Differential presynaptic modulation of excitatory and inhibitory autaptic currents in cultured hippocampal neurons

被引:12
|
作者
Thio, LL
Yamada, KA
机构
[1] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Ctr Study Nervous Syst Injury, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
[4] St Louis Childrens Hosp, Div Pediat Neurol, St Louis, MO 63110 USA
[5] St Louis Childrens Hosp, Pediat Epilepsy Ctr, St Louis, MO 63110 USA
关键词
short-term plasticity; spillover; silent synapse; conduction block; hyperpolarizing prepulse;
D O I
10.1016/j.brainres.2004.02.077
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Short-term synaptic plasticity has an important role in higher cortical function. Hyperpolarization may effect a form of short-term plasticity by promoting recovery from sodium channel inactivation or by activating axonal A-type potassium channels. To determine whether one or both processes occur, we examined the effect of hyperpolarizing prepulses on autaptic currents in cultured postnatal rat hippocampal neurons. As expected of enhanced recovery from sodium channel inactivation, hyperpolarizing prepulses reversibly increased fast excitatory autaptic currents (eacs) mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), slow eacs mediated by N-methyl-D-aspartate receptors (NMDARs), and inhibitory autaptic currents (iacs) mediated by gamma-aminobutyric acid(A) receptors (GABA(A)Rs). Hyperpolarizing prepulses augmented nearly all fast and slow eacs but only half of the iacs. This change occurred without a change in autaptic current kinetics. Of note, hyperpolarizing prepulses did not significantly reduce autaptic currents in any neuron studied. The rapidly dissociating competitive antagonists kynurenate and L-2-amino-5-phosphonovaleric acid (LAPV) inhibited fast and slow eacs, respectively, to the same extent with and without a hyperpolarizing prepulse. In addition, hyperpolarizing prepulses revealed a slow eac even after the slow eac evoked without a prepulse was completely blocked by the open channel blocker, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801). Finally, hyperpolarizing prepulses did not alter currents evoked by exogenous applications of glutamate and GABA. These findings suggest that hyperpolarizing prepulses preferentially enhance eacs over iacs, and that they do so, in part, by overcoming conduction block or by activating silent synapses. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:22 / 28
页数:7
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