothesis based on first preliminary data that could explain how social-odor-specific signaling is implemented and stored by the VP system at the cellular level. To test this concept the bulbar VP system needs to be characterized in several respects, i.e. (1) cellular and subcellular anatomy, (2) network interactions, and (3) coupling to behavior.Thus, we first plan to identify synaptic partners of VP cell dendrites and axons at the histological and ultrastructural level, with a focus on glomerular interactions. Although excitatory bulbar neurons with glomerular tufts are typically excited by olfactory nerve input, we have found that GFP+-VP cells in a transgenic rat line receive biphasic input upon olfactory nerve stimulation with an early, strong GABAergic component, whose precise origin needs to be further explored. According to our concept, the delayed, weaker excitatory inputs should coincide with additional excitatory social-specific inputs to trigger local release of VP. Candidates are long-range inputs from the accessory olfactory bulb and the anterior olfactory nucleus. These structures are known to modulate odor signaling in the main olfactory bulb, in particular in the context of odor-dependent social behaviors. We also plan to monitor the impact of the intrinsic VP system on bulbar network activity, using Ca2+ population imaging in acute slices. Finally, we plan to test the involvement of the previously established cellular candidate mechanisms in actual social behavior. Briefly, we will pharmacologically modulate the social discrimination abilities of juvenile rats by manipulating specifically the bulbar VP system, including distinct VP receptor and GABAA receptor subtypes.We expect that insights into the cellular underpinning of the operation of the bulbar VP system in odor-guided social behavior will also shed light onto the cellular mechanisms of VPergic control of cortical and limbic brain structures during social cognition in general.

神经肽血管加压素（VP）是脊椎动物社会行为的主要介质，在关键的边缘脑区域（如下丘脑和杏仁核）中得到了最好的描述。然而，在嗅球的内在VP系统及其对社会气味处理的影响是相对未知的。到目前为止，延髓VP细胞被描述为具有树突状簇的神经支配单个肾小球的神经元能外部簇状细胞，并且VP已被证明减少来自主二尖瓣细胞的输出。这种行为很可能是个人社会气味歧视所必需的。详细的生理机制，例如VP如何精确地介导特定的社会气味在细胞和系统水平的灯泡的编码，是远远没有被理解。此外，在细胞水平上的VP神经调节与这些机制实际上如何解释社会记忆的维持之间存在概念上的差距。在这里，我们提出了一个详细的工作假设的基础上，第一个初步的数据，可以解释如何社会气味特异性信号的实施和存储的VP系统在细胞水平上。为了验证这一概念，延髓VP系统需要在几个方面进行表征，即（1）细胞和亚细胞解剖，（2）网络相互作用，（3）耦合到behavior.Thus，我们首先计划在组织学和超微结构水平上确定VP细胞树突和轴突的突触伴侣，重点是肾小球相互作用。虽然具有肾小球簇的兴奋性延髓神经元通常由嗅觉神经输入兴奋，但我们发现转基因大鼠系中的GFP+-VP细胞在嗅觉神经刺激后接受双相输入，具有早期强GABA能成分，其确切来源需要进一步探索。根据我们的概念，延迟的，较弱的兴奋性输入应该与额外的兴奋性社会特异性输入相一致，以触发VP的局部释放。候选者是来自副嗅球和前嗅核的长程输入。已知这些结构调节主嗅球中的气味信号，特别是在气味依赖性社会行为的背景下。我们还计划在急性切片中使用Ca 2+群体成像来监测内在VP系统对延髓网络活动的影响。最后，我们计划测试先前建立的细胞候选机制在实际社会行为中的参与。简单地说，我们将通过特异性地操纵延髓VP系统来调节幼年大鼠的社会辨别能力，包括不同的VP受体和GABAA受体亚型。我们希望了解延髓VP系统在气味中的细胞基础，引导的社会行为也将阐明在社会认知过程中，VPergic控制皮质和边缘脑结构的细胞机制。将军