Bekenstein J W, Lothman E W
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908.
Science. 1993 Jan 1;259(5091):97-100. doi: 10.1126/science.8093417.
In humans temporal lobe epilepsy (TLE) is characterized by recurrent seizures, neuronal hyperexcitability, and selective loss of certain neuronal populations in the hippocampus. Animal models of the condition indicate that a diminution of inhibition mediated by gamma-aminobutyric acid (GABA) accounts for the altered function, and it has been hypothesized that the diminution arises because GABAergic basket interneurons are "dormant" as a result of their being disconnected from excitatory inputs. In hippocampal slices, inhibitory postsynaptic potentials (IPSPs) were elicited in CA1 pyramidal cells by activation of basket cells; responses from an animal model of TLE were compared to those from control tissue. IPSPs evoked indirectly by activation of terminals that then excited basket cells were reduced in the epileptic tissue, whereas IPSPs evoked by direct activation of basket cells, when excitatory neurotransmission was blocked, were not different from controls. These results provide support for the "dormant basket cell" hypothesis and have implications for the pathophysiology and treatment of human TLE.
在人类中,颞叶癫痫(TLE)的特征是反复发作的癫痫、神经元过度兴奋以及海马体中某些神经元群体的选择性丧失。该病症的动物模型表明,由γ-氨基丁酸(GABA)介导的抑制作用减弱导致了功能改变,并且据推测,这种减弱是由于GABA能篮状中间神经元因与兴奋性输入断开连接而“休眠”所致。在海马切片中,通过激活篮状细胞在CA1锥体细胞中诱发抑制性突触后电位(IPSP);将来自TLE动物模型的反应与来自对照组织的反应进行比较。在癫痫组织中,通过激活随后兴奋篮状细胞的终末间接诱发的IPSP减少,而当兴奋性神经传递被阻断时,通过直接激活篮状细胞诱发的IPSP与对照无异。这些结果为“休眠篮状细胞”假说提供了支持,并对人类TLE的病理生理学和治疗具有启示意义。