Serotonergic modulation of GABAergic and glutamatergic synaptic transmission in mechanically isolated rat medial preoptic area neurons
Serotonergic modulation of GABAergic and glutamatergic synaptic transmission in mechanically isolated rat medial preoptic area neurons
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DOI：
10.1038/sj.npp.1301396
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发表时间：
2008-01-01
影响因子：
7.6
通讯作者：
Cho, Young-Wuk
中科院分区：
文献类型：
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作者：
Lee, Jong-Ju;Hahm, Eu-Teum;Cho, Young-Wuk
下丘脑内侧视前区（MPOA）在男性性行为的调节中起着重要作用，并参与了一些稳态过程。血清素（5-羟色胺，5-HT）通过在MPOA中的作用抑制性行为，其中存在高密度的5-HT 1A和5-HT 1B受体亚型。我们使用电压钳条件下的全细胞记录，以探讨γ-氨基丁酸（GABA）能和多巴胺能突触传递在机械分离的大鼠MPOA神经元与本机突触前神经末梢的多巴胺能调制。荷包牡丹碱可完全阻断MPOA自发GABA能微型抑制性突触后电流（mIPSCs）。血清素可逆地降低GABA能mIPSC频率，而不影响平均电流幅度。5-HT 1A受体特异性激动剂（+/-）-8-羟基-2-二丙氨基四氢萘氢溴酸盐模拟5-羟色胺能抑制mIPSC频率，并被特异性5-HT 1A受体拮抗剂1-（2-甲氧基苯基）-4-[4-（2-邻苯二甲酰亚胺基）-丁基]哌嗪氢溴酸盐阻断。6-氰基-7-硝基喹喔啉-2，3-二酮可完全阻断MPOA中自发性突触能微小兴奋性突触后电流（mEPSC）。5-羟色胺可逆性地降低了海马能mEPSC频率，而不影响平均电流幅度。5-HT 1B受体激动剂CGS 12066 B可模拟5-HT 1B受体对mEPSC频率的抑制作用，5-HT 1B受体拮抗剂SB 216641可阻断5-HT 1B受体对mEPSC频率的抑制作用。用forskolin刺激腺苷酸环化酶可增加GABA能mIPSC和谷氨酸能mEPSC的频率，并阻断5-HT的抑制作用。选择性蛋白激酶A（PKA）抑制剂H-89可降低GABA能mIPSC和谷氨酸能mEPSC的频率，并阻断5-HT对它们的抑制作用。这些结果表明，5-HT通过5-HT 1A和5-HT 1B受体介导的抑制MPOA神经元突触前神经末梢中的PKA依赖性通路，降低GABA能mIPSC和多巴胺能mEPSC的频率。
The medial preoptic area (MPOA) of the hypothalamus is critically involved in the regulation of male sexual behavior and has been implicated in several homeostatic processes. Serotonin (5-hydroxytryptamine, 5-HT) inhibits sexual behavior via effects in the MPOA, where there are high densities of 5-HT1A and 5-HT1B receptor subtypes. We used whole-cell recordings under voltage-clamp conditions to investigate the serotonergic modulation of gamma-aminobutyric acid (GABA)ergic and glutamatergic synaptic transmission in mechanically dissociated rat MPOA neurons with native presynaptic nerve endings. Spontaneous GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in the MPOA were completely blocked by bicuculline. Serotonin reversibly reduced the GABAergic mIPSC frequency without affecting the mean current amplitude. Serotonergic inhibition of mIPSC frequency was mimicked by (+/-)-8-hydroxy-2-dipropylaminotetralin hydrobromide, a specific 5-HT1A receptor agonist, and blocked by 1-(2- methoxyphenyl)-4-[4-(2-phthalimido)-butyl] piperazine hydrobromide, a specific 5-HT1A receptor antagonist. 6-Cyano-7-nitroquinoxaline-2,3-dione completely blocked spontaneous glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in the MPOA. Serotonin reversibly decreased the glutamatergic mEPSC frequency without affecting the mean current amplitude. Serotonergic inhibition of mEPSC frequency was mimicked by CGS 12066B, a specific 5-HT1B receptor agonist, and blocked by SB 216641, a specific 5-HT1B receptor antagonist. Stimulation of adenylyl cyclase with forskolin increased the frequencies of GABAergic mIPSCs and glutamatergic mEPSCs, and blocked the inhibitory effects of 5-HT. H-89, a selective protein kinase A (PKA) inhibitor, decreased the frequencies of GABAergic mIPSCs and glutamatergic mEPSCs, and blocked their reduction by 5-HT. These findings suggest that 5-HT reduces the frequency of GABAergic mIPSCs and glutamatergic mEPSCs through 5-HT1A and 5-HT1B receptor-mediated inhibition, respectively, of the PKA-dependent pathway in the presynaptic nerve terminals of MPOA neurons.