Neuromodulation in the auditory system

描述（由申请人提供）：理解言语依赖于听觉系统准确表达突出声音的能力。这种表现可能被多种因素改变，包括涉及神经调节系统的疾病。例如，帕金森氏症患者有语言处理问题，这表明多巴胺改变了这些显著信号的正常表现。本研究的重点是多巴胺在改变下丘（IC）显著声音表征中的作用。IC是调节显著信号的听觉处理的主要位置，因为它接收来自多个听觉和非听觉来源的输入，它包含多巴胺受体和纤维，本提案的初步数据表明多巴胺调节IC的听觉反应。本提案的目的是确定多巴胺改变IC中发声表征的机制。第一个目标将在清醒小鼠IC中使用药物在体内单单位记录，以确定多巴胺受体激活对发声反应的影响。第二个目标将使用小鼠IC脑切片的全细胞记录来确定多巴胺对不同神经元类型的内在和突触特性的影响。第三个目标将使用体内全细胞记录

DESCRIPTION (provided by applicant): Understanding speech depends on the capacity of the auditory system to accurately represent salient sounds. This representation may be altered by a variety of factors, including disorders involving neuromodulatory systems. For example, patients with Parkinson's disease have speech processing problems suggesting that dopamine alters normal representation of these salient signals. The proposed studies focus on the role of dopamine in altering representation of salient sounds in the inferior colliculus (IC). The IC is a prime location for modulating auditory processing of salient signals because it receives input from multiple auditory and non-auditory source, it contains dopamine receptors and fibers, and preliminary data from this proposal indicate that dopamine modulates IC auditory responses. The objective of this proposal is to determine the mechanisms by which dopamine alters the representation of vocalizations in IC. The first Aim will use in vivo single unit recordings with application of pharmacological agents in the IC of awake mice to determine the effects of dopamine receptor activation on responses to vocalizations. The second Aim will use whole-cell recordings in mouse IC brain slices to determine the effects of dopamine on intrinsic and synaptic properties of different neuron types. The third Aim will use in vivo whole-cell recordings to identify how intrinsic properties of different neuron types shape selectivity to vocalizations. Aims 1-3 will thus provide an integrated understanding of the cellular and synaptic mechanisms underlying auditory responses to complex sounds. The fourth Aim will determine the sources of dopaminergic input to the IC, an important step towards understanding the behavioral contexts that elicit dopamine release into the IC. The significance of this proposal is that it is the first integrated study of the effects of dopamine on the cellular, synaptic and circuit properties underlying IC responses to salient sounds. The results will increase our mechanistic understanding of auditory processing of meaningful sounds and how this encoding changes with different social contexts, physiological states and communication disorders. These studies using mice with normal hearing will facilitate future studies of genetically engineered mice to further probe the mechanisms underlying specific communication and neurological disorders.