Cholinergic plasticity in auditory input processing

描述（由申请人提供）：此小额资助申请要求支持涉及新研究技术和研究方法开发的研究。拟议的研究结合实验设计，以进一步验证使用一种新的电流胆碱检测方法的评估乙酰胆碱（ACh）释放的研究，将探讨这种方法的有用性的假设测试有关的功能塑料，长期变化的兴奋性的皮层胆碱能输入系统。最初的实验将检查电，包括强直，刺激胆碱能基底前脑（BF）和诱发的胆碱信号在听觉皮层之间的关系。另外的实验将确定，诱发胆碱信号反映胆碱来自水解乙酰胆碱，并从乙酰胆碱释放去极化依赖性。第二个系列的实验将采用这种方法来测试假设皮层乙酰胆碱释放的作用，在调解的长期塑料变化的BF刺激听觉皮层输入处理。总的来说，这项研究将实现两个主要目标。首先，它将产生重要的证据有关的有效性和有用性的胆碱生物传感器的评估ACh释放在高的时间（毫秒到秒）和空间（微米）分辨率。第二，目前的技术用于评估乙酰胆碱释放是有限的使用的研究需要刺激诱发的乙酰胆碱释放的变化的信息，但是，这样的信息是必不可少的胆碱能传递介导的塑料变化的作用，在感觉输入处理的假说的测试。拟议的研究将测试使用胆碱微电极技术来解决这一核心问题的可行性。此外，预期的结果将是有用的，为未来的调查的作用，皮层胆碱能输入系统在调节注意处理的刺激，获得行为，特别是情感，意义。

DESCRIPTION (provided by applicant): This Small Grant Application requests support for research involving the development of new research technology and research approaches. The proposed research combines experiments designed to validate further the use of a novel amperometric choline detection method for the assessment of acetylcholine (ACh) release with studies that will explore the usefulness of this methodology for the test of hypotheses about the functions of plastic, long-term changes of the excitability of the cortical cholinergic input system. The initial experiments will examine the relationships between electrical, including tetanic, stimulation of the cholinergic basal forebrain (BF) and evoked choline signals in the auditory cortex. Additional experiments will determine that evoked choline signals reflect choline derived from hydrolysis of ACh, and from ACh released depolarization-dependently. A second series of experiments will employ this methodology to test hypotheses about the role of cortical ACh release in the mediation of the long-term plastic changes of BF stimulation on auditory cortical input processing. Collectively, this research will achieve two major goals. First, it will generate essential evidence concerning the validity and usefulness of the choline biosensor for the assessment of ACh release at high temporal (milliseconds to seconds) and spatial (um) resolution. Second, present techniques for the assessment of ACh release are of limited use for research requiring information about stimulus-evoked changes in ACh release; however, such information is essential for the test of hypotheses about the role of cholinergic transmission in mediating plastic changes in sensory input processing. The proposed research will test the viability of using the choline microelectrode technique to address this central issue. Moreover, the expected results will be useful for future investigations about the role of the cortical cholinergic input system in modulating the attentional processing of stimuli that acquire behavioral, specifically affective, significance.