Thalamic reticular nucleus modulation of auditory thalamocortical function

丘脑网状核对听觉丘脑皮质功能的调节

• 批准号: 8951649
• 负责人: DANIEL A LLANO
• 金额: $ 22.33万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-23 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8951649
• 关键词: Acoustics; Action Potentials; Address; Amygdaloid structure; Attention; Auditory; Auditory area; Brain; Brain Part; Calcium; Calcium Channel Blockers; Cell Nucleus; Cells; Cognitive; Development; Disease; Dyslexia; Emotional; Flavoproteins; Future; Hearing; Image; Individual; Inferior Colliculus; Investigation; Lasers; Lead; Light; Literature; Location; Measurement; Measures; Medial geniculate body; Mus; Neurons; Normal Range; Optics; Output; Pathway interactions; Physiology; Play; Population; Prefrontal Cortex; Preparation; Process; Relative (related person); Research Personnel; Role; Schizophrenia; Sensory Process; Series; Signal Transduction; Slice; Structure; Synapses; System; T-Type Calcium Channels; Techniques; Testing; Thalamic structure; Time; Tinnitus; Work; basal forebrain; base; capsule; cognitive function; design; fluorescence imaging; frontal lobe; gamma-Aminobutyric Acid; insight; meetings; neurophysiology; neurotransmission; novel; patch clamp; public health relevance; relating to nervous system; response; selective attention; sound; synaptic depression; targeted treatment; tool; transmission process

 DESCRIPTION (provided by applicant): The thalamic reticular nucleus (TRN) is a capsule of GABAergic neurons that partially envelops the thalamus and has been speculated to play a role in normal cognitive functions, such as selective attention, and in pathological states, such as tinnitus and schizophrenia. Therefore, understanding the function of the auditory portion of the TRN will unlock secrets not only about normal hearing, but also provide insights about how thalamocortical systems become dysfunctional in disease. Unfortunately, the impact of the TRN on sensory processing has been particularly inscrutable because of its small size and deep location. Until now, there has not been an experimental preparation that permitted measurement of thalamic and cortical activity at the cellular level while allowing simultaneous manipulation of the TRN and afferent input to the thalamus. We have recently overcome this hurdle by developing a brain slice preparation in the mouse that contains robust connectivity between the inferior colliculus, auditory thalamus, auditory TRN and the auditory cortex (Llano et al. J Neurophysiology 2014, 111(1):197). Herein, we combine the use of this new preparation with a range of optical, electrophysiological and pharmacological tools to test a novel hypothesis: that the TRN produces paradoxical rate- dependent enhancement of the transmission of neural signals as they pass through the colliculo-thalamocortical pathway. This hypothesis is based upon recent findings that the auditory TRN receives non-reciprocal input from wide-ranging neural structures, such as the frontal cortex and amygdala, and that GABAergic input from the TRN produces short windows of hyperexcitability in thalamic neurons by de-inactivating T-type calcium currents. Successful completion of this work will open the doors to future studies that examine the impact of the frontal cortex and amygdala on auditory thalamocortical systems through the TRN, and therefore will shed light on how cognitive and emotional states influence acoustic processing.

 描述（由申请人提供）：丘脑网状核（TRN）是GABA能神经元的囊，其部分覆盖丘脑，并被推测在正常认知功能（如选择性注意）和病理状态（如耳鸣和精神分裂症）中发挥作用。因此，了解TRN听觉部分的功能不仅可以解开有关正常听力的秘密，还可以提供有关丘脑皮质系统如何在疾病中功能失调的见解。不幸的是，TRN对感觉加工的影响特别难以理解，因为它的尺寸小，位置深。到目前为止，还没有一种实验制剂，允许在细胞水平上测量丘脑和皮层活动，同时允许同时操纵 TRN和丘脑的传入输入。我们最近通过在小鼠中开发脑切片制备物克服了这一障碍，所述脑切片制备物包含下丘、听觉丘脑、听觉TRN和听觉皮层之间的稳健连接（拉诺等人，J Neurophysiology 2014，111（1）：197）。在此，我们结合联合收割机使用这种新的制剂与一系列的光学，电生理和药理学工具来测试一个新的假设：TRN产生矛盾的速率依赖性增强的神经信号的传输，因为它们通过丘-丘脑皮质通路。这一假设是基于最近的发现，即听觉TRN从广泛的神经结构，如额叶皮层和杏仁核，接收非互惠输入，并且来自TRN的GABA能输入通过去失活T型钙电流在丘脑神经元中产生短窗口的过度兴奋。这项工作的成功完成将为未来的研究打开大门，研究额叶皮层和杏仁核通过TRN对听觉丘脑皮层系统的影响，因此将阐明认知和情绪状态如何影响声学处理。