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。该研究结合了旨在进一步验证使用新型电流胆碱检测方法评估乙酰胆碱（ACh）释放的实验，以及将探索该方法用于测试关于皮质胆碱能输入系统兴奋性的可塑性和长期变化的假设的有用性的研究。最初的实验将检验胆碱能基底前脑（BF）的电刺激（包括强电刺激）与听觉皮层中引起的胆碱信号之间的关系。另外的实验将确定所诱发的胆碱信号反映了乙酰胆碱水解产生的胆碱，以及乙酰胆碱释放的去极化依赖性。第二个系列的实验将采用这种方法来检验关于皮层乙酰胆碱释放在BF刺激对听觉皮层输入加工的长期可塑性变化的中介作用的假设。总的来说，这项研究将实现两个主要目标。首先，它将产生关于胆碱生物传感器在高时间（毫秒到秒）和空间（微米）分辨率下评估乙酰胆碱释放的有效性和有用性的必要证据。其次，目前评估乙酰胆碱释放的技术在需要刺激引起的乙酰胆碱释放变化信息的研究中应用有限；然而，这些信息对于检验关于胆碱能传递在调节感觉输入加工中的可塑性变化中的作用的假设是必不可少的。提出的研究将测试使用胆碱微电极技术解决这一核心问题的可行性。此外，预期的结果将有助于未来研究皮层胆碱能输入系统在调节获得行为，特别是情感意义的刺激的注意加工中的作用。

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.