Functions of Nicotine Receptors in Sensory Neocortex

描述（由申请人提供）：对于听力，与其他感官一样，对环境刺激的感知随着大脑中尼古丁乙酰胆碱受体（nAChRs）的激活而改善。例如，听觉认知功能通过给药尼古丁得到增强，但通过阻断nachr（使用其他药物）或疾病引起的nachr损失（即，在神经退行性疾病中，如阿尔茨海默病）而受损。因此，人们普遍认为，nachr对最佳的听觉认知功能很重要。因此，尽管人们正在开发尼古丁药物来治疗各种认知障碍，但迄今为止，这种方法还没有被用于治疗听觉处理障碍。在听觉注意过程中，nachr的激活被认为可以改善注意力过滤——增强对重要刺激的处理和对分散刺激的抑制，这似乎涉及听觉系统中频率接受野（rf）的缩小。我们假设nachr的激活会缩小初级听觉皮层（A1）的RF调谐，并增强狭窄RF内的加工，并且nachr的这些细胞作用有助于注意过滤。目的1将确定nachr的激活如何改变光谱积分

DESCRIPTION (provided by applicant): For hearing, as for the other senses, the perception of environmental stimuli improves with activation of nicotinic acetylcholine receptors (nAChRs) in the brain. For example, auditory-cognitive function is enhanced by administration of the drug nicotine, but impaired by blocking nAChRs (using other drugs) or by disease- induced loss of nAChRs (i.e., in neurodegenerative diseases, such as Alzheimer's Disease). It is widely thought, therefore, that nAChRs are important for optimal auditory-cognitive function. Although, as a result, nicotinic drugs are being developed to treat a variety of cognitive disorders, such approaches to date have not been used to treat auditory processing disorders. During auditory attention, activation of nAChRs is thought to improve attentional filtering-the enhanced processing of important stimuli and suppression of distracting stimuli that appears to involve narrowing of frequency receptive fields (RFs) in the auditory system. We hypothesize that activation of nAChRs will narrow RF tuning in primary auditory cortex (A1) and enhance processing within narrowed RFs, and that these cellular actions of nAChRs contribute to attentional filtering. Aim 1 will determine how activation of nAChRs alters spectral integration in A1, using tone-evoked current- source density (CSD) profiles to determine frequency RFs. Aim 2 will determine how nicotinic activation of intracellular signal transduction involving mitogen-activated protein kinase (MAPK) recruits subpopulations of neurons, especially interneurons, in A1. Aim 3 will determine how activating nAChRs and MAPK in identified interneurons alters acoustic processing. These Aims will identify mechanisms by which nAChRs in A1 can enhance auditory processing, and specify the contributions of nAChR subtypes and neuron subpopulations. Our long-term goal is to understand nicotinic mechanisms of auditory-cognitive function, and thereby aid the development of pharmacological treatments for auditory processing disorders.