Pereda A, Triller A, Korn H, Faber D S
Division of Neurobiology, State University of New York, Buffalo 14214.
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12088-92. doi: 10.1073/pnas.89.24.12088.
The transmitter dopamine reduces electrotonic coupling between retinal horizontal cells and increases their sensitivity to glutamate. Since in other systems single afferents establish mixed electrotonic and chemical excitatory synapses with their targets, dopamine might be expected there to depress one component of excitation while enhancing the other. This hypothesis was tested by applying dopamine locally in the vicinity of the lateral dendrite of the goldfish Mauthner cell (M cell) and monitoring the composite electrotonic and chemical excitatory postsynaptic potentials and currents evoked by ipsilateral eighth nerve stimulation. Dopamine produces persistent enhancements of both components of the postsynaptic response while it also increases input conductance. All these dopamine actions are prevented by superfusing the brain with saline containing the dopamine D1 receptor antagonist SCH-23390. Postsynaptic injections of the cAMP-dependent protein kinase inhibitor (Walsh inhibitor, or PKI5-24) block the dopamine-induced changes in synaptic transmission, implicating a cAMP-dependent mechanism. Furthermore, there is a dopaminergic innervation of the M cell, as demonstrated immunohistochemically with antibodies against dopamine and the rate-limiting enzyme in its synthetic pathway, tyrosine hydroxylase. Varicose immunoreactive fibers lie in the vicinity of the distal part of the lateral dendrite between the large myelinated club endings that establish the mixed synapses. As determined with electron microscopy, the dopaminergic fibers contain small vesicles, and they do not have synaptic contacts with either the afferents or the M cell, remaining instead in the synaptic bed. Taken together, these results suggest that dopamine released at a distance from these terminals increases the gain of this primary sensory input to the M cell, most likely through a phosphorylation mechanism.
神经递质多巴胺可减少视网膜水平细胞之间的电紧张性耦合，并提高它们对谷氨酸的敏感性。由于在其他系统中，单个传入神经与其靶细胞建立了混合的电紧张性和化学性兴奋性突触，因此可以预期多巴胺在那里会抑制一种兴奋成分，同时增强另一种兴奋成分。通过在金鱼Mauthner细胞（M细胞）外侧树突附近局部应用多巴胺，并监测同侧第八神经刺激诱发的复合电紧张性和化学性兴奋性突触后电位及电流，对这一假说进行了验证。多巴胺使突触后反应的两种成分持续增强，同时还增加了输入电导。用含有多巴胺D1受体拮抗剂SCH-23390的生理盐水灌注脑可阻止多巴胺的所有这些作用。突触后注射cAMP依赖性蛋白激酶抑制剂（沃尔什抑制剂或PKI5-24）可阻断多巴胺诱导的突触传递变化，这表明存在一种cAMP依赖性机制。此外，用抗多巴胺及其合成途径中的限速酶酪氨酸羟化酶的抗体进行免疫组织化学检测表明，M细胞存在多巴胺能神经支配。曲张的免疫反应性纤维位于外侧树突远端附近，在形成混合突触的大的有髓鞘终末之间。通过电子显微镜观察确定，多巴胺能纤维含有小泡，它们与传入神经或M细胞均无突触联系，而是留在突触床中。综上所述，这些结果表明，从这些终末远处释放的多巴胺增加了对M细胞的这种初级感觉输入的增益，最有可能是通过磷酸化机制实现的。
