Acute clozapine suppresses synchronized pyramidal synaptic network activity by increasing inhibition in the ferret prefrontal cortex
Acute clozapine suppresses synchronized pyramidal synaptic network activity by increasing inhibition in the ferret prefrontal cortex
复制标题
DOI：
10.1152/jn.00400.2006
复制
发表时间：
2007-02-01
影响因子：
2.5
通讯作者：
Gao, Wen-Jun
中科院分区：
文献类型：
--
作者：
Gao, Wen-Jun
最近的研究表明，前额叶皮质神经回路受损是精神分裂症神经病理的一个显著特征。氯氮平是治疗这种衰弱疾病最有效的抗精神病药物之一。尽管氯氮平有效，但其作用于前额叶皮质回路的机制仍然知之甚少。在这项研究中，在雪貂的前额叶皮质切片上进行了多个体外全细胞记录。氯氮平有效地抑制了前额神经元自发的同步化网络活动，其抑制作用是通过减少锥体神经元之间的反复兴奋和通过可能的网络机制增强对锥体细胞的抑制输入而实现的。事实上，在去抑制的条件下，抑制效应被逆转，而氯氮平增强了重复的兴奋。这些结果表明，氯氮平缓解精神分裂症阳性症状的作用至少部分是通过调整前额叶皮质回路兴奋和抑制之间的突触平衡来实现的。
Recent studies have indicated that impaired neural circuitry in the prefrontal cortex is a prominent feature of the neuropathology of schizophrenia. Clozapine is one of the most effective antipsychotic drugs used for this debilitating disease. Despite its effectiveness, the mechanism by which clozapine acts on prefrontal cortical circuitry remains poorly understood. In this study, in vitro multiple whole cell recordings were performed in slices of the ferret prefrontal cortex. Clozapine, which effectively inhibited the spontaneous synchronized network activities in the prefrontal neurons, achieved the suppressive effect by decreasing the recurrent excitation among pyramidal neurons and by enhancing the inhibitory inputs onto pyramidal cells through a likely network mechanism. Indeed, under the condition of disinhibition, the depressing effects were reversed and clozapine enhanced the recurrent excitation. These results suggest that the therapeutic actions of clozapine in alleviating the positive symptoms of schizophrenia are achieved, at least partially, through the readjustment of synaptic balance between the excitation and inhibition in the prefrontal cortical circuitry.