Presubicular bursting and visual anchoring of the head direction signal

知道我们在哪里，我们从哪里来，我们要去哪里，对我们的行为至关重要。我们的方向感来自于将多种类型的感觉信息与我们对已知地点的记忆结合在一起，它与贯穿整个生命的情节记忆存储的网络密切相关(Buzsáki和Moser 2013)。这些网络如何编码空间方位在很大程度上依赖于视觉，但这种视觉定位的细胞和电路基础仍不清楚。我们将重点放在作为内部指南针的小脑前。基底节前的细胞编码头部的方向。这一信号起源于乳房外侧核(下丘脑)，在那里前庭信号被转化为头部方向的信号，并通过丘脑前背侧核传递到丘脑前束前。该定向信号被固定在外部可视地标上，从而允许网络的一致活动。丘疹前病变通过视觉标志扰乱对头部方向信号的控制。不同丘前层的神经元有不同的靶点，我们对直接反馈到外侧乳头状核特别感兴趣，这似乎依赖于第4层的固有爆裂神经元(Yoder等人)。2015年；黄等人。2017年)。我们的项目围绕突发反馈信号对头部方向信号的视觉更新具有关键作用这一想法展开。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电路如何动态相互作用，为我们的方向感产生视觉锚定。该项目将体内单细胞行为生理学与体外细胞特性和微回路突触连接分析相结合。我们提出了以下问题：1)活体中是否真的通过第四层爆裂细胞对头部方向系统上游区域进行睫状体前反馈？2)导致第四层神经元招募和猝发放电的细胞和微电路机制是什么？3)第四层细胞携带的信号是什么，它是否反映了前庭和视觉感觉输入的组合？4)第四层前脉冲波是提供头部方向信号的视觉里程碑控制所必需的吗？5)反馈突触的突触短期动力学如何有助于反馈信号的传递？该项目是及时，因为最近显示了一个内部组织的头部方向感网络(Peyrache等人)。2015年)。我们的方法与以前的研究不同的是，我们将结合高端的活体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这种桥梁成为可能。

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.