Van Bockstaele E J, Bajic D, Proudfit H, Valentino R J
Department of Pathology, Anatomy and Cell Biology, Suite 520, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Physiol Behav. 2001 Jun;73(3):273-83. doi: 10.1016/s0031-9384(01)00448-6.
Peripheral sympathetic nerves and brainstem noradrenergic neurons of the locus coeruleus (LC) respond in parallel to a variety of stress-related stimuli which results in norepinephrine release both peripherally and centrally. Elucidation of central pathways subserving modulation of LC neurons point to extranuclear noradrenergic dendrites of LC somata that extend into peri-coerulear areas as a major target of afferents that participate in behavioral and physiological responses to stress. Anterograde tract tracing combined with immunoelectron microscopic detection of the catecholamine synthesizing enzyme tyrosine hydroxylase (TH) has demonstrated that the nucleus of the solitary tract (NTS) and the ventrolateral aspect of the periaqueductal gray (PAG), regions that participate in coordinating autonomic and motor behavior in response to stress, preferentially target the rostral ventromedial aspect of the peri-LC. In contrast, limbic forebrain afferents including the central nucleus of the amygdala (CNA) and the bed nucleus of the stria terminalis (BNST), regions that coordinate emotional responses to external stressors, provide direct synaptic input to noradrenergic dendrites that extend into rostral dorsolateral peri-coerulear areas. Neurochemical identification of transmitter systems impinging on LC indicate that the CNA provides corticotropin-releasing factor (CRF), a peptide essential for integrated physiological responses to stress, to the dorsolateral LC. Endogenous opioid peptides that originate from medullary sources, however, target primarily the "core" of the LC. Our physiological data suggest that stress engages CRF and opioid afferents to the LC, which have opposing influences on this noradrenergic system. The balance between opioid and CRF influences acting in the LC may, in part, maintain the balance of active and passive coping behaviors in response to stress. Understanding the afferent and neurochemical organization of the LC may help elucidate adaptations in neural circuits associated with stress which impact on central noradrenergic function.
外周交感神经和蓝斑（LC）的脑干去甲肾上腺素能神经元对多种与应激相关的刺激产生平行反应，这导致外周和中枢都释放去甲肾上腺素。对介导LC神经元调节的中枢通路的阐明表明，LC胞体的核外去甲肾上腺素能树突延伸到蓝斑周围区域，是参与对应激的行为和生理反应的传入神经的主要靶点。顺行束路追踪结合对儿茶酚胺合成酶酪氨酸羟化酶（TH）的免疫电子显微镜检测表明，孤束核（NTS）和导水管周围灰质（PAG）的腹外侧部分，这些参与协调对应激的自主和运动行为的区域，优先靶向LC周围区域的吻侧腹内侧部分。相比之下，包括杏仁核中央核（CNA）和终纹床核（BNST）在内的边缘前脑传入神经，这些协调对外部应激源的情绪反应的区域，为延伸到吻侧背外侧蓝斑周围区域的去甲肾上腺素能树突提供直接的突触输入。对作用于LC的递质系统的神经化学鉴定表明，CNA向背外侧LC提供促肾上腺皮质激素释放因子（CRF），这是一种对应激综合生理反应必不可少的肽。然而，源自髓质的内源性阿片肽主要靶向LC的“核心”。我们的生理学数据表明，应激使CRF和阿片类传入神经作用于LC，它们对这个去甲肾上腺素能系统有相反的影响。阿片类和CRF在LC中的作用之间的平衡可能部分维持了对应激的主动和被动应对行为之间的平衡。了解LC的传入神经和神经化学组织可能有助于阐明与应激相关的神经回路中的适应性变化，这些变化会影响中枢去甲肾上腺素能功能。
