Presynaptic inactivation of action potentials and postsynaptic inhibition of GABAA currents contribute to KA-induced disinhibition in CA1 pyramidal neurons

被引:13
作者
Kang, N
Jiang, L
He, W
Xu, J
Nedergaard, M
Kang, J
机构
[1] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA
[2] Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
[3] Univ Rochester, Med Ctr, Ctr Aging & Dev Biol, Rochester, NY 14642 USA
关键词
D O I
10.1152/jn.01231.2003
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Kainate-type glutamate ionotropic receptors (KAR) mediate either depression or potentiation of inhibitory transmission. The mechanisms underlying the depressant effect of KAR agonists have been controversial. Under dual patch-clamp recording techniques in synaptically coupled pairs of CA1 interneurons and pyramidal neurons in hippocampal slices, micromolar concentrations of KAR agonists, kainic acid (KA, 10 muM) and ATPA (10 muM), induced inactivation of action potentials (APs) in 58 and 50% of presynaptic interneurons, respectively. Inactivation of interneuronal APs might have significantly contributed to KA-induced decreases in evoked inhibitory postsynaptic currents (eIPSCs) that are obtained by stimulating the stratum radiatum. With controlled interneuronal APs, KAR agonists induced a decrease in the potency ( mean amplitude of successful events) and mean amplitude ( including failures) of unitary inhibitory postsynaptic currents (uIPSCs) without significantly changing the success rate (P-s) at perisomatic high-P-s synapses. In contrast, KAR agonists induced a decrease in both the P-s and potency of uIPSCs at dendritic high-P-s synapses. KAR agonists induced an inhibition of GABA(A) currents by activating postsynaptic KARs in pyramidal neurons; this was more prominent at dendrites than at soma. Both the exogenous GABA-induced current and the amplitude of miniature IPSCs (mIPSCs) were attenuated by KAR agonists. Thus the postsynaptic KAR-mediated inhibition of GABA(A) currents may contribute to the KAR agonist-induced decrease in the potency of uIPSCs and KA-induced disinhibition.
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页码:873 / 882
页数:10
相关论文
共 72 条
[1]   GABA-MEDIATED BIPHASIC INHIBITORY RESPONSES IN HIPPOCAMPUS [J].
ALGER, BE ;
NICOLL, RA .
NATURE, 1979, 281 (5729) :315-317
[2]   PHARMACOLOGICAL EVIDENCE FOR 2 KINDS OF GABA RECEPTOR ON RAT HIPPOCAMPAL PYRAMIDAL CELLS STUDIED INVITRO [J].
ALGER, BE ;
NICOLL, RA .
JOURNAL OF PHYSIOLOGY-LONDON, 1982, 328 (JUL) :125-141
[3]   Kainate receptors regulate unitary IPSCs elicited in pyramidal cells by fast-spiking interneurons in the neocortex [J].
Ali, AB ;
Rossier, J ;
Staiger, JF ;
Audinat, E .
JOURNAL OF NEUROSCIENCE, 2001, 21 (09) :2992-2999
[4]   2 DIFFERENT RESPONSES OF HIPPOCAMPAL PYRAMIDAL CELLS TO APPLICATION OF GAMMA-AMINO BUTYRIC-ACID [J].
ANDERSEN, P ;
DINGLEDINE, R ;
GJERSTAD, L ;
LANGMOEN, IA ;
LAURSEN, AM .
JOURNAL OF PHYSIOLOGY-LONDON, 1980, 305 (AUG) :279-296
[5]  
Beck J, 2003, J NEUROSCI, V23, P5061
[6]   Kainate, a double agent that generates seizures: two decades of progress [J].
Ben-Ari, Y ;
Cossart, R .
TRENDS IN NEUROSCIENCES, 2000, 23 (11) :580-587
[7]   Kainate receptor (GluR5)-mediated disinhibition of responses in rat ventrobasal thalamus allows a novel sensory processing mechanism [J].
Binns, KE ;
Turner, JP ;
Salt, TE .
JOURNAL OF PHYSIOLOGY-LONDON, 2003, 551 (02) :525-537
[8]   DIVERSE SOURCES OF HIPPOCAMPAL UNITARY INHIBITORY POSTSYNAPTIC POTENTIALS AND THE NUMBER OF SYNAPTIC RELEASE SITES [J].
BUHL, EH ;
HALASY, K ;
SOMOGYI, P .
NATURE, 1994, 368 (6474) :823-828
[9]  
Bureau I, 1999, J NEUROSCI, V19, P653
[10]  
CARLSON G, 2002, J NEUROSCI, V22, P3864