Hu Bin, Karnup Sergei, Zhou Lei, Stelzer Armin
Department of Physiology and Pharmacology, State University of New York, 450 Clarkson Ave., Box 29, Brooklyn, New York 11203, USA.
J Neurophysiol. 2005 Jan;93(1):316-36. doi: 10.1152/jn.00172.2004. Epub 2004 Jul 28.
Memory impairment is a common consequence of epileptic seizures. The hippocampal formation is particularly prone to seizure-induced amnesia due to its prominent role in mnemonic processes. We used the isolated CA1 slice preparation to examine effects of seizure-like activity on hippocampal plasticity, long-term potentiation (LTP), and long-term depression (LTD). Repeated spontaneous ictal events, generated in the presence of antagonists of GABA(A) receptor function, led to a stepwise erasure of LTP (termed spontaneous depotentiation, SDP). SDP could be initiated at various stages of LTP consolidation (tested < or =120 min after the induction of LTP). Renewed tetanic stimulation re-established LTP. SDP was remarkably specific: baseline transmission and other forms of hippocampal plasticity, i.e., Ca(2+)-induced LTP and two forms of LTD [(RS)-3,5-dihydroxyphenyglycine (DHPG) mediated and low-frequency stimulation mediated] were not affected by the same type of seizure activity. SDP was blocked in the presence of the group I mGluR antagonist (S)-4-carboxyphenylglycine. The mGluR1 antagonist (S)-(+)-alpha-amino-methylbenzeneacetic acid blocked approximately 80%, the mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)-pyridine approximately 30% of SDP. Most efficient implementation of SDP was observed during seizures in the combined presence of the group I mGluR agonist DHPG and the GABA(A) antagonist bicuculline. However, similar ictal activity generated in the presence of DHPG alone did not lead to SDP in the vast majority of recordings. Complete disinhibition and at least partial activation of group I mGluR were necessary conditions for the induction of SDP. The depotentiating pharmacological conditions were accompanied by tonic membrane depolarization of CA1 pyramidal cells. Since hyperpolarization (by negative current injection) prevented intracellular SDP under depotentiating pharmacological conditions and depolarization (by positive current injection) led to selective intracellular SDP in the non-depotentiating seizure protocol of DHPG, it is concluded that cell depolarization was a sufficient condition for seizure-like activity to reverse hippocampal LTP.
记忆障碍是癫痫发作的常见后果。海马结构因其在记忆过程中的突出作用，特别容易发生由癫痫发作引起的失忆。我们使用离体CA1脑片标本，来研究癫痫样活动对海马可塑性、长时程增强（LTP）和长时程抑制（LTD）的影响。在存在GABA(A)受体功能拮抗剂的情况下产生的反复自发性发作事件，导致LTP的逐步消除（称为自发性去增强，SDP）。SDP可在LTP巩固的各个阶段启动（在LTP诱导后≤120分钟进行测试）。再次强直刺激可重新建立LTP。SDP具有显著的特异性：基线传递和其他形式的海马可塑性，即钙诱导的LTP和两种形式的LTD [（RS）-3,5-二羟基苯甘氨酸（DHPG）介导的和低频刺激介导的]不受相同类型癫痫活动的影响。在存在I组代谢型谷氨酸受体（mGluR）拮抗剂（S）-4-羧基苯甘氨酸的情况下，SDP被阻断。mGluR1拮抗剂（S）-（+）-α-氨基甲基苯乙酸阻断了约80%的SDP，mGluR5特异性拮抗剂2-甲基-6-（苯乙炔基）-吡啶阻断了约30%的SDP。在I组mGluR激动剂DHPG和GABA(A)拮抗剂荷包牡丹碱同时存在的癫痫发作期间，观察到SDP最有效的发生。然而，在绝大多数记录中，仅在存在DHPG的情况下产生的类似发作活动并未导致SDP。完全去抑制和I组mGluR的至少部分激活是诱导SDP的必要条件。去增强的药理学条件伴随着CA1锥体细胞的强直膜去极化。由于超极化（通过负电流注入）在去增强的药理学条件下阻止了细胞内SDP，而去极化（通过正电流注入）在DHPG的非去增强癫痫发作方案中导致了选择性细胞内SDP，因此得出结论，细胞去极化是癫痫样活动逆转海马LTP的充分条件。
Neuropharmacology. 2005-6
PLoS One. 2007-11-28
Zotero 插件