Functions of Nicotine Receptors in Sensory Neocortex

感觉新皮质尼古丁受体的功能

• 批准号: 8598620
• 负责人: Raju Metherate
• 金额: $ 34.87万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8598620
• 关键词: Acoustics; Alzheimer' s Disease; Attention; Auditory; Auditory Perceptual Disorders; Auditory area; Auditory system; Brain; Characteristics; Cognition Disorders; Cognitive; Cortical Column; Data; Development; Disease; Disinhibition; Distant; Dose; Electrophysiology (science); Environment; Exhibits; Frequencies; Genetic; Goals; Green Fluorescent Proteins; Hearing; Human; Image; In Vitro; Interneurons; Label; Lateral; Lead; Life; Mediating; Mitogen-Activated Protein Kinases; Modality; Mus; Muscimol; Neocortex; Neurodegenerative Disorders; Neurons; Nicotine; Nicotinic Agonists; Nicotinic Receptors; Noise; Pathway interactions; Perception; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Play; Process; Recruitment Activity; Regulation; Relative (related person); Rodent; Role; Sensory; Signal Transduction; Somatostatin; Source; Spatial Distribution; Specific qualifier value; Speech; Stimulus; Synapses; System; Testing; Whole-Cell Recordings; cognitive function; density; distraction; hippocampal pyramidal neuron; improved; in vivo; notch protein; postsynaptic; presynaptic; public health relevance; receptive field; receptor; response; sound; therapeutic development; two-photon; Acoustics; Alzheimer' s Disease; Attention; Auditory; Auditory Perceptual Disorders; Auditory area; Auditory system; Brain; Characteristics; Cognition Disorders; Cognitive; Cortical Column; Data; Development; Disease; Disinhibition; Distant; Dose; Electrophysiology (science); Environment; Exhibits; Frequencies; Genetic; Goals; Green Fluorescent Proteins; Hearing; Human; Image; In Vitro; Interneurons; Label; Lateral; Lead; Life; Mediating; Mitogen-Activated Protein Kinases; Modality; Mus; Muscimol; Neocortex; Neurodegenerative Disorders; Neurons; Nicotine; Nicotinic Agonists; Nicotinic Receptors; Noise; Pathway interactions; Perception; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Play; Process; Recruitment Activity; Regulation; Relative (related person); Rodent; Role; Sensory; Signal Transduction; Somatostatin; Source; Spatial Distribution; Specific qualifier value; Speech; Stimulus; Synapses; System; Testing; Whole-Cell Recordings; cognitive function; density; distraction; hippocampal pyramidal neuron; improved; in vivo; notch protein; postsynaptic; presynaptic; public health relevance; receptive field; receptor; response; sound; therapeutic development; two-photon

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.

描述（由申请人提供）：对于听力，与其他感觉有关，环境刺激的感知会随着大脑中烟碱乙酰胆碱受体（NACHR）的激活而改善。例如，通过施用药物尼古丁，可以增强听觉认知功能，但通过阻止NACHR（使用其他药物）或疾病诱发的NACHRS（即在神经退行性疾病中，例如阿尔茨海默氏病）受损。因此，人们普遍认为NACHR对于最佳的听觉认知功能很重要。尽管如此，正在开发烟碱药物来治疗多种认知障碍，但迄今为止，这种方法尚未用于治疗听觉处理障碍。在听觉关注期间，人们认为NACHR的激活可以改善注意力过滤 - 增强了重要刺激的处理以及对分散刺激的抑制，这似乎涉及听觉系统中频率接受场（RFS）的缩小。我们假设NACHR的激活将在原代听觉皮层（A1）中缩小RF调整，并增强狭窄的RF内的处理，并且NACHR的这些细胞作用有助于注意力过滤。 AIM 1将决定NACHRS的激活如何改变光谱整合 A1，使用Tone诱发的电流源密度（CSD）轮廓来确定频率RF。 AIM 2将确定涉及有丝分裂原激活蛋白激酶（MAPK）的细胞内信号转导的烟碱激活如何募集A1中神经元的亚群，尤其是中间神经元。 AIM 3将确定在已识别的中间神经元中激活NACHR和MAPK如何改变声学处理。这些目标将确定A1中NACHR可以增强听觉处理的机制，并指定NACHR亚型和神经元亚群的贡献。我们的长期目标是了解听觉认知功能的烟碱机制，从而有助于开发用于听觉处理障碍的药理治疗方法。