Van Bockstaele E J, Sesack S R, Pickel V M
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021.
J Comp Neurol. 1994 Mar 1;341(1):1-15. doi: 10.1002/cne.903410102.
Dynorphin facilitates conditioned place aversion and reduces locomotor activity through mechanisms potentially involving direct activation of target neurons or release of catecholamines from afferents in the nucleus accumbens. We examined the ultrastructural substrates underlying these actions by combining immunoperoxidase labeling for dynorphin 1-8 and immunogold silver labeling for the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH). The two markers were simultaneously visualized in single coronal sections through the rat nucleus accumbens. By light microscopy, dynorphin immunoreactivity was seen as patches of immunoreactive varicosities throughout all rostrocaudal levels of the nucleus accumbens. The dynorphin-immunoreactive terminals identified by electron microscopy ranged from 0.2 to 1.5 microns in cross-sectional diameter, contained numerous small (30-40 nm) clear vesicles, as well as one or more large (80-100 nm) dense core vesicles. From the dynorphin-immunoreactive terminals quantitatively examined in single sections, 74% (173/370) showed symmetric synaptic junctions mainly with large unlabeled dendrites. Of the dynorphin-immunoreactive terminals forming identifiable synapses, approximately 30% contacted more than one dendritic target. In addition, single dendrites frequently received convergent input from more than one dynorphin-labeled terminal. Irrespective of their dendritic associations, dynorphin-immunoreactive terminals also frequently showed close appositions with other axons and terminals; these included unlabeled (41%), TH-labeled (10%) or dynorphin-labeled axons (14%). In contrast to dynorphin-immunoreactive terminals, TH-labeled terminals formed primarily symmetric synapses with small dendrites and spines or lacked recognizable specializations in the plane of section analyzed. In some cases, single dendrites were postsynaptic to both dynorphin and TH-immunoreactive terminals. We conclude that dynorphin-immunoreactive terminals potently modulate, and most likely inhibit, target neurons in both subregions of the rat nucleus accumbens. This modulatory action could attenuate or potentiate incoming catecholamine signals on more distal dendrites of the accumbens neurons. The findings also suggest potential sites for presynaptic modulatory interactions involving dynorphin and catecholamine or other transmitters in apposed terminals.
强啡肽通过可能涉及直接激活靶神经元或从伏隔核传入纤维释放儿茶酚胺的机制，促进条件性位置厌恶并降低运动活性。我们通过结合强啡肽1 - 8的免疫过氧化物酶标记和儿茶酚胺合成酶酪氨酸羟化酶（TH）的免疫金银标记，研究了这些作用背后的超微结构基础。在穿过大鼠伏隔核的单个冠状切片中同时观察到这两种标记物。通过光学显微镜，在伏隔核的所有 rostrocaudal 水平上，强啡肽免疫反应性表现为免疫反应性曲张体的斑块。通过电子显微镜鉴定的强啡肽免疫反应性终末，其横截面直径在0.2至1.5微米之间，含有许多小的（30 - 40纳米）清亮小泡，以及一个或多个大的（80 - 100纳米）致密核心小泡。在单切片中定量检查的强啡肽免疫反应性终末中，74%（173/370）显示主要与大的未标记树突形成对称突触连接。在形成可识别突触的强啡肽免疫反应性终末中，约30%与不止一个树突靶点接触。此外，单个树突经常从不止一个强啡肽标记的终末接收汇聚输入。无论其与树突的关联如何，强啡肽免疫反应性终末也经常与其他轴突和终末紧密并置；这些包括未标记的（41%）、TH标记的（10%）或强啡肽标记的轴突（14%）。与强啡肽免疫反应性终末不同，TH标记的终末主要与小树突和棘形成对称突触，或者在所分析的切片平面中缺乏可识别的特化结构。在某些情况下，单个树突对强啡肽和TH免疫反应性终末均为突触后。我们得出结论，强啡肽免疫反应性终末有力地调节并极有可能抑制大鼠伏隔核两个亚区域中的靶神经元。这种调节作用可能会减弱或增强伏隔核神经元更远端树突上传入的儿茶酚胺信号。这些发现还提示了在并置终末中涉及强啡肽和儿茶酚胺或其他递质的突触前调节相互作用的潜在位点。
