Synaptic and circuit mechanisms of olfactory processing

嗅觉处理的突触和电路机制

• 批准号: 7367079
• 负责人: Rachel Wilson
• 金额: $ 40.61万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7367079
• 关键词: Address; Biological Models; Brain; Cells; Chemicals; Chromosome Pairing; Code; Diagnosis; Discrimination; Disease; Drosophila genus; Excitatory Synapse; Genetic; Goals; Human; Individual; Inhibitory Synapse; Insecta; Interneurons; Lateral; Lobe; Malignant neoplasm of lung; Measures; Mediating; Medical; Methods; Neurodegenerative Disorders; Neurons; Neuropil; Nose; Odors; Olfactory Receptor Neurons; Patients; Play; Process; Property; Range; Receptor Gene; Recurrence; Relative (related person); Research Personnel; Role; Sensory; Sensory Process; Shapes; Staging; Stereotyping; Stimulus; Structure; Study models; Synapses; System; Testing; Vertebrates; biodefense; design; fly; genetic manipulation; improved; in vivo; insight; mutant; neural circuit; olfactory bulb; olfactory disorder; olfactory receptor; patch clamp; postsynaptic; presynaptic; programs; receptor; research study; response; sensor; sensory stimulus; stimulus processing; tool

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.

气味分子被嗅觉受体神经元感知，进而发送有关气味的信息 对嗅球（脊椎动物）或触角叶（昆虫）的刺激。所有的受体神经元 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（肾小球） 脑。当嗅觉信息被大脑中的神经回路处理时，接下来会发生什么仍然是 不太了解。一个困难是嗅觉回路的复杂性：每个肾小球都包含 周期性的兴奋性和抑制性神经回路，并接收来自其他肾小球的横向连接。 考虑到可用的遗传工具的范围，果蝇是研究这个问题的一个很好的模型系统 在果蝇中。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 研究检查了触角叶电路如何处理嗅觉信息。尤其， 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 针对单个肾小球的感觉输入中的破坏或救援功能。体内全细胞膜片钳 记录将用于评估 PN 对果蝇触角嗅觉刺激的反应。具体目标 #1 询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 PN 中。目标 #2 检验肾小球之间的抑制性和/或兴奋性突触同时存在的假设 定型且具体。目标 #3 研究每个突触相互作用的贡献 肾小球对 PN 中气味诱发活动的具体特征的影响。这个项目应该贡献 极大地帮助我们理解大脑嗅觉处理的最初步骤。 了解早期嗅觉编码应该有助于治疗人类患者的嗅觉障碍，并且 可能有助于理解为什么这些疾病往往是神经退行性疾病的早期预警信号。 此外，了解大脑如何编码气味为气味的设计提供了宝贵的见解。 所谓的“人造鼻子”，旨在检测和区分特定挥发性化学物质的传感器。 这些传感器在医学诊断和生物防御方面具有重要的应用，并表现出特殊的性能。 通过测量受试者呼吸中存在的化学物质，有望诊断一期肺癌。