Bausch S B, Chavkin C
Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA.
J Neurosci. 1997 Jan 1;17(1):477-92. doi: 10.1523/JNEUROSCI.17-01-00477.1997.
The pilocarpine model of temporal lobe 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-Ala2, MePhe4,Gly-(ol)5]-enkephalin (DAMGO) and the GABAA 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-Pen2,5]-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.
采用毛果芸香碱颞叶癫痫模型研究癫痫发作后齿状回神经回路随时间的变化。癫痫发作导致齿状回门区中μ-阿片受体免疫反应性（MOR-IR）神经元和δ-阿片受体免疫反应性（DOR-IR）神经元数量减少，以及颗粒细胞层中MOR-IR神经元数量减少。此外，内分子层中弥漫性的DOR-IR、MOR-IR和GABA免疫反应性（GABA-IR）增加。利用体外海马脑片制备技术研究解剖学变化的生理后果，我们发现，在注射毛果芸香碱后5-13天，μ-阿片受体激动剂[D-Ala2，MePhe4，Gly-(ol)5]-脑啡肽（DAMGO）和GABAA受体拮抗剂荷包牡丹碱的去抑制作用大幅降低，但在6周内恢复到对照水平。在注射毛果芸香碱后5-13天，单突触诱发IPSCs的幅度以及DAMGO对该参数的影响也略有降低，但在6周时显著增加。在注射毛果芸香碱6周后，DAMGO显著降低了自发性IPSCs（sIPSCs）的平均幅度，但在对照组中未出现此现象。δ-阿片受体激动剂[D-Pen2，5]-脑啡肽（DPDPE）主要抑制生理盐水处理动物的兴奋性传递，而不影响sIPSCs或诱发的IPSCs。在注射毛果芸香碱6周后，DPDPE诱导的兴奋性传递抑制作用变得更加明显。这些结果说明了在颞叶癫痫动物模型中齿状回神经回路明显的解剖学重组和功能变化，并为海马结构损伤后的代偿性变化提供了证据。
