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

神经肽加压素(VP)是脊椎动物社会行为的主要媒介，最好的描述是在关键的边缘大脑区域，如下丘脑和杏仁核。然而，嗅球内固有的VP系统及其对社会气味处理的影响还相对较少。到目前为止，球部VP细胞被描述为谷氨酸能的外部簇状细胞，它用树突丛支配单个肾小球，VP被证明减少了主二尖瓣细胞的输出。这一行动很可能是针对个人的社会气味歧视所必需的。具体的生理机制，如VP如何准确地调节特定社会气味在细胞和球茎的系统水平上的编码，目前还远未被了解。此外，在细胞水平上的VP神经调节和这些机制如何实际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说，基于第一个初步数据，可以解释社会气味特定的信号是如何实现和存储的VP系统在细胞水平。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)细胞和亚细胞解剖学，(2)网络相互作用，(3)与行为的耦合。因此，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伙伴，重点是肾小球相互作用。虽然带有肾小球束的兴奋性球神经元通常由嗅神经输入兴奋，但我们发现转基因大鼠中的GFP+-VP细胞在嗅神经刺激时接受双相输入，具有早期、强大的GABA能成分，其确切来源有待进一步探索。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，以触发局部VP的释放。候选者是来自副嗅球和前嗅核的远程输入。众所周知，这些结构调节主嗅球中的气味信号，特别是在气味依赖的社会行为背景下。我们还计划利用急性脑片中的钙离子群体成像，监测内在VP系统对球部网络活动的影响。最后，我们计划测试之前建立的蜂窝候选机制在实际社会行为中的参与程度。简而言之，我们将通过具体操作延髓VP系统，包括不同的VP受体和GABAA受体亚型，从药理上调节幼年大鼠的社会辨别能力。我们预计，对延髓VP系统在气味引导的社会行为中操作的细胞基础的深入了解，也将有助于阐明VPerar能在一般社会认知过程中控制皮质和边缘脑结构的细胞机制。

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.