Project 1: Role of the Medial Nucleus of the Amygdala in Fear (pg 159)

项目 1：杏仁核内侧核在恐惧中的作用（第 159 页）

• 批准号: 7882643
• 负责人: Peter J Lang
• 金额: $ 20.05万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7882643
• 关键词: Agonist; Amygdaloid structure; Anti-Anxiety Agents; Area; Attention; Bilateral; Binding; Blood Pressure; Brain; Brain imaging; Buspirone; Cell Nucleus; Cells; Dextrans; Diazepam; Dose; Emotions; Extinction (Psychology); Fright; Hypothalamic structure; Infusion procedures; Intercalated Cell; Lateral; Lateral Septal Nucleus; Lesion; Measures; Medial; Mediating; Morphine; Naloxone; Neurons; Odors; Opiates; Opioid Receptor; Output; Proteins; Rattus; Reporting; Role; Structure of terminal stria nuclei of preoptic region; Testing; Time; Tracer; conditioned fear; dextran; gamma-Aminobutyric Acid; immunocytochemistry; neuropeptide Y; prevent; putamen; receptor

We have found in the fear potentiated startle test that bilateral local infusion of morphine into the medial nucleus of the amygdala (Me) completely blocks the expression of conditioned fear whereas infusion of comparable doses into the central (Ce), basolateral (Bla) or caudate-putamen had no effect. The effects of morphine infused into the Me were completely reversed by co-infusion of naloxone into the Me. Moreover, local infusion of naloxone into the Me completely prevented morphine, given systemically, from blocking fear potentiated startle. Local infusion of mu or delta selective opiate agonists had similar effects to morphine. At the present time it is not clear why local infusion of morphine into the Me so effectively blocks fear potentiated startle because we have not found that lesions of the Me block fear potentiated startle. Although the Me has been reported to project to the Ce we believe this apparent projection probably resulted from spread of the tracer into the Ce, because we have not found projections from the Me to the Ce using discrete infusion of the sensitive anterograde tracer biotinylated dextran into the Me. Instead, the Me projects heavily to anteriomedial bed nucleus of the stria terminalis (BNSTam) the posterior intermediate BNSTpi), and the ventromedial hypothalamus (VMH). Because the BNST projects heavily to the Ce, in fact most heavily to the output division of the Ce projections from the Me to the BNST and then to the Ce could well be involved in an inhibitory circuit activated by morphine binding to receptors in the Me. Alternatively, other brain areas might also participate in this putative fear- inhibition circuit. To evaluate this, we infused morphine into the Me and then analyzed the brain using immunocytochemistry for Fos protein as a marker of neuronal activation. Local infusion of morphine into the ME led to increases in Fos in the Me, ventral lateral septal nucleus and adjacent areas of the BNST, the intercalated cell mass on the border between the Ce and Bla, and the ventral subiculum. Because some of these areas have been implicated in the inhibition of fear we believe we may have tapped into a neuronal network involved in the inhibition of fear. Hence, we will determine the role of the BNST, ventral subiculum, lateral septum, ventromedial hypothalamus and intercalated cells in the anxiolytic effects of morphine given locally into the Me, as well as the anxiolytic effects of morphine, buspirone and diazepam given systemically. We wiU also evaluate the role of opiate receptors in the Me, neuropeptide Y (NPY) cells in the Bla and GABA in the Bla, as well as various brain areas identified above, in extinction and conditioned inhibition of fear potentiated startle. Finally, we will carry out brain imaging of odor-mediated fear retention, extinction, and conditioned inhibition in anesthetized rats usingfMRI in an 11 T magnet measured with blood pressure in the magnet and fear potentiated startle in later tests in unanesthetized rats.

我们在恐惧强化惊吓实验中发现，将吗啡局部注射到大鼠双侧内侧核。 杏仁核(Me)完全阻断条件性恐惧的表达，而向 中央(Ce)、基底外侧(Bla)或尾壳核无作用。给我注射吗啡的效果是 联合注射纳洛酮后完全逆转。此外，局部输注纳洛酮完全 阻止了系统注射的吗啡阻止恐惧加剧惊吓。选择性地局部输注MU或Delta 阿片激动剂的作用与吗啡相似。目前尚不清楚为什么局部注射吗啡进入大脑 我如此有效地阻止了恐惧加剧了惊吓，因为我们还没有发现损伤的我阻碍了恐惧的加强 吓了一跳。虽然民航处已向行政长官作出报告，但我们相信这项明显的预测可能是 从示踪剂扩散到CE，因为我们还没有使用离散的方法找到从ME到CE的投影 将敏感的顺行示踪剂生物素化葡聚糖注入肌内。相反，我在很大程度上投射到 终纹前内侧床核(BNSTam，后中间BNSTpi)和腹内侧核 下丘脑(VMH)。因为BNST主要投向行政长官，事实上最主要的是行政长官的产出部。 从Me到BNST再到Ce的投射很可能参与了由 吗啡与我体内的受体结合。或者，其他大脑区域也可能参与这种假定的恐惧-- 抑制电路。为了评估这一点，我们向脑部注射了吗啡，然后用 Fos蛋白作为神经元活化标志的免疫细胞化学研究局部向ME内注入吗啡导致 Me、腹侧隔外侧核及BNST邻近区域Fos表达增加，间质细胞团增多 Ce和Bla之间的边界，以及腹侧下丘。因为这些领域中的一些已经牵涉到 对恐惧的抑制我们认为我们可能已经利用了参与抑制恐惧的神经网络。因此， 我们将确定BNST、腹侧下丘脑、外侧隔、下丘脑腹内侧部和间质的作用 细胞在局部给予吗啡的抗焦虑作用，以及吗啡的抗焦虑作用中， 丁螺环酮和安定全身用药。我们还评估了阿片受体在神经肽Me中的作用。 Bla中的Y(NPY)细胞和Bla中的GABA以及上面所述的不同脑区处于消亡和 对恐惧的条件性抑制强化了惊吓。最后，我们将进行气味介导的恐惧保持的大脑成像， 用11T磁铁测量血压的fMRI研究麻醉大鼠的消退和条件性抑制 在后来对未麻醉大鼠的测试中，磁铁和恐惧增强了惊吓。