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: 9096739
• 负责人: DANIEL A LLANO
• 金额: $ 19.83万
• 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 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9096739
• 关键词: Acoustics; Action Potentials; Address; Amygdaloid structure; Attention; Auditory; Auditory area; Brain; Calcium; Calcium Channel Blockers; Cell Nucleus; Cells; Cognitive; Development; Disease; Dyslexia; Electrophysiology (science); Emotional; Flavoproteins; Future; Health; 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; 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; 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(申请人提供)：丘脑网状核(TRN)是部分包裹丘脑的GABA能神经元的胶囊，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将揭开正常听力的秘密，还将为丘脑皮质系统如何在疾病中变得功能失调提供见解。不幸的是，TRN对感觉加工的影响尤其令人费解，因为它的体积小，位置深。到目前为止，还没有一种实验准备可以在细胞水平上测量丘脑和皮质的活动，同时允许同时操作 TRN和丘脑的传入传入。我们最近已经克服了这一障碍，在小鼠身上开发了一种脑片制剂，它包含了下丘、听觉丘脑、听觉TRN和听觉皮质之间的强大连接(Llano等人。神经生理学杂志，2014,111(1)：197)。在这里，我们将这种新制剂的使用与一系列光学、电生理和药理学工具相结合来检验一个新的假设：当神经信号通过丘脑-丘脑皮质通路时，TRN产生矛盾的速率依赖的增强神经信号的传递。这一假说基于最近的发现，即听觉TRN接受来自广泛神经结构的非互惠输入，如额叶皮质和杏仁核，来自TRN的GABA能输入通过去激活T型钙电流在丘脑神经元产生短窗口的超兴奋性。这项工作的成功完成将为未来的研究打开大门，这些研究将通过TRN检查额叶皮质和杏仁核对听觉丘脑皮质系统的影响，从而揭示认知和情绪状态如何影响声音处理。