Imaging olfactory network activity in a semi-intact nose-brain preparation: On the origin of spontaneous theta oscillations in the olfactory bulb

半完整鼻脑标本中嗅觉网络活动的成像：嗅球自发θ振荡的起源

• 批准号: 406690699
• 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: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/406690699?language=en
• 关键词: Imaging; olfactory; network; activity; semi

Oscillations of neuronal activity at the theta rhythm (4-8 Hz) occur in many vertebrate neuronal ensembles, most famously within circuits linked to hippocampal areas. In the olfactory system, theta oscillations are known to enable proper olfactory coding in rats and humans. Their origin has been tied to respiratory activity which can effect sensory input through the nose mainly by mechanosensitive, olfactory and trigeminal pathways. Our observation of respiration-independent theta oscillations in the olfactory bulb in an decerebrated semi-intact nose-brain preparation indicates that such oscillations can occur spontaneously, without any sensory or centrifugal inputs. Our main working hypothesis is that breathing and therewith respiratory patterning of bulbar activity tap an intrinsic resonance of the olfactory bulb network; the spontaneous theta oscillations observed in the bulb of the nose-brain preparation are a correlate of this resonance and can be entrained by respiratory-like sensory input. To investigate this idea, we plan to combine the nose-brain preparation with our expertise in two-photon imaging techniques to explore network function at the single neuron and ensemble level and thereby unravel the origin of spontaneous theta and its interaction with sensory input in an intact network. A strong candidate mechanism for the origin of spontaneous theta oscillations is intrinsic pacemaking in a juxtaglomerular cell type, the external tufted cell (ETC), since ETCs are known to produce spontaneous bursts of activity within the theta frequency range. Thus the first step in this project is to fully establish Ca2+ population imaging within the glomerular layer in the nose-brain preparation, based on a pre-existing resonant scanning two-photon microscope system. Because the ETCs are located close to the bulbar surface and their bursts are known to yield substantial Ca2+ influx, ETC somatic signals are an excellent target for Ca2+ imaging. Next we will investigate the spontaneous activity of ETCs in parallel with local field potential recordings and test their contribution to the theta rhythm by pharmacological means. Finally we will explore the coupling between sensory stimulation with odorants, respiratory-like airflow and ETC activity, as well as the parallel activity of the principal mitral and tufted cells. Such an approach will allow us to investigate physiological patterns of activity in the nose-brain preparation and thus study releavant network properties in an in vitro system.In summary, we aim to elucidate the mechanism of the intrinsic olfactory bulb theta rhythm and how it interacts with both sensory input and olfactory bulb output by the principal neurons. Our investigations might also contribute to the understanding of theta coding in other brain areas.

在许多脊椎动物神经元集合中，神经元活动以θ节律（4-8 Hz）振荡，最著名的是在与海马区相连的回路中。在嗅觉系统中，已知θ振荡使大鼠和人类能够进行适当的嗅觉编码。它们的起源与呼吸活动有关，呼吸活动主要通过机械敏感、嗅觉和三叉神经途径影响通过鼻子的感觉输入。我们在去大脑半完整的鼻脑标本中观察到嗅球中呼吸独立的θ振荡，表明这种振荡可以自发发生，而无需任何感觉或离心输入。我们的主要工作假设是，呼吸和呼吸模式的延髓活动挖掘的嗅球网络的固有共振;自发的θ振荡中观察到的灯泡的鼻-脑准备是一个相关的这种共振，并可以夹带由类似的感觉输入。为了研究这个想法，我们计划将联合收割机与我们在双光子成像技术方面的专业知识结合起来，在单个神经元和整体水平上探索网络功能，从而揭开自发θ的起源及其与完整网络中感觉输入的相互作用。自发性θ振荡起源的一个强有力的候选机制是肾小球细胞类型（外部簇状细胞（ETC））中的内在起搏，因为已知ETC在θ频率范围内产生自发性活动爆发。因此，在这个项目的第一步是完全建立Ca 2+人口成像肾小球层内的鼻-脑准备，基于预先存在的共振扫描双光子显微镜系统。由于ETC位于靠近延髓表面，并且已知它们的爆发产生大量的Ca 2+内流，因此ETC体细胞信号是Ca 2+成像的极好目标。接下来，我们将研究与局部场电位记录平行的ETCs的自发活动，并通过药理学手段测试它们对θ节律的贡献。最后，我们将探讨感觉刺激与气味，类嗅觉气流和ETC活动之间的耦合，以及主二尖瓣和簇状细胞的平行活动。这种方法将使我们能够调查的生理模式的活动在鼻-脑的准备，从而研究在体外system.In总结，我们的目标是阐明内在的嗅球θ节律的机制，以及它如何相互作用的感觉输入和嗅球输出的主要神经元。我们的研究也可能有助于理解大脑其他区域的theta编码。