Sensory transduction and its synaptic control

我们的身体不断受到感官信号的轰炸，如光，味道，气味，声音和疼痛。大脑必须处理和协调传入的感官信息与正在进行的活动，以执行相关的行为任务。我的实验室研究机械感官，如触觉、振动和听觉，我们也研究视觉。我们特别感兴趣的是转导，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。我们的目标还在于了解感觉细胞如何编码和传递信号到中枢神经系统，以及这些过程如何被传出突触输入调制。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获得强大的实验方法，如在机械刺激过程中的细胞内记录，在常见的模型物种中是不可行的，因为它们的感觉器官的尺寸小和/或位置复杂。蜘蛛的一个重要特征是与其机械感觉细胞的外周区域的广泛传出突触连接，神经递质如GABA和乙酰胆碱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难以接近的中枢神经系统中。十年前，基因测序和遗传操作等强大的分子方法仅限于少数模式物种，但它们现在可以用于各种生物。近年来，我们已经开发和应用分子方法，以补充我们的电生理学，光学和基于计算机的专业知识。我们的主要研究目标是：1）揭示蜘蛛品系机械感觉神经元和蝗虫听觉神经元中机械传导的分子机制; 2）发现蜘蛛感觉神经元受体亚基组成的差异是否导致对GABA（所有动物中主要的抑制性神经递质）的不同细胞反应; 3）探索蜘蛛中枢和外周神经系统的多种乙酰胆碱酯酶（AChE）的生理作用; 4）解码使夜间昆虫在昏暗光线下看到的分子途径。机械感觉和视觉对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。中枢传出神经调节所有动物（包括人类）的感觉神经元，其功能障碍导致慢性疼痛和运动障碍。GABA受体和乙酰胆碱酯酶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点，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它们更合理的使用和综合害虫管理。

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.