Stanford I M, Lacey M G
Department of Pharmacology, The Medical School, University of Birmingham, United Kingdom.
J Neurosci. 1996 Dec 1;16(23):7566-73. doi: 10.1523/JNEUROSCI.16-23-07566.1996.
The ability of serotonin to modulate GABA-mediated synaptic input to substantia nigra pars reticulata (SNr) neurons was investigated with the use of whole-cell patch-clamp recording from slices of rat midbrain. Fast evoked GABA(A) receptor-mediated synaptic currents (IPSCs) were attenuated reversibly approximately 60% by serotonin, which also caused an inward current with reversal potential of -25 mV. This inward current was blocked by the 5-HT2 receptor antagonist ritanserin, whereas the IPSC depression was blocked by the 5-HT1B receptor antagonist pindolol. The amplitude ratio of IPSC pairs (50 msec interpulse interval) was enhanced by serotonin (in ritanserin) and also by the GABA(B) receptor agonist baclofen (which also depressed the IPSC), consistent with a presynaptic site of action in both cases. In contrast, spontaneous tetrodotoxin-sensitive GABA(A) synaptic currents (sIPSCs) were increased in frequency by serotonin (an action that was sensitive to ritanserin, but not pindolol) but reduced in frequency by baclofen. SNr neurons therefore receive inhibitory synaptic input mediated by GABA(A) receptors from at least two distinct sources. One, probably originating from the striatum, may be depressed via presynaptic 5-HT1B and GABA(B) receptors. The second is likely to arise from axon collaterals of SNr neurons themselves and is facilitated by an increase in firing via postsynaptic, somatodendritic 5-HT2C receptor activation, but it is depressed by GABA(B) receptor activation. Thus, serotonin can both depolarize and disinhibit SNr neurons via 5-HT2C and 5-HT1B receptors, respectively, but excitation may be limited by GABA released from axon collaterals.
利用大鼠中脑切片的全细胞膜片钳记录技术，研究了血清素调节黑质网状部（SNr）神经元GABA介导的突触输入的能力。快速诱发的GABA(A)受体介导的突触电流（IPSCs）被血清素可逆性衰减约60%，血清素还引起了反转电位为-25 mV的内向电流。这种内向电流被5-HT2受体拮抗剂利坦色林阻断，而IPSC的抑制被5-HT1B受体拮抗剂吲哚洛尔阻断。血清素（在利坦色林存在的情况下）以及GABA(B)受体激动剂巴氯芬（它也抑制IPSC）均可增强IPSC对（脉冲间隔50毫秒）的幅度比，这与两种情况下的突触前作用位点一致。相比之下，血清素可增加自发性河豚毒素敏感的GABA(A)突触电流（sIPSCs）的频率（该作用对利坦色林敏感，但对吲哚洛尔不敏感），而巴氯芬则降低其频率。因此，SNr神经元接受至少两个不同来源的由GABA(A)受体介导的抑制性突触输入。一个可能起源于纹状体，可能通过突触前5-HT1B和GABA(B)受体受到抑制。第二个可能源于SNr神经元自身的轴突侧支，通过突触后树突体5-HT2C受体激活增加放电而促进，但被GABA(B)受体激活所抑制。因此，血清素可分别通过5-HT2C和5-HT1B受体使SNr神经元去极化和解除抑制，但兴奋可能受到轴突侧支释放的GABA的限制。
