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

描述（由申请人提供）：理解感觉表征如何在大脑中转化是神经科学的一个基本问题。解决这个问题的一个重要步骤是理解神经回路中执行这些转换的突触相互作用。尽管在体外对突触传递进行了许多研究，但目前尚不清楚突触计算的哪些方面在体内对编码在spike序列中的自然感觉信息的转化至关重要。这个项目在果蝇的触角叶中解决了这个问题，在那里有可能表征在被识别的神经元之间形成的突触的生理学，这些神经元对自然刺激的反应在体内被很好地记录下来。果蝇的触角叶类似于脊椎动物的嗅球，由形态学上离散的称为肾小球的模块组成，其中嗅觉受体神经元（orn）的轴突与投射神经元（PNs）的树突进行突触接触。局部中间神经元（LNs）连接多个肾小球。先前的研究已经在体内描述了orn和PNs的气味诱发反应，因此在该大脑区域发生的感觉转换开始被理解。本项目研究这些感觉转换背后的突触机制。ORN-PN突触传递将通过在电刺激嗅觉神经的同时记录已识别的pn来表征。pn和LNs之间的肾小球间相互作用将通过遗传编码的“触发器”来表征，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。Specific Aim #1测试了一种假设，即ORN-PN突触的特定特性部分解释了触角叶嗅觉转化的几个关键特征。特异性目的2验证了ORN-PN突触传递的某些特征在肾小球间具有异质性的假设。特异性目的#3验证了PNs和LNs在肾小球间相互作用的假设。这项研究对理解大脑中的感觉处理有很大的帮助。具体来说，它应该有助于我们理解特定突触特性在感觉计算中的作用。反过来，这应该为突触传递缺陷（突触病变）的研究提供信息，这些缺陷会影响大脑的特定感觉区域，并可能最终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预防虫媒疾病的传播。

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.