Biophysics of forward and lateral connections in a genetically-tractable circuit

描述(由申请人提供)：了解感觉表征如何在大脑中转化是神经科学中的一个基本问题。解决这个问题的一个重要步骤是了解执行这些转换的神经回路中的突触相互作用。尽管在体外对突触传递进行了许多研究，但仍不清楚突触计算的哪些方面在体内转换棘波序列中编码的自然感觉信息方面起关键作用。这个项目在果蝇的触角叶中解决了这个问题，在那里有可能描述识别出的神经元之间产生的突触的生理学特征，这些神经元对自然刺激的反应在体内得到了很好的记录。果蝇的触角叶是脊椎动物嗅球的类似物，由称为小球的形态离散的模块组成，嗅觉感受器神经元的轴突与投射神经元的树突进行突触接触。局部中间神经元(LNS)连接多个肾小球。以前的研究已经确定了在活体内来自Orns和PNS的气味诱发反应，因此，人们开始了解发生在这个大脑区域的感觉变化。这个项目研究了这些感觉转换背后的突触机制。On-PN突触传递的特点是在电刺激嗅神经的同时记录已识别的PNS。PNS和LNS之间的肾小球间相互作用将使用遗传编码的“触发器”来描述，以选择性地刺激大脑中的特定神经元，同时记录其他遗传标记的神经元。特殊目的#1验证了这样一个假设，即ORN-PN突触的特殊性质部分解释了触角叶嗅觉转换的几个关键特征。特殊目的#2验证了ORN-PN突触传递的某些特征在肾小球之间是异质性的假设。特殊目的#3测试PNS和LNS跨肾小球相互作用的假设。这项研究应该对理解大脑中的感觉处理有很大的帮助。具体地说，它应该帮助我们理解特定突触属性在感觉计算中的作用。这反过来将为影响大脑特定感觉区域的突触传递缺陷(突触病变)的研究提供信息，并最终可能有助于寻找分子干预措施来补救这些缺陷。此外，对昆虫嗅觉的研究应该有助于我们了解和防止虫媒疾病的传播。

DESCRIPTION (provided by applicant): Understanding how sensory representations are transformed in the brain is a fundamental problem in neuroscience. An important step in solving this problem is understanding the synaptic interactions within the neural circuit that carries out these transformations. Despite many studies of synaptic transmission in vitro, it remains unclear specifically which aspects of synaptic computation are critical in transforming natural sensory information encoded in spike trains in vivo. This project addresses this question in the Drosophila antennal lobe, where it is possible to characterize the physiology of synapses made between identified neurons whose responses to natural stimuli are well documented in vivo. The Drosophila antennal lobe, an analogue of the vertebrate olfactory bulb, consists of morphologically discrete modules called glomeruli, where axons of olfactory receptor neurons (ORNs) make synaptic contacts with the dendrites of projection neurons (PNs). Local interneurons (LNs) interconnect multiple glomeruli. Prior investigations have already characterized odor-evoked responses from both ORNs and PNs in vivo, and as a result the sensory transformations that occur in this brain region are beginning to be understood. This project examines the synaptic mechanisms underlying these sensory transformations. ORN-PN synaptic transmission will be characterized by recording from identified PNs while electrically stimulating the olfactory nerve. Interglomerular interactions among PNs and LNs will be characterized using genetically encoded "triggers" to selectively stimulate specific neurons in the brain while recording from other genetically-labeled neurons. Specific Aim #1 tests the hypothesis that the specific properties of ORN-PN synapses partially explain several key features of olfactory transformation in the antennal lobe. Specific Aim #2 tests the hypothesis that some characteristics of ORN-PN synaptic transmission are heterogeneous across glomeruli. Specific Aim #3 tests the hypothesis that PNs and LNs interact with each other across glomeruli. This study should substantially contribute to understanding sensory processing in the brain. Specifically, it should help us understand the role of specific synaptic properties in sensory computations. This in turn should inform the study of defects in synaptic transmission (synaptopathies) that affect specific sensory regions in the brain, and may ultimately be useful in the search for molecular interventions to remedy these defects. In addition, research into insect olfaction should help us understand and prevent the spread of insect-borne diseases.