AGONISTS AT METABOTROPIC GLUTAMATE RECEPTORS PRESYNAPTICALLY INHIBIT EPSCS IN NEONATAL RAT HIPPOCAMPUS

被引:433
作者
BASKYS, A
MALENKA, RC
机构
[1] UNIV CALIF SAN FRANCISCO, DEPT PHYSIOL, SAN FRANCISCO, CA 94143 USA
[2] UNIV CALIF SAN FRANCISCO, DEPT PSYCHIAT, SAN FRANCISCO, CA 94143 USA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1991年 / 444卷
关键词
D O I
10.1113/jphysiol.1991.sp018901
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. The effects of metabotropic glutamate receptor agonists on excitatory synaptic transmission in the CA1 region of rat hippocampal slices (11-30 days) were studied using extracellular and whole-cell patch-clamp recording techniques. 2. Trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD; 25-100-mu-M) reversibly depressed excitatory postsynaptic currents (EPSCs) without affecting presynaptic fibre excitability or EPSC reversal potential. 3. Ibotenate (25-mu-M) or L-glutamate (250-mu-M), in the presence of the N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV, 50-75-mu-M), depressed the EPSC amplitude while inducing no detectable inward current. L-2-Amino-4-phosphonobutyrate (L-AP4, 25-100-mu-M), the phosphonic derivative of glutamate, also depressed EPSC amplitude and caused no detectable inward current. 4. The NMDA receptor-mediated component of the EPSC recorded in the presence of the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20-30-mu-M) was depressed by trans-ACPD, L-AP4, or quisqualate (1-2-mu-M). 5. The response to ionophoretic application of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) was unaffected by trans-ACPD or L-AP4 although the simultaneously recorded EPSC was strongly depressed. In addition, paired-pulse facilitation (50-75 ms interstimulus interval) was reversibly enhanced by trans-ACPD or L-AP4. These results indicate that the depression of synaptic transmission likely was mediated by a presynaptic 'autoreceptor'. 6. The effects of trans-ACPD or L-AP4 on synaptic transmission decreased significantly over ages 12-30 days and were minimal in adult (> 80 days) slices. 7. The depression of synaptic transmission caused by trans-ACPD or L-AP4 was not altered following the induction of long-term potentiation (LTP). 8. The results indicate that metabotropic glutamate receptor agonists suppress excitatory synaptic transmission in CA1 pyramidal cells by an action at a presynaptic
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收藏
页码:687 / 701
页数:15
相关论文
共 39 条
[1]   THE NON-NMDA RECEPTORS - TYPES, PROTEIN-STRUCTURE AND MOLECULAR-BIOLOGY [J].
BARNARD, EA ;
HENLEY, JM .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1990, 11 (12) :500-507
[2]   TRANS-ACPD DEPRESSES SYNAPTIC TRANSMISSION IN THE HIPPOCAMPUS [J].
BASKYS, A ;
MALENKA, RC .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 193 (01) :131-132
[3]   NMDA AND QUISQUALATE REDUCE A CA-DEPENDENT K+ CURRENT BY A PROTEIN KINASE-MEDIATED MECHANISM [J].
BASKYS, A ;
BERNSTEIN, NK ;
BAROLET, AW ;
CARLEN, PL .
NEUROSCIENCE LETTERS, 1990, 112 (01) :76-81
[4]  
BEKKERS J, 1990, NATURE, V346, P742
[5]   WHOLE CELL RECORDING FROM NEURONS IN SLICES OF REPTILIAN AND MAMMALIAN CEREBRAL-CORTEX [J].
BLANTON, MG ;
LOTURCO, JJ ;
KRIEGSTEIN, AR .
JOURNAL OF NEUROSCIENCE METHODS, 1989, 30 (03) :203-210
[6]   POTASSIUM CONDUCTANCES IN HIPPOCAMPAL-NEURONS BLOCKED BY EXCITATORY AMINO-ACID TRANSMITTERS [J].
CHARPAK, S ;
GAHWILER, BH ;
DO, KQ ;
KNOPFEL, T .
NATURE, 1990, 347 (6295) :765-767
[7]   NMDA RECEPTOR AGONISTS SELECTIVELY BLOCK N-TYPE CALCIUM CHANNELS IN HIPPOCAMPAL-NEURONS [J].
CHERNEVSKAYA, NI ;
OBUKHOV, AG ;
KRISHTAL, OA .
NATURE, 1991, 349 (6308) :418-420
[8]   MEASUREMENT OF PASSIVE MEMBRANE PARAMETERS WITH WHOLE-CELL RECORDING FROM NEURONS IN THE INTACT AMPHIBIAN RETINA [J].
COLEMAN, PA ;
MILLER, RF .
JOURNAL OF NEUROPHYSIOLOGY, 1989, 61 (01) :218-230
[9]  
COLLINGRIDGE GL, 1989, PHARMACOL REV, V41, P143
[10]   EFFECTS OF EXCITATORY AMINO-ACID ANTAGONISTS ON EVOKED AND SPONTANEOUS EXCITATORY POTENTIALS IN GUINEA-PIG HIPPOCAMPUS [J].
COTMAN, CW ;
FLATMAN, JA ;
GANONG, AH ;
PERKINS, MN .
JOURNAL OF PHYSIOLOGY-LONDON, 1986, 378 :403-415