Forti M, Biella G, Caccia S, de Curtis M
Department of Neurophysiology, Istituto Nazionale Neurologico, Milan, Italy.
Eur J Neurosci. 1997 Mar;9(3):435-51. doi: 10.1111/j.1460-9568.1997.tb01621.x.
The development of long-lasting excitability changes after a single intracerebral injection of bicuculline (1 mM) in a restricted region of the anterior piriform cortex was studied by means of simultaneous intra- and extracellular recordings in the isolated guinea-pig brain preparation maintained in vitro by arterial perfusion. The transitory disinhibition induced by bicuculline revealed transient afterdischarges that were followed by the activation of a synaptic potential mediated by the recurrent propagation of the focal epileptiform activity along cortico-cortical associative fibres. The epileptiform associative potential persisted for the duration of the experiment. Both the induction and the long-term expression of the epileptiform associative potential were dependent on the activation of glutamatergic receptors of the NMDA type, as demonstrated by perfusion with the NMDA receptor antagonist 2-aminopentanoic acid (AP5) (100 microM). After bicuculline washout, piriform cortex neurons responded to afferent stimulation with a burst discharge superimposed on a paroxysmal depolarizing potential. The early component of the burst was mediated by a Ca(2+)-dependent, non-synaptic potential located at the proximal apical dendrites and soma of layer II-III cells, since (i) it was abolished by membrane hyperpolarization, (ii) it was not affected by AP5, (iii) it was correlated with a current sink in layer II, as demonstrated by current source density analysis of field potential laminar profiles, and (iv) it was abolished by cadmium (2-5 mM) applied locally in layer II. The late component of the burst response (i) coincided in time with the extracellular epileptiform associative potential, (ii) increased linearly in amplitude during membrane hyperpolarization, (iii) was blocked by AP5, and (iv) was correlated with an extracellular sink in layer Ib, where the associative fibres contact the distal apical dendrites of piriform cortex neurons. The results presented here indicate that a transient focal disinhibition promotes persistent intrinsic and synaptic excitability changes in piriform cortex neurons. These changes may be responsible for the propagation of epileptiform activity and for the induction of secondary epileptogenesis.
通过在体外动脉灌注维持的离体豚鼠脑制备物中同时进行细胞内和细胞外记录，研究了在前梨状皮层受限区域单次脑内注射荷包牡丹碱（1 mM）后持久兴奋性变化的发展情况。荷包牡丹碱诱导的短暂去抑制揭示了短暂的后放电，随后是由局灶性癫痫样活动沿皮质 - 皮质联合纤维的反复传播介导的突触电位的激活。癫痫样联合电位在实验期间持续存在。如用NMDA受体拮抗剂2 - 氨基戊酸（AP5）（100 microM）灌注所证明的，癫痫样联合电位的诱导和长期表达均依赖于NMDA型谷氨酸能受体的激活。荷包牡丹碱洗脱后，梨状皮层神经元对传入刺激的反应是在阵发性去极化电位上叠加爆发性放电。爆发的早期成分由位于II - III层细胞近端顶端树突和胞体的钙依赖性非突触电位介导，因为（i）它被膜超极化消除，（ii）它不受AP5影响，（iii）通过场电位层状分布的电流源密度分析表明它与II层中的电流汇相关，并且（iv）它被局部应用于II层的镉（2 - 5 mM）消除。爆发反应的晚期成分（i）在时间上与细胞外癫痫样联合电位一致，（ii）在膜超极化期间幅度呈线性增加，（iii）被AP5阻断，并且（iv）与Ib层中的细胞外电流汇相关，联合纤维在此处接触梨状皮层神经元的远端顶端树突。此处呈现的结果表明，短暂的局灶性去抑制促进了梨状皮层神经元中持久的内在和突触兴奋性变化。这些变化可能是癫痫样活动传播和继发性癫痫发生诱导的原因。
