The firing activity of pyramidal neurons in medial prefrontal cortex and their response to 5-hydroxytryptamine-1A receptor stimulation in a rat model of Parkinson's disease
The firing activity of pyramidal neurons in medial prefrontal cortex and their response to 5-hydroxytryptamine-1A receptor stimulation in a rat model of Parkinson's disease
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DOI：
10.1016/j.neuroscience.2009.04.069
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发表时间：
2009-09
期刊：
影响因子：
3.3
通讯作者：
Shuang Wang;Q. Zhang;Jian Liu;Zhongheng Wu;U. Ali;Yong Wang;Li Chen;Z. Gui
中科院分区：
文献类型：
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作者：
Shuang Wang;Q. Zhang;Jian Liu;Zhongheng Wu;U. Ali;Yong Wang;Li Chen;Z. Gui
本实验观察了大鼠内侧前额叶皮质锥体神经元放电频率和放电模式的变化以及选择性5-羟色胺-1A受体激动剂(R)-(+)-8-羟基-2-(二丙氨基)四氢溴酸四氢呋喃(8-OH-DPAT)和拮抗剂N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridylcyclohexane羧胺马来酸盐(WAY-100635)对神经元放电活动的影响。损毁黑质后，大鼠锥体神经元的放电频率明显增加，神经元的放电模式也发生了明显的变化，表现为更多的突发性放电。全身注射8-OH-DPAT(0.5~128μg/kg)对假手术大鼠大脑中脑前叶锥体神经元的放电有兴奋抑制作用。低剂量(0.5~32μg/kg)可引起神经元兴奋，高剂量(12 8μg/kg)可抑制神经元活动。与假手术组相比，相同剂量的8-OH-DPAT对损毁大鼠的兴奋作用不明显，但8-OH-DPAT对mPFC锥体神经元放电的抑制期仍存在。此外，mPFC内局部应用8-OH-DPAT，5μg可抑制假损毁大鼠锥体神经元的放电频率，但对损毁大鼠的放电频率无影响。8-OH-DPAT的兴奋或抑制作用可被Way-100635逆转，表明这些作用是由5-HT1a受体介导的。综上所述，这些结果表明，损毁黑质核团导致了mPFC锥体神经元的过度活动和对5-HT1A受体刺激的反应异常，提示mPFC可能参与了帕金森病精神障碍的病理生理学过程。
The changes in the firing rate and firing pattern of pyramidal neurons in medial prefrontal cortex (mPFC) and the effects of selective 5-hydroxytryptamine-1A(5-HT1A) receptor agonist (R)-(+)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) and antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridylcyclohexane carboxamide maleate salt (WAY-100635) on the firing activity of the neurons were studied in sham-lesioned rats and rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc). The lesion of the SNc increased the firing rate of pyramidal neurons significantly compared to sham-lesioned rats, and the firing pattern of these neurons also changed significantly towards a more burst-firing. The systemic administration of 8-OH-DPAT at doses in the range of 0.5–128 μg/kg showed an excitatory-inhibitory effect on the firing rate of pyramidal neurons in mPFC of sham-lesioned rats. At lower doses, 0.5–32 μg/kg, it evoked excitation of the neurons, and at a high dose, i.e. 128 μg/kg, inhibited the activity of the neurons. In contrast to sham-lesioned rats, 8-OH-DPAT, at the same doses, showed no excitatory effect in the lesioned rats although the inhibitory phase of the effect of 8-OH-DPAT on the firing rate of pyramidal neurons in mPFC was still present. Furthermore, the local application of 8-OH-DPAT, 5 μg, in mPFC inhibited the firing rate of pyramidal neurons in sham-lesioned rats, while having no effect on firing rate in the lesioned rats. The excitatory or inhibitory effects of 8-OH-DPAT were reversed by WAY-100635, indicating that these effects are mediated by 5-HT1Areceptor. Altogether, these results indicate that the lesion of the SNc leads to hyperactivity of pyramidal neurons in mPFC and the abnormality of response of these neurons to 5-HT1Areceptor stimulation, suggesting that mPFC may be involved in the pathophysiology of the psychiatric disturbance of Parkinson's disease.