A neonatal ventral hippocampal lesion causes functional deficits in adult prefrontal cortical interneurons.
A neonatal ventral hippocampal lesion causes functional deficits in adult prefrontal cortical interneurons.
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DOI：
10.1523/jneurosci.4166-08.2008
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发表时间：
2008-11-26
期刊：
影响因子：
--
通讯作者：
O'Donnell P
中科院分区：
文献类型：
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作者：
Tseng KY;Lewis BL;Hashimoto T;Sesack SR;Kloc M;Lewis DA;O'Donnell P
患有新生儿海马腹侧病变（NVHL）的动物在青春期或青春期后会出现异常行为，这表明早期的损伤可能会产生延迟的后果。许多这些行为依赖于前额叶皮质（PFC），我们已经报道过NVHL成年大鼠的PFC锥体神经元对腹侧被盖区（VTA）刺激的反应是放电增加而不是特征减少。由于多巴胺（DA）调节皮层中间神经元在青春期成熟，这些发现提出了NVHL大鼠PFC内局部抑制回路成熟可能已经改变的可能性。在这里，我们通过钙结合蛋白小白蛋白（PV）和GABA合成酶GAD67 mrna的原位杂交测量以及中间神经元功能的电生理测量来评估NVHL大鼠PFC中间神经元的状态。虽然PV和GAD67没有差异，但切片的全细胞记录显示NVHL大鼠中间神经元对D2激动剂喹匹罗的异常反应。在NVHL大鼠的切片中，D2对局部抑制的调节的丧失也很明显，因为锥体神经元兴奋性突触反应的D2衰减中缺乏持久的成分，而假药大鼠的D2衰减是微毒素敏感的。结果表明，新生儿病变导致青春期PFC中间神经元发育不成熟，而不是丧失，这一发现与目前对精神分裂症成像数据的解释一致，表明PFC和其他皮质区域存在过度活跃、“嘈杂”的皮层功能障碍。
Animals with a neonatal ventral hippocampal lesion (NVHL) develop abnormal behaviors during or after adolescence, suggesting that early insults can have delayed consequences. Many of these behaviors depend on the prefrontal cortex (PFC), and we have reported that PFC pyramidal neurons of adult rats with a NVHL respond to stimulation of the ventral tegmental area (VTA) with an increase in firing instead of the characteristic decrease. As the dopamine (DA) modulation of cortical interneurons matures during adolescence, these findings raise the possibility that maturation of local inhibitory circuits within the PFC may have been altered in NVHL rats. Here, we assessed the state of PFC interneurons in NVHL rats with in situ hybridization measures of the mRNAs for the calcium binding protein parvalbumin (PV) and the GABA synthesizing enzyme GAD67, as well as with electrophysiological measures of interneuron function. Although no differences were observed with PV or GAD67, whole-cell recordings in slices revealed abnormal responses to the D2 agonist quinpirole in interneurons from NVHL rats. The loss of D2 modulation of local inhibition in slices from NVHL rats was also evident in the absence of a lasting component in the D2 attenuation of excitatory synaptic responses in pyramidal neurons, which in sham treated rats was picrotoxin-sensitive. The results suggest that the neonatal lesion causes improper maturation, but not loss, of PFC interneurons during adolescence, a finding consistent with current interpretations of imaging data in schizophrenia that suggest a hyperactive, “noisy” cortex underlying dysfunction in the PFC and other cortical areas.