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

基本信息

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
项目类别：
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

项目摘要

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，部分包裹丘脑，推测在正常认知功能（例如选择性注意力）和病理状态（例如因此，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，还可以提供有关如何正常听力的见解。不幸的是，由于 TRN 体积小且位置较深，丘脑皮层系统在疾病中变得功能失调，因此其对感觉处理的影响尤其难以理解。细胞水平，同时允许同时操纵我们最近通过在小鼠中开发一种脑切片制剂克服了这一障碍，该脑切片制剂包含下丘、听觉丘脑、听觉 TRN 和听觉皮层之间的强大连接（Llano 等人，《神经生理学》2014 年）。，111(1):197)，我们将这种新制剂与一系列光学、电生理学和药理学工具结合起来测试一个新的假设：当神经信号通过丘脑皮质通路时，TRN 会产生反常的速率依赖性增强。这一假设基于最近的发现，即听觉 TRN 接收来自广泛神经结构的非交互输入。额叶皮层和杏仁核，以及来自 TRN 的 GABA 能输入通过使 T 型钙电流失活，在丘脑神经元中产生短暂的过度兴奋期。这项工作将为未来的研究打开大门，通过 TRN 检查额叶皮层和杏仁核对听觉丘脑皮层系统的影响，从而揭示认知和情绪状态如何影响声音处理。