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.

气味分子是通过嗅觉受体神经元感测的，嗅觉受体神经元又发送有关气味的信息 刺激嗅球（脊椎动物）或触角叶（昆虫）。所有受体神经元 表达相同的嗅觉受体基因将信息发送到同一离散区域（肾小球） 脑。接下来发生的事情是在脑电路中处理嗅觉信息时的 理解不佳。一个困难是嗅觉电路的复杂性：每个肾小球都包含 复发性兴奋性和抑制性神经回路，并接收其他肾小球的侧向连接。 鉴于可用的遗传工具范围，果蝇是研究此问题的良好模型系统 在果蝇中。同样，苍蝇嗅觉系统与脊椎动物大致相似，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（称为投影神经元或PNS），使用特定的遗传操纵 在靶向单个肾小球的感觉输入中破坏或救援功能。体内全细胞贴片钳 记录将用于评估对蝇触角嗅觉刺激的PN响应。具体目标 ＃1询问肾小球之间的抑制性和兴奋性突触是否有助于气味诱发活性 在PNS中。 AIM＃2检验了肾小球之间抑制性和/或兴奋性突触的假设都是 定型和具体。 AIM＃3调查了每个内部突触相互作用的贡献 肾小球符合PNS中气味诱发活性的特定特征。这个项目应该做出贡献 基本上是我们理解大脑嗅觉处理的第一步。 了解早期的嗅觉编码应有助于治疗人类患者的嗅觉疾病，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预警信号。 此外，了解大脑如何编码气味为设计贡献了宝贵的见解 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幻想中具有重要的应用，并显示了特定的 通过测量受试者呼吸中存在的化学物质来诊断1阶段肺癌的承诺。