Functional Neuroanatomy of the Basolateral Amygdala

基底外侧杏仁核的功能神经解剖学

基本信息

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
项目类别：
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

项目摘要

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关键作用。在人类中，影像学研究表明杏仁核和前额皮质（PFC）之间的相互作用可能与皮质对情感的控制有关。值得注意的是，只有杏仁核基底外侧核 (BLA) 与 PFC 具有明显的相互联系，并且 BLA 对情感刺激的放电活动先于 PFC 的放电活动。此外，在恐惧调节过程中，BLA 和 PFC 神经元的放电活动变得同步。神经网络中的同步振荡被认为代表了一种快速连接空间遥远结构的“结合”机制，我们认为 BLA 和 PFC 中的同步活动提供了一种可以快速评估感觉刺激的情绪效价的机制。在精神分裂症、自闭症、创伤后应激障碍和抑郁症中观察到皮质同步异常。为了了解异常同步性在情感障碍病因学中的作用，我们必须首先了解同步性活动在 BLA 等区域通常是如何发展的。然而，人们对 BLA 投射神经元 (PN) 局部集合活动同步的过程知之甚少，更不用说 BLA 和 PFC 之间如何实现相位同步了。我们将通过系统地检查有助于 BLA PN 振荡和同步活动的生理和神经解剖学基础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：a) 内在膜电流赋予 BLA PN 一种“共振频率”，使神经元倾向于以接近动作电位阈值的膜电位有节奏地放电，b) 这些 PN 与 BLA 一起中间神经元 (IN) 嵌入结构组织的内在神经网络中，促进 PN 组的同步激活。将使用电生理学和解剖学方法的组合来检验这一假设，包括： 1. 表征和对比 BLA 的大细胞和小细胞细分的 PN 中有助于振荡活动的生理和神经解剖学特性。 2. 使用双细胞记录表征大鼠 BLA 的内在网络连接，以显示 PN-PN 相互作用和 PN-IN 相互作用中的同步活动。 3. 表征投射到大鼠和灵长类动物前额皮质的 BLA PN 的生理特性。通过阐明 BLA 内在微电路在产生同步振荡活动中的作用及其与 PFC 的关系，这些研究对于进一步了解情感障碍和开发新的治疗策略至关重要。