Prenatal disruption of neocortical development alters prefrontal cortical neuron responses to dopamine in adult rats
Prenatal disruption of neocortical development alters prefrontal cortical neuron responses to dopamine in adult rats
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DOI：
10.1038/sj.npp.1300696
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发表时间：
2005-08-01
影响因子：
7.6
通讯作者：
Grace, AA
中科院分区：
文献类型：
--
作者：
Lavin, A;Moore, HM;Grace, AA
越来越多的证据表明，大脑皮层的结构变化可能会破坏涉及前额叶皮层（PFC）的多巴胺能神经元的传递，并可能导致精神分裂症的病因。在这项研究中，我们利用啮齿动物模型的新生儿皮质发育中断使用产前管理的丝裂毒素甲基偶氮甲醇乙酸酯（MAM）。使用细胞内记录在体内，我们比较了生理学的前额叶皮层神经元和他们的反应，局部给药多巴胺（DA）在完整的动物和成年大鼠产前处理MAM。局部给药DA超极化膜电位（MP），并降低记录在完整的动物PFC深层的神经元的放电率。此外，电刺激腹侧被盖区诱发快发作epsps或持久的PFC神经元的去极化。相比之下，在MAM处理的动物中记录的PFC神经元具有显著更快的基线放电速率。此外，局部施用DA并不影响MAM处理的动物中的神经元的MP或放电率。然而，MAM处理的动物表现出增加的神经元的百分比与持久的去极化刺激的腹侧被盖区。这项研究的结果表明，PFC神经元在MAM处理的大鼠是没有反应的DA管理的表面，而在同一时间表现出更大的响应VTA刺激。这些结果与皮质边缘系统对神经发育损伤的反应是一致的。
A growing body of evidence suggests that structural changes in the cortex may disrupt dopaminergic transmission in circuits involving the prefrontal cortex (PFC) and may contribute to the etiology of schizophrenia. In this study, we utilize a rodent model of neonatal disruption of cortical development using prenatal administration of the mitotoxin methylazoxymethanol acetate (MAM). Using intracellular recordings in vivo, we compare the physiology of prefrontal cortical neurons and their responses to topical administration of dopamine (DA) in intact animals and adult rats treated prenatally with MAM. Topical administration of DA hyperpolarized the membrane potential (MP) and decreased the firing rate of neurons recorded in deep layers of the PFC in intact animals. Furthermore, electrical stimulation of the VTA evoked fast onset epsps or long-lasting depolarizations in PFC neurons. In comparison, PFC neurons recorded in MAM-treated animals had significantly faster baseline firing rates. Moreover, topical administration of DA did not affect the MP or firing rate of the neurons in MAM-treated animals. However, MAM-treated animals exhibited an increase in the percentage of neurons responding with long-lasting depolarizations to stimulation of the VTA. The results of this study indicate that PFC neurons in the MAM-treated rats are not responsive to DA administered superficially, while at the same time exhibit greater responsiveness to VTA stimulation. These results are consistent with a rewiring of the corticolimbic system in response to neurodevelopmental insults.