Synaptic and circuit mechanisms of olfactory processing

气味分子是由嗅觉感受器神经元感知的，而嗅觉感受器神经元又发送关于气味的信息 刺激嗅球(脊椎动物)或触角叶(昆虫)。所有的感受器神经元 表达相同的嗅觉受体基因将信息发送到大脑中相同的离散区域(小球) 大脑。当嗅觉信息被大脑中的神经回路处理时，接下来发生的事情仍然是 人们对此知之甚少。困难之一是嗅觉回路的复杂性：每个肾小球都含有 重复的兴奋性和抑制性神经回路，并接受来自其他肾小球的侧向联系。 考虑到可用遗传工具的范围，果蝇是研究这个问题的一个很好的模型系统 在果蝇里。此外，苍蝇的嗅觉系统与脊椎动物的嗅觉系统大致相似，但要简单得多。这 这项研究考察了嗅觉信息是如何由触角叶的电路处理的。特别是， 这些实验将剖析二阶嗅觉的气味诱发的电生理反应。 触角叶中的神经元(称为投射神经元，或PN)，使用特定的遗传操作， 破坏或挽救针对单个肾小球的感觉输入功能。活体全细胞膜片钳 记录将被用来评估对苍蝇触角的嗅觉刺激的PN反应。特定目标 #1问肾小球之间的抑制性和兴奋性突触是否都有助于气味诱发的活动 在PNS中。目的#2测试的假设是肾小球之间的抑制性和/或兴奋性突触 刻板的和具体的。目标#3研究了每个突触相互作用的贡献 肾小球对三叉神经痛气味诱发活动的特异性。这个项目应该做出贡献 这在很大程度上有助于我们对大脑中嗅觉处理的第一步的理解。 了解早期的嗅觉编码应该有助于治疗人类患者的嗅觉障碍，以及 可以帮助理解为什么这些疾病通常是神经退行性疾病的早期预警信号。 此外，了解大脑是如何编码气味的，对设计 所谓的“人造鼻子”是一种传感器，旨在检测和区分特定的挥发性化学物质。 这些传感器在医学诊断和生物防御方面有着重要的应用，并表现出独特的性能。 通过测量受试者呼吸中存在的化学物质，有望诊断出第一期肺癌。

Odor molecules are sensed by olfactory receptor neurons, which in turn send information about odor stimuli to the olfactory bulb (in vertebrates), or the antennal lobe (in insects). All the receptor neurons that express the same olfactory receptor gene send information to the same discrete region (glomerulus) in the brain. What happens next-when olfactory information is processed by neural circuits in the brain-is still poorly understood. One difficulty is the complexity of the olfactory circuit: each glomerulus contains recurrent excitatory and inhibitory neural circuits, and receives lateral connections from other glomeruli. Drosophila is a good model system for investigating this problem, given the range of genetic tools available in the fruit fly. Also, the fly olfactory system is broadly similar to that of vertebrates, but much simpler. This study examines how olfactory information is processed by the circuitry of the antennal lobe. In particular, these experiments will dissect the odor-evoked electrophysiological response of second-order olfactory neurons in the antennal lobe (termed projection neurons, or PNs), using specific genetic manipulations that destroy or rescue function in the sensory inputs targeting single glomeruli. In vivo whole-cell patch-clamp recordings will be used to assess PN responses to olfactory stimulation of the fly's antennae. Specific aim #1 asks whether both inhibitory and excitatory synapses between glomeruli contribute to odor-evoked activity in PNs. Aim #2 tests the hypothesis that inhibitory and/or excitatory synapses between glomeruli are both stereotyped and specific. Aim #3 investigates the contribution of synaptic interactions within each glomerulus to the specific features of odor-evoked activity in PNs. This project should contribute substantially to our understanding of the very first steps of olfactory processing in the brain. Understanding early olfactory coding should help in treating olfactory disorders in human patients, and could aid in understanding why these disorders are often early warning signs of neurodegenerative diseases. Furthermore, understanding how the brain encodes odors has contributed valuable insights to the design of so-called "artificial noses", sensors designed to detect and discriminate between specific volatile chemicals. These sensors have important applications in medical diagnosis and biodefense, and have shown particular promise in diagnosing stage 1 lung cancer by measuring the chemicals present in a subject's breath.