Changes in hippocampal circuitry after pilocarpine-induced seizures as revealed by opioid receptor distribution and activation
Changes in hippocampal circuitry after pilocarpine-induced seizures as revealed by opioid receptor distribution and activation
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DOI：
10.1523/jneurosci.17-01-00477.1997
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发表时间：
1997-01-01
影响因子：
5.3
通讯作者：
Chavkin, C
中科院分区：
文献类型：
--
作者：
Bausch, SB;Chavkin, C
采用匹罗卡品颞叶癫痫模型研究癫痫发作后齿状回电路的时间依赖性变化。癫痫发作导致大鼠门部的mu-和delta-阿片受体免疫反应神经元（分别为DOR-IR和DOR-IR）和颗粒细胞层的mr - ir神经元减少。此外，弥漫性DOR-IR、DOR-IR和GABA免疫反应（GABA- ir）在内分子层均升高。通过体外海马切片制备研究解剖变化的生理后果，我们发现，注射匹罗卡平后5-13 d， mu-阿片受体激动剂[d - ala (2),MePhe(4),Gly-(ol)(5)]-脑啡肽（DAMGO）和GABA(A)受体拮抗剂bicuculline的去抑制作用明显下降，但在6周内恢复到对照水平。注射匹罗卡品后5 ~ 13 d，单突触诱导的IPSCs的振幅和DAMGO对该参数的影响也略有下降，但在6周时显著升高。在注射匹罗卡平6周后，DAMGO显著降低了自发IPSCs （sIPSCs）的平均振幅，但在对照组中没有。δ -阿片受体激动剂[D-Pen(2,5)]-脑啡肽（DPDPE）主要抑制盐处理动物的兴奋性传递，既不影响sIPSCs，也不诱发IPSCs。dpdpe诱导的兴奋性传递抑制在注射匹罗卡品后6周更加明显。这些结果说明了颞叶癫痫动物模型中齿状回回路的解剖重组和功能改变，并为海马结构损伤后代偿性改变提供了证据。
The pilocarpine model of temporal robe epilepsy was used to study the time-dependent changes in dentate gyrus circuitry after seizures. Seizures caused a decrease in mu- and delta-opioid receptor immunoreactive (MOR-IR and DOR-IR, respectively) neurons in the hilus and MOR-IR neurons in the granule cell layer. Additionally, diffuse DOR-IR, MOR-IR, and GABA immunoreactivities (GABA-IR) were increased in the inner molecular layer. Using the in vitro hippocampal slice preparation to study the physiological consequences of the anatomical changes, we found that the disinhibitory effects of the mu-opioid receptor agonist [D-Ala(2),MePhe(4),Gly-(ol)(5)]-enkephalin (DAMGO) and the GABA(A) receptor antagonist bicuculline were greatly depressed 5-13 d after pilocarpine injection but returned to control levels within 6 weeks. The amplitudes of monosynaptic evoked IPSCs and the effects of DAMGO on this parameter were also slightly decreased 5-13 d after pilocarpine injection but significantly increased at 6 weeks. DAMGO significantly decreased the mean amplitude of spontaneous IPSCs (sIPSCs) at 6 weeks after pilocarpine injection but not in controls. The delta-opioid receptor agonist [D-Pen(2,5)]-enkephalin (DPDPE) principally inhibited excitatory transmission in saline-treated animals without affecting either sIPSCs or evoked IPSCs. The DPDPE-induced inhibition of excitatory transmission became more pronounced at 6 weeks after pilocarpine injection. These results illustrate the anatomical reorganization and functional changes in dentate gyrus circuitry evident in an animal model of temporal lobe epilepsy and provide evidence of compensatory changes after trauma to the hippocampal formation.