The function of thalamic inhibition in auditory processing

丘脑抑制在听觉处理中的作用

• 批准号: 10349497
• 负责人: Solymar Rolon-Martinez
• 金额: $ 3.33万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-09 至 2022-09-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10349497
• 关键词: Acoustics; Affect; Anatomy; Architecture; Auditory; Auditory area; Brain; Cell Nucleus; Cells; Communication; Complex; D Cells; Development; Dorsal; Electrophysiology (science); Environment; Exhibits; Feedback; Frequencies; Goals; Head; Higher Order Chromatin Structure; Imaging Techniques; Immunohistochemistry; Lasers; Measures; Medial; Medial geniculate body; Mus; Neurons; Neurotransmitters; Parvalbumins; Patients; Pattern; Presbycusis; Process; Property; Reporter; Research; Shapes; Somatostatin; Source; Structure; Techniques; Testing; Thalamic Nuclei; Thalamic structure; Tracer; Transgenic Mice; Transgenic Organisms; Viral; Virus; anatomical tracing; auditory pathway; auditory processing; auditory thalamus; awake; cell type; confocal imaging; excitatory neuron; hearing impairment; improved; inhibitory neuron; neuronal circuitry; novel; optogenetics; response; sound; sound frequency; virus genetics

PROJECT SUMMARY The function of thalamic inhibition in auditory processing. Interactions between inhibitory and excitatory neurons along the auditory pathway shape how acoustic information is processed in the brain. The thalamic reticular nucleus (TRN) is the main source of inhibition in the thalamus; it sends dense inhibitory projections to thalamic nuclei including a key structure in the ascending auditory pathway, the medial geniculate body (MGB). MGB is comprised of excitatory thalamic relay cells that project to the auditory cortex (AC) wherein auditory information is then decoded. Additionally, the MGB relay cells send collaterals to TRN to provide feedback. Although TRN is necessary for transfer of important acoustic information to higher-order structures in the auditory pathway, TRN's function at the cellular level in remains poorly characterized. The goal of this proposal is to identify the function of different inhibitory neuronal subtypes in TRN in auditory processing. TRN is comprised entirely of GABAergic inhibitory neurons, of which the two dominant sub-classes are parvalbumin- (PV) and somatostatin- (SOM) positive neurons, with a subset of TRN neurons co-expressing both neurotransmitters. In AC, PV and SOM neurons differentially modulate frequency-dependent responses and differentially control adaptation in excitatory cortical neurons. However, to date, little is known of the function of these two inhibitory neuronal subtypes in the TRN. Moreover, their anatomical characterization remains limited. In this proposal, I will test the hypothesis that PV and SOM neurons in TRN target distinct sub-nuclei of the MGB, exhibit unique sound-response properties, and differentially modulate sound responses in MGB. To test this hypothesis, I will combine state- of-the-art anatomical tracing, optogenetic, and electrophysiological approaches. With novel tracing techniques, I will establish the anatomical connectivity between PV+ and SOM+ neurons of TRN and the MGB. Furthermore, I will use optogenetics and electrophysiological approaches to functionally characterize how PV and SOM neurons of TRN are modulating sound responses in the MGB. Combined, these results will reveal critically important information about the differential function of inhibitory neurons at the level of the auditory thalamus, an essential processing station in the auditory pathway.

项目摘要 丘脑抑制在听觉加工中的作用。 沿着听觉通路的抑制性和兴奋性神经元之间的相互作用塑造了声学 信息在大脑中处理。丘脑网状核（TRN）是抑制的主要来源， 丘脑;它发送密集的抑制性投射到丘脑核团，包括一个关键结构，在上升 听觉通路，内侧膝状体（MGB）。MGB由兴奋性丘脑中继细胞组成， 投射到听觉皮层（AC），然后在其中对听觉信息进行解码。此外，MGB继电器 细胞向TRN发送侧支以提供反馈。虽然TRN是必要的传输重要的声学 在听觉通路中，TRN的功能在细胞水平上仍然存在， 特征不佳。本提案的目的是确定不同抑制剂的功能， TRN中的神经元亚型在听觉处理中的作用。TRN完全由GABA能抑制剂组成， 神经元，其中两个主要亚类是小白蛋白（PV）和生长抑素（SOM）阳性 神经元，其中TRN神经元的子集共表达两种神经递质。AC、PV和SOM神经元 差异调节频率依赖性反应和差异控制兴奋性适应 皮质神经元然而，到目前为止，这两种抑制性神经元亚型的功能知之甚少， 的TRN。此外，它们的解剖学特征仍然有限。在这份提案中，我将检验 TRN中的PV和SOM神经元靶向MGB的不同亚核，表现出独特的声音反应 特性，并在MGB中差分调制声音响应。为了验证这个假设，我将联合收割机状态- 最先进的解剖追踪、光遗传学和电生理学方法。利用新的追踪技术， 我将建立TRN和MGB的PV+和SOM+神经元之间的解剖连接。此外，委员会认为， 我将使用光遗传学和电生理学的方法来功能性地表征PV和SOM如何 TRN的神经元调节MGB中的声音反应。综合起来，这些结果将揭示出 关于在听觉丘脑水平上抑制性神经元的不同功能的重要信息， 听觉通路中的一个重要处理站。