Sensory transduction and its synaptic control

感觉转导及其突触控制

• 批准号: RGPIN-2021-02469
• 负责人: Torkkeli, Paivi
• 金额: $ 2.04万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=741996
• 关键词: Sensory; transduction; its; synaptic; control

Our bodies are constantly bombarded by sensory signals such as light, taste, smell, sound, and pain. The brain must process and coordinate incoming sensory information with ongoing activities to execute relevant behavioral tasks. My laboratory studies mechanical senses, such as touch, vibration, and hearing, and we also work on vision. We are especially interested in transduction, the conversion of sensory signals into electrochemical events. This complex process involves multiple molecules, many of which have not yet been identified in any sensory system in any animal. We also aim to learn how sensory cells encode and transmit signals to the central nervous system and how these processes are modulated by efferent synaptic input. We use large spiders, cockroaches and locusts as our model animals because their sensory cells are easily accessible for powerful experimental approaches such as intracellular recordings during mechanical stimulation, unfeasible in common model species because of the small sizes and/or complex locations of their sense organs. An important feature of spiders is extensive efferent synaptic connections to peripheral regions of their mechanosensory cells with neurotransmitters such as GABA and acetylcholine that modulate sensory neurons via multiple receptor types. Similar phenomena only occur in poorly accessible central nervous systems of most other animals. A decade ago, use of powerful molecular methods such as gene sequencing and genetic manipulation were limited to a small number of model species, but they can now be used in a wide variety of organisms. In recent years, we have developed and applied molecular methods to complement our electrophysiological, optical, and computer-based expertise. Our major research aims are to: 1) uncover the molecular machineries behind mechanotransduction within the spider strain detecting mechanosensory neurons and locust auditory neurons; 2) discover whether differences in receptor subunit composition of spider sensory neurons lead to distinct cellular responses to GABA, the main inhibitory neurotransmitter in all animals; 3) explore the physiological roles of the multiple acetylcholine esterase (AChE) enzymes of the spider central and peripheral nervous systems; and 4) decode the molecular pathways that allow nocturnal insects to see in dim light. Mechanical senses and vision are essential for our survival, and their failure causes disabilities such as deafness and blindness, so unraveling the molecular mechanism of transduction is hugely important. Central efferents modulate sensory neurons of all animals, including humans and their dysfunction leads to chronic pain and movement disorders. GABA receptors and AChE are major targets for drugs to treat human diseases such as anxiety and Alzheimer's and many widely used insecticides act on these molecules, thus better understanding of their selectivity can lead to their more rational use and integrated pest management.

我们的身体不断受到光、味觉、嗅觉、声音和疼痛等感官信号的轰炸。大脑必须处理传入的感官信息并将其与正在进行的活动相协调，以执行相关的行为任务。我的实验室研究机械感觉，例如触觉、振动和听觉，我们还研究视觉。我们对转导特别感兴趣，即将感觉信号转化为电化学事件。这个复杂的过程涉及多个分子，其中许多分子尚未在任何动物的任何感觉系统中被识别。我们还旨在了解感觉细胞如何编码并将信号传输到中枢神经系统，以及这些过程如何通过传出突触输入进行调节。我们使用大型蜘蛛、蟑螂和蝗虫作为我们的模型动物，因为它们的感觉细胞很容易进行强大的实验方法，例如机械刺激期间的细胞内记录，这在普通模型物种中是不可行的，因为它们的感觉器官尺寸小和/或位置复杂。蜘蛛的一个重要特征是其机械感觉细胞的外围区域具有广泛的传出突触连接，这些细胞具有 GABA 和乙酰胆碱等神经递质，可通过多种受体类型调节感觉神经元。类似的现象只发生在大多数其他动物的中枢神经系统中。十年前，基因测序和基因操作等强大的分子方法的使用仅限于少数模型物种，但现在它们可以用于多种生物体。近年来，我们开发并应用分子方法来补充我们的电生理学、光学和计算机专业知识。我们的主要研究目标是：1）揭示蜘蛛品系中机械转导背后的分子机制，检测机械感觉神经元和蝗虫听觉神经元； 2) 发现蜘蛛感觉神经元受体亚基组成的差异是否会导致细胞对 GABA（所有动物中主要的抑制性神经递质）产生不同的细胞反应； 3）探索蜘蛛中枢和周围神经系统多种乙酰胆碱酯酶（AChE）的生理作用； 4）解码夜行性昆虫在昏暗光线下能看见东西的分子途径。机械感官和视觉对于我们的生存至关重要，它们的失败会导致耳聋和失明等残疾，因此解开转导的分子机制非常重要。中枢传出神经调节包括人类在内的所有动物的感觉神经元，其功能障碍会导致慢性疼痛和运动障碍。 GABA受体和AChE是治疗焦虑症和阿尔茨海默氏症等人类疾病的药物的主要靶标，许多广泛使用的杀虫剂作用于这些分子，因此更好地了解它们的选择性可以导致更合理的使用和综合害虫治理。