Aston-Jones G, Shipley M T, Chouvet G, Ennis M, van Bockstaele E, Pieribone V, Shiekhattar R, Akaoka H, Drolet G, Astier B
Department of Mental Health Sciences, Hahnemann University, Philadelphia, PA.
Prog Brain Res. 1991;88:47-75. doi: 10.1016/s0079-6123(08)63799-1.
Tract-tracing and electrophysiology studies have revealed that major inputs to the nucleus locus coeruleus (LC) are found in two structures, the nucleus paragigantocellularis (PGi) and the perifascicular area of the nucleus prepositus hypoglossi (PrH), both located in the rostral medulla. Minor afferents to LC were found in the dorsal cap of the paraventricular hypothalamus and spinal lamina X. Recent studies have also revealed limited inputs from two areas nearby the LC, the caudal midbrain periaqueductal gray (PAG) and the ventromedial pericoerulear region. The pericoeruleus may provide a local circuit interface to LC neurons. Recent electron microscopic analyses have revealed that LC dendrites extend preferentially into the rostromedial and caudal juxtaependymal pericoerulear regions. These extracoerulear LC dendrites may receive afferents in addition to those projecting to LC proper. However, single-pulse stimulation of inputs to such dendritic regions reveals little or no effect on LC neurons. Double-labeling studies have revealed that a variety of neurotransmitters impinging on LC neurons originate in its two major afferents, PGi and PrH. The LC is innervated by PGi neurons that stain for markers of adrenalin, enkephalin or corticotropin-releasing factor. Within PrH, large proportions of LC-projecting neurons stained for GABA or met-enkephalin. Finally, in contrast to previous conclusions, the dorsal raphe does not provide the robust 5-HT innervation found in the LC. We conclude that 5-HT inputs may derive from local 5-HT neurons in the pericoerulear area. Neuropharmacology experiments revealed that the PGi provides a potent excitatory amino acid (EAA) input to the LC, acting primarily at non-NMDA receptors in the LC. Other studies indicated that this pathway mediates certain sensory responses of LC neurons. NMDA-mediated sensory responses were also revealed during local infusion of magnesium-free solutions. Finally, adrenergic inhibition of LC from PGi could also be detected in nearly every LC neuron tested when the EAA-mediated excitation is first eliminated. In contrast to PGi, the PrH potently and consistently inhibited LC neurons via a GABAergic projection acting at GABAA receptors within LC. Such PrH stimulation also potently attenuated LC sensory responses. Finally, afferents to PGi areas that also contain LC-projecting neurons were identified. Major inputs were primarily autonomic in nature, and included the caudal medullary reticular formation, the parabrachial and Kölliker-Fuse nuclei, the PAG, NTS and certain hypothalamic areas.(ABSTRACT TRUNCATED AT 400 WORDS)
神经束追踪和电生理学研究表明，蓝斑核（LC）的主要输入来自位于延髓头端的两个结构，即巨细胞旁核（PGi）和舌下前置核（PrH）的束周区。LC的次要传入纤维见于下丘脑室旁核背帽和脊髓板层X。最近的研究还发现，LC附近的两个区域，即尾侧中脑导水管周围灰质（PAG）和蓝斑周腹内侧区，也有有限的输入。蓝斑周区可能为LC神经元提供局部回路接口。最近的电子显微镜分析显示，LC的树突优先延伸至头内侧和尾侧室管膜旁蓝斑周区。这些蓝斑外的LC树突除了接受投射到LC本体的传入纤维外，可能还接受其他传入纤维。然而，对这些树突区域的输入进行单脉冲刺激，对LC神经元几乎没有影响或没有影响。双标记研究表明，作用于LC神经元的多种神经递质起源于其两个主要传入纤维，即PGi和PrH。LC由PGi神经元支配，这些神经元可被肾上腺素、脑啡肽或促肾上腺皮质激素释放因子的标记物染色。在PrH内，大部分投射到LC的神经元可被GABA或甲硫脑啡肽染色。最后，与之前的结论相反，中缝背核并不像在LC中那样提供强大的5-羟色胺（5-HT）神经支配。我们得出结论，5-HT输入可能来自蓝斑周区的局部5-HT神经元。神经药理学实验表明，PGi向LC提供强大的兴奋性氨基酸（EAA）输入，主要作用于LC中的非NMDA受体。其他研究表明，该通路介导LC神经元的某些感觉反应。在局部注入无镁溶液时，也可观察到NMDA介导的感觉反应。最后，当首先消除EAA介导的兴奋时，在几乎每个测试的LC神经元中都能检测到PGi对LC的肾上腺素能抑制作用。与PGi相反，PrH通过作用于LC内GABAA受体的GABA能投射，有力且持续地抑制LC神经元。这种PrH刺激也能有力地减弱LC的感觉反应。最后，确定了也包含投射到LC的神经元的PGi区域的传入纤维。主要输入主要是自主性的，包括延髓尾侧网状结构、臂旁核和 Kölliker-Fuse核、PAG、孤束核和某些下丘脑区域。（摘要截断于400字）
