Activation of medial prefrontal cortex by phencyclidine is mediated via a hippocampo-prefrontal pathway
Activation of medial prefrontal cortex by phencyclidine is mediated via a hippocampo-prefrontal pathway
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DOI：
10.1093/cercor/bhh168
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发表时间：
2005-05-01
期刊：
影响因子：
3.7
通讯作者：
Kayama, Y
中科院分区：
文献类型：
--
作者：
Jodo, E;Suzuki, Y;Kayama, Y
苯环己哌啶（PCP）是一种拟精神病药物，在健康人中激发精神分裂症样症状，PCP给药动物被用作精神分裂症的药理学模型。我们最近表明，PCP的系统管理大鼠产生持久的激活内侧前额叶皮层（mPFC）神经元的自发活动的增强，而直接应用PCP的mPFC神经元的放电活动几乎没有影响。这些发现表明，PCP诱导的mPFC神经元激活主要是通过来自mPFC以外区域的兴奋性输入引起的。在本研究中，我们研究了局部应用PCP腹侧海马（vHIP）对自由活动大鼠PFC神经元放电活动的影响。PCP局部灌注到vHIP中增加PFC神经元的自发放电，在灌注过程中增加自发活动。局部应用一种更具选择性的NMDA受体拮抗剂，MK 801，麻醉下的vHIP神经元增加了大多数神经元直接投射到mPFC的自发放电率，而局部应用MK 801的mPFC神经元没有诱导兴奋性反应，在任何这些神经元。目前的研究结果表明，紧张性兴奋性输入从vHIP的PFC可能会触发发展的行为异常。
Phencyclidine (PCP) is a psychotomimetic drug that elicits schizophrenia-like symptoms in healthy persons, and administration of PCP to animals is used as a pharmacological model of schizophrenia. We recently demonstrated that systemic administration of PCP to rats produces long-lasting activation of medial prefrontal cortex (mPFC) neurons with augmentation of locomotor activity, whereas direct application of PCP to mPFC neurons has little effect on their firing activity. These findings suggest that PCP-induced activation of mPFC neurons is elicited mainly via excitatory inputs from regions outside the mPFC. In the present study, we examined effects of local application of PCP to the ventral hippocampus (vHIP) on firing activity of PFC neurons in freely moving rats. PCP locally perfused into the vHIP increased spontaneous discharges of PFC neurons during perfusion with augmentation of locomotor activity. Local application of a more selective NMDA receptor antagonist, MK801, to vHIP neurons under anesthesia increased the spontaneous firing rates of most neurons directly projecting to the mPFC, whereas local application of MK801 to mPFC neurons did not induce excitatory responses in any of those neurons. The present results indicate that tonic excitatory inputs from the vHIP to the PFC may trigger development of behavioral abnormalities.