Functional Neuroanatomy of the Basolateral Amygdala

基底外侧杏仁核的功能神经解剖学

• 批准号: 7102774
• 负责人: DONALD G RAINNIE
• 金额: $ 24.62万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102774
• 关键词: Macaca mulatta; action potentials; amygdala; brain electrical activity; brain mapping; calcium binding protein; cell cell interaction; cell population study; immunocytochemistry; interneurons; laboratory rat; membrane potentials; mood disorders; neural information processing; neurons; prefrontal lobe /cortex; psychopathology; species difference; voltage /patch clamp

DESCRIPTION (provided by applicant): The amygdala plays a critical role in processing affective stimuli. In humans, imaging studies suggest that reciprocal interactions between the amygdala and prefrontal cortex (PFC) may be associated with cortical control of affect. Significantly, only the basolateral nucleus of the amygdala (BLA) has marked reciprocal connections with the PFC, and in response to affective stimuli firing activity in the BLA precedes firing activity in the PFC. Moreover, during fear conditioning, firing activity in neurons of the BLA and PFC becomes synchronized. Synchronized oscillations in neural networks are thought to represent a "binding" mechanism that rapidly links spatially distant structures, and it is our contention that synchronized activity in the BLA and PFC provides a mechanism by which the emotional valence of sensory stimuli can be rapidly evaluated. Abnormal cortical synchrony has been observed in schizophrenia, autism, PTSD and depression. In order to understand the role of abnormal synchrony in the etiology of affective disorders, we must first understand how synchronized activity normally develops in areas like the BLA. However, little is known of the processes by which the activity of local ensembles of BLA projection neurons (PNs) may become synchronized, let alone how phase synchrony is achieved between the BLA and PFC. We will directly address this knowledge gap by systematically examining the physiological and neuroanatomical substrates that contribute to oscillatory and synchronous activity in BLA PNs. More specifically, we will test the hypothesis that: a) intrinsic membrane currents endow BLA PNs with a "resonant frequency" that predisposes the neurons to fire rhythmically at membrane potentials close to action potential threshold, and b) that these PNs, along with BLA interneurons (INs), are embedded in a structurally organized intrinsic neural network that facilitates synchronous activation of groups of PNs. A combination of electrophysiological and anatomical approaches will be used to test this hypothesis including: 1. Characterize and contrast the physiological and neuroanatomical properties contributing to oscillatory activity in PNs of the magnocellular and parvicellular subdivisions of the BLA. 2. Characterize the intrinsic network connectivity of the rat BLA using dual cell recording to show synchronous activity in PN-PN interactions, and PN-IN interactions. 3. Characterize the physiological properties of BLA PNs that project to the prefrontal cortex in rat and primate. By clarifying the role of intrinsic microcircuits of the BLA in generating synchronized oscillatory activity and its relationship with the PFC, these studies will be critical in furthering our understanding of affective disorders and in developing novel therapeutic treatment strategies.

描述（由申请人提供）：杏仁核在处理情感刺激中起着至关重要的作用。在人类中，成像研究表明，杏仁核和额叶皮层（PFC）之间的相互相互作用可能与情感的皮质控制有关。值得注意的是，只有杏仁核（BLA）的基底外侧核与PFC具有相互的连接，并且响应于BLA中的情感刺激激发活性，在PFC中的发射活性之前。此外，在恐惧调节期间，BLA和PFC神经元的发射活性变得同步。人们认为，神经网络中的同步振荡代表了一种“结合”机制，该机制迅速连接了空间远处的结构，我们的论点是，BLA和PFC中的同步活性提供了一种机制，可以快速评估感觉刺激的情绪价值。 在精神分裂症，自闭症，PTSD和抑郁症中已经观察到皮质同步异常。为了了解异常同步在情感障碍的病因中的作用，我们必须首先了解同步活动在BLA等领域通常如何发展。但是，对BLA投影神经元（PNS）局部集合的活性的过程知之甚少，更不用说如何在BLA和PFC之间实现相位同步了。我们将通过系统地检查有助于BLA PNS的振荡和同步活性的生理和神经解剖学底物来直接解决这一知识差距。更具体地说，我们将测试以下假设： PN组。电生理学和解剖学方法的结合将用于检验该假设，包括：1。表征和对比的是BLA的巨细胞和细胞细胞细胞细胞细胞分支的PNS振荡活性的生理和神经解剖学特性。 2。使用双细胞记录表征大鼠BLA的固有网络连接性，以显示PN-PN相互作用中的同步活动和PN-IN相互作用。 3。表征将大鼠和灵长类动物投射到前额叶皮层的BLA PN的生理特性。 通过阐明BLA的内在微电路在产生同步振荡活动及其与PFC的关系中的作用，这些研究对于进一步了解情感障碍和制定新型治疗策略至关重要。