Wu C, Leung L S
Department of Clinical Neurological Sciences and Physiology, University of Western Ontario, London, Ontario, Canada N6A 5A5.
J Neurosci. 1997 Dec 1;17(23):9261-9. doi: 10.1523/JNEUROSCI.17-23-09261.1997.
The effect of partial hippocampal kindling, a model of temporal lobe seizure, on monosynaptic inhibition mediated by GABA was studied. Kindled rats were given 15 nonconvulsive hippocampal afterdischarges, and control rats were given low frequency or no stimulations. At 1-2 d after kindling, paired-pulse depression (PPD) of the IPSCs recorded in CA1 neurons in vitro was significantly smaller in kindled as compared with control rats. The difference in PPD persisted for at least 21 d after kindling. The decrease in PPD of the IPSCs after partial hippocampal kindling was likely caused by a reduced GABA autoinhibition after downregulation of presynaptic GABAB receptors. The GABAB antagonist CGP35348 (1 mM) suppressed PPD of the IPSCs more strongly in control than in kindled rats. Direct activation of the presynaptic GABAB receptors by baclofen suppressed the monosynaptic IPSCs significantly more in control than in kindled rats. The decay rate of a single-pulse IPSC was faster in kindled than in control rats on day 1 or day 21 after partial kindling. The difference in IPSC decay between kindled and control rats was found with or without a GABAB receptor antagonist. The low efficacy of the presynaptic GABAB receptors in kindled rats may provide compensatory stabilization of the postsynaptic membrane against further seizures or plasticity.
研究了颞叶癫痫模型——部分海马点燃对γ-氨基丁酸（GABA）介导的单突触抑制的影响。对点燃大鼠给予15次非惊厥性海马后放电，对对照大鼠给予低频刺激或不给予刺激。在点燃后1 - 2天，与对照大鼠相比，体外记录的CA1神经元中抑制性突触后电流（IPSCs）的配对脉冲抑制（PPD）在点燃大鼠中显著减小。PPD的差异在点燃后至少持续21天。部分海马点燃后IPSCs的PPD降低可能是由于突触前GABAB受体下调后GABA自身抑制作用减弱所致。GABAB拮抗剂CGP35348（1 mM）对对照大鼠IPSCs的PPD抑制作用比对点燃大鼠更强。巴氯芬直接激活突触前GABAB受体对对照大鼠单突触IPSCs的抑制作用比对点燃大鼠更显著。在部分点燃后第1天或第21天，点燃大鼠单脉冲IPSC的衰减速率比对照大鼠更快。在有或没有GABAB受体拮抗剂的情况下，均发现点燃大鼠与对照大鼠之间IPSC衰减存在差异。点燃大鼠中突触前GABAB受体的低效性可能为突触后膜提供代偿性稳定，以防止进一步发作或可塑性变化。
