Compensatory Responses of the Olfactory System to Sensory Deprivation

嗅觉系统对感觉剥夺的补偿反应

• 批准号: 0445793
• 负责人: David Coppola
• 金额: $ 3.9万
• 依托单位: Randolph-Macon College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-15 至 2005-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0445793&HistoricalAwards=false
• 关键词: Compensatory; Responses; Olfactory; System; Sensory

Neural activity, either sensory driven or endogenous, is critical for the development and functional maintenance of many parts of the nervous system. For example, if sensory input is eliminated during a critical period in early life, primary sensory areas in the brain can be malformed, sometimes irreversibly. Given the importance of continued sensory input, it is possible that sensory receptor cells would evolve compensatory responses to sensory deprivation. Recent evidence suggests that neurons in many areas of the nervous system do indeed display homeostatic plasticity such that their overall intrinsic excitability is altered by experience. In the developing olfactory system, surgically occluding one side of the nasal cavity, and thus reducing odor stimulation to olfactory receptor neurons, alters the development of olfactory pathways receiving input from these receptors. Recently, the PI and his colleagues discovered that adenylyl cyclase three (ACIII), olfactory marker protein (OMP), and a phosphodiesterase (PDE4A), all proteins known or suspected to be involved in olfactory transduction or modulation, increase in concentration in olfactory receptor neurons following naris occlusion. These results imply that olfactory neurons, like many other neuron types, have a compensatory response to stimulus deprivation. The funds made available by the NSF will allow the PI to further evaluate this hypothesis. Specifically, electrophysiological equipment will be purchased to allow a comparison between the responses of normal and deprived olfactory sensory cells. If Dr. Coppola's hypothesis is correct, deprived cells should become more responsive to odors. An operant chamber and flow-dilution olfactometer will be purchased to allow behavioral odor thresholds (and other parameters) to be compared between normal and deprived mice. According to his hypothesis, mice deprived of odors should have a decreased threshold compared to control mice as a consequence of their compensatory response. Lastly, consumable supplies will be purchased that will allow preliminary immunocytochemical work on the ACIII, OMP, PDE4A to be confirmed and extended. Taken together the results of these studies will help establish a previously unexplored compensatory mechanism of olfactory receptor neurons, shed light on the role of OMP and PDE4A in odor transduction/modulation and clarify the role of odor deprivation on the developing and adult olfactory system. The broader impact of this project lies in its ability to improve the science infrastructure at Randolph-Macon College.

神经活动，无论是感觉驱动的还是内源性的，对于神经系统的许多部分的发育和功能维持都是至关重要的。例如，如果感觉输入在生命早期的关键时期被消除，大脑中的初级感觉区域可能会畸形，有时是不可逆的。鉴于持续的感觉输入的重要性，感觉感受器细胞可能会对感觉剥夺产生补偿反应。 最近的证据表明，神经系统许多区域的神经元确实显示出稳态可塑性，因此它们的整体内在兴奋性会因经验而改变。在发育中的嗅觉系统中，通过手术封闭鼻腔的一侧，从而减少对嗅觉受体神经元的气味刺激，改变了从这些受体接收输入的嗅觉通路的发育。最近，PI和他的同事们发现，腺苷酸环化酶3（ACIII），嗅觉标记蛋白（OMP）和磷酸二酯酶（PDE 4A），所有已知或怀疑参与嗅觉转导或调制的蛋白质，在鼻孔阻塞后嗅觉受体神经元中的浓度增加。这些结果意味着嗅觉神经元与许多其他神经元类型一样，对刺激剥夺有补偿反应。NSF提供的资金将使PI能够进一步评估这一假设。具体而言，将购买电生理设备，以比较正常和剥夺嗅觉感觉细胞的反应。如果科波拉博士的假设是正确的，那么被剥夺的细胞对气味的反应应该会更灵敏。将购买操作室和流动稀释嗅觉计，以允许在正常和剥夺小鼠之间比较行为气味阈值（和其他参数）。根据他的假设，与对照组小鼠相比，被剥夺气味的小鼠由于其补偿反应而具有降低的阈值。最后，将购买消耗品，以确认和延长ACIII、OMP、PDE 4A的初步免疫细胞化学工作。总之，这些研究的结果将有助于建立一个以前未探索的嗅觉受体神经元的补偿机制，阐明OMP和PDE 4A在气味转导/调节中的作用，并阐明气味剥夺对发育和成年嗅觉系统的作用。该项目更广泛的影响在于它能够改善伦道夫-梅肯学院的科学基础设施。