Presubicular bursting and visual anchoring of the head direction signal

头部方向信号的前下爆发和视觉锚定

• 批准号: 406654673
• 负责人: Professor Dr. Michael Brecht
• 金额: --
• 依托单位: Institut für Biologie
• 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/406654673?language=en
• 关键词: Presubicular; bursting; visual; anchoring; head

Knowing where we are, where we have come from and where we are going is crucial to behavior. Our sense of orientation derives from combining multiple types of sensory information with our memory of known places, and it is closely linked to networks that subserve episodic memory storage throughout life (Buzsáki and Moser 2013). How these networks encode spatial orientation depends strongly on vision, but the cellular and circuit basis for this visual anchoring of our sense of orientation remains unknown.We will focus on the presubiculum, which functions as an internal compass. Cells in the presubiculum code for head direction. This signal originates from the lateral mammillary nucleus (hypothalamus), where vestibular signals are transformed into head-direction signals and are transferred to presubiculum via the anterodorsal thalamic nucleus. This directional signal is anchored to external visual landmark allowing a coherent activity of the network. Presubicular lesions disrupt the control of head-direction signals by visual landmarks. Neurons in the different presubicular layers have distinct targets and we are particularly interested in the direct feedback to the lateral mammillary nucleus, that seems to rely on intrinsic bursting neurons of layer 4 (Yoder et al. 2015; Huang et al. 2017). Our project evolves around the idea that a burst feedback signal has a key role for visual updating of the head direction signal.In this bilateral collaboration between our two laboratories in Paris and Berlin, we aim to elucidate how cells and circuits interact dynamically to produce a visual anchoring for our sense of orientation. This project combines in vivo single-cell physiology during behavior with analysis of cellular properties and microcircuit synaptic connectivity in vitro. We pose the following questions: 1) Does the presubicular feedback to the upstream regions of the head-direction system indeed occur via layer 4 bursting cells in vivo?2) What are the cellular and microcircuit mechanisms leading to layer 4 neuron recruitment and burst firing? 3) What is the signal carried by layer 4 cells and does it reflect the combinations of vestibular and visual sensory inputs? 4) Is presubicular layer 4 bursting required for providing the visual landmark control of the head-direction signal?5) How do the synaptic short-term dynamics of feedback synapses contribute to the relay of feedback signals?The project is timely because of the recent demonstration of an internally organized network of the head-direction sense (Peyrache et al. 2015). What distinguishes our approach from previous studies is that we will combine high-end in vivo recordings with synaptic physiology and optogenetics to elucidate cellular integration of visual and vestibular signals. The tight collaboration of two labs with complementary expertise will enable such bridging between synaptic, cellular and systems neuroscience.

知道我们在哪里，我们从哪里来，我们要去哪里对行为至关重要。我们的方向感来自于将多种类型的感官信息与我们对已知地点的记忆相结合，并且它与整个生命中有助于情景记忆存储的网络密切相关（Buzsáki和Moser 2013）。这些神经网络如何编码空间方位在很大程度上取决于视觉，但我们的方位感的视觉锚定的细胞和电路基础仍然未知，我们将重点关注前下托，它的功能就像一个内部指南针。前下托中的细胞为头部方向编码。该信号起源于外侧乳头体核（下丘脑），在那里前庭信号被转化为头方向信号，并通过丘脑前背核被传递到前下托。该方向信号被锚定到外部视觉地标，从而允许网络的连贯活动。下托前病变破坏了视觉标志对头部方向信号的控制。不同下托前层中的神经元具有不同的靶点，我们对乳头体外侧核的直接反馈特别感兴趣，这似乎依赖于第4层的内在爆发神经元（Yoder et al. 2015; Huang et al. 2017）。我们的项目围绕着突发反馈信号对头部方向信号的视觉更新具有关键作用的想法而发展。在我们位于巴黎和柏林的两个实验室之间的双边合作中，我们的目标是阐明细胞和回路如何动态地相互作用，从而为我们的方向感产生视觉锚定。该项目结合了在体内的单细胞生理学行为与细胞特性和微电路突触连接在体外的分析。我们提出以下问题：（1） 下托前反馈到头向系统的上游区域是否真的通过体内第4层爆裂细胞发生？（二） 导致第4层神经元募集和爆发放电的细胞和微电路机制是什么？第三章 第4层细胞携带的信号是什么？它是否反映了前庭和视觉感官输入的组合？四、 下托前第4层是否需要爆裂来提供头向信号的视觉标志控制？第五章） 反馈突触的突触短期动力学如何对反馈信号的传递做出贡献？该项目是及时的，因为最近演示了头部方向感的内部组织网络（Peyrache et al. 2015）。我们的方法与以前的研究的区别在于，我们将联合收割机结合高端体内记录与突触生理学和光遗传学来阐明视觉和前庭信号的细胞整合。两个具有互补专业知识的实验室的紧密合作将使突触，细胞和系统神经科学之间的桥梁。