Oscillatory Network Activity in the Accessory Olfactory Pathway: Mechanistic Basis and Functional Implications

辅助嗅觉通路中的振荡网络活动：机制基础和功能意义

• 批准号: 378028035
• 负责人: Professor Dr. Marc Spehr
• 金额: --
• 依托单位: Arbeitsgruppe Chemosensorik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/378028035?language=en
• 关键词: Oscillatory; Network; Activity; Accessory; Olfactory

For mammals, chemosensation is an essential sensory modality. Its importance is underscored by the existence of multiple chemosensory subsystems. Of these, the vomeronasal system (VNS) is specifically associated with social and other innate behaviors. The first brain region of the VNS is the accessory olfactory bulb (AOB). Although the AOB shares gross similarities with its main olfactory system counterpart, there are major differences between the structures. Thus, extrapolation of physiological principles from the main olfactory bulb to the AOB, downplays the unique features of AOB physiology. Some of the most prominent features of VNS signaling involve its temporal dimension. Specifically, stimulus exposure, sensory processing, and the time scales of downstream targets are all significantly slower compared to other sensory systems. In the main olfactory system, activity is tightly coupled to breathing, exerting strong impact on sensory processing. By contrast, vomeronasal neurons are isolated from the breathing cycle. Yet, the absence of direct respiration-linked inputs to the VNS does not mean that oscillatory activity is not important in this system. Indeed, this proposal is based on two recent discoveries from our own laboratories which indicate that oscillations are present, prominent, and likely an integral feature of VNS function. At present, the specific roles of time and oscillations in VNS function still remains unclear. In fact, we still lack a basic functional and phenomenological understanding of the temporal aspects of AOB processing. In particular, very little is known about how the unique biophysical properties of the principal neurons of this structure, AOB mitral cells (AMCs) impact their response profiles, how their local network interactions shape AOB information processing, and how spontaneous and evoked AMC activity affects sensory representations. The focus of the current proposal is the largely unexplored temporal signature of chemosensory signaling in the AOB, with an emphasis on the role of AMCs.Our study is organized into three aims, each of which involves both in vitro and in vivo approaches, and hence requires close collaboration between both our groups. First, we will analyze the cellular and network mechanisms underlying spontaneous formation of oscillating microcircuits in the idle state. Second, we will study how these oscillations are modulated by sensory stimulation and by top-down inputs. Third, we will investigate both the role of LFP patterns in AOB information processing and the mechanisms underlying them. In a broader context, our experiments are motivated not only by our shared interest in the functional impact of oscillations on information processing within the AOB, but also on their effects on target nuclei in the amygdala and hypothalamus. Although the latter are beyond the scope of the current proposal, they guide us as topics for our future studies.

对于哺乳动物来说，化学感觉是一种基本的感觉方式。多个化学感觉子系统的存在突显了它的重要性。其中，犁鼻系统(VNS)与社会和其他先天行为特别相关。VNS的第一个脑区是副嗅球(AOB)。虽然AOB与其主要的嗅觉系统有很大的相似之处，但在结构上有很大的不同。因此，从主嗅球到AOB的生理原理的推断，淡化了AOB生理学的独特特征。VNS信号的一些最显著的特征涉及其时间维度。具体地说，与其他感觉系统相比，刺激暴露、感觉处理和下游目标的时间尺度都要慢得多。在主嗅觉系统中，活动与呼吸紧密相连，对感觉处理产生强烈影响。相比之下，犁鼻神经元与呼吸周期是分离的。然而，没有直接与呼吸相关的输入到VNS并不意味着振荡活动在这个系统中不重要。事实上，这一建议是基于我们自己实验室的两项最新发现，这两项发现表明，振荡是存在的、显著的，而且可能是VNS功能的一个完整特征。目前，时间和振荡在VNS功能中的具体作用仍不清楚。事实上，我们仍然缺乏对AOB处理的时间方面的基本功能和现象学方面的理解。特别是，对于这种结构的主要神经元的独特生物物理性质如何影响它们的反应轮廓，它们的局部网络相互作用如何塑造AOB信息处理，以及自发和诱发的AMC活动如何影响感觉表征，人们知之甚少。目前的建议的重点是AOB中化学感觉信号的时间特征，重点是AMC的作用。我们的研究分为三个目标，每个目标都涉及体外和体内方法，因此需要我们两个小组之间的密切合作。首先，我们将分析在空闲状态下自发形成振荡微电路的细胞和网络机制。其次，我们将研究这些振荡是如何被感觉刺激和自上而下输入所调制的。第三，我们将研究LFP模式在AOB信息处理中的作用及其背后的机制。在更广泛的背景下，我们的实验不仅受到我们对AOB内振荡对信息处理的功能影响的共同兴趣的推动，也受到它们对杏仁核和下丘脑靶核的影响的影响。虽然后者超出了当前提案的范围，但它们作为我们未来研究的主题提供了指导。