DEPRESSION OF GLUTAMATERGIC AND GABAERGIC SYNAPTIC RESPONSES IN STRIATAL SPINY NEURONS BY STIMULATION OF PRESYNAPTIC GABA(B) RECEPTORS

被引:83
作者
NISENBAUM, ES
BERGER, TW
GRACE, AA
机构
[1] UNIV PITTSBURGH, CTR NEUROSCI, DEPT BEHAV NEUROSCI, PITTSBURGH, PA 15260 USA
[2] UNIV PITTSBURGH, CTR NEUROSCI, DEPT PSYCHIAT, PITTSBURGH, PA 15260 USA
关键词
BACLOFEN; CORTICOSTRIATAL SLICE; PRESYNAPTIC INHIBITION; QX-314; SACLOFEN;
D O I
10.1002/syn.890140306
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The influence of gamma-aminobutyric acid(B) (GABA(B)) receptor stimulation on the excitatory and inhibitory synaptic potentials and membrane properties of identified striatal spiny neurons was examined in a corticostriatal slice preparation. Stimulation of the subcortical white matter evoked a monosynaptic, excitatory postsynaptic potential (EPSP) and a polysynaptic, inhibitory postsynaptic potential (IPSP) in spiny neurons. The EPSP had two components: a large amplitude response which could be blocked by the kainate/quisqualate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 muM), and a small amplitude, long-duration depolarization which could be blocked by the N-methyl-D-aspartate receptor antagonist, d-(-)-2-amino-5-phosphonovaleric acid (APV, 100 muM). The IPSP was observed as a membrane depolarization when recorded from neurons at resting membrane potential. However, when neurons were injected with the Na+-channel blocker, QX-314, allowing cells to be depolarized above their spike thresholds, a prominent hyperpolarizing IPSP was readily observed which could be blocked by the GABA(A) antagonist, bicuculline (10-50 muM). This bicuculline-sensitive IPSP was responsible for the inhibition of EPSP amplitude and probability of spike discharge revealed using paired stimulation of the subcortical white matter. The amplitude of both the EPSP and the IPSP were depressed by the GABA(B) receptor agonist, p-chlorophenyl-GABA (baclofen, 0.5-100 muM) in a concentration-dependent manner. Baclofen also blocked paired stimulus inhibition of spike discharge. These effects of baclofen persisted in slices in which the cortex was removed and were reversed by the GABA(B) receptor antagonist, 3-amino-3-hydroxy-2-(4-chlorophenyl)-propanesulphonic acid (saclofen, 100-500 muM). In contrast to its profound influence on synaptic input, baclofen did not alter resting membrane potential, input resistance, membrane current-voltage relationship, or spike threshold of the cells recorded, and therefore did not appear to exert direct postsynaptic effects on the striatal spiny neurons. Taken together, these data indicate that the depressant effects of baclofen on EPSPs are mediated through GABA(B) receptors located on the terminals of glutamatergic afferents within the striatum. Moreover, the results suggest that the actions of baclofen on IPSPs and paired stimulus inhibition are produced by activation of GABA(B) receptors within the striatum at a site presynaptic to spiny neurons, either on the terminals of GABAergic afferents or on an interposed non-spiny GABAergic cell. Thus, GABA(B) hetero- and auto-receptors have the capacity to provide a negative feedback mechanism through which the major excitatory and inhibitory inputs to striatal spiny neurons are regulated. (C) 1993 Wiley-Liss, Inc.
引用
收藏
页码:221 / 242
页数:22
相关论文
共 68 条
  • [1] ARBUTHNOTT GW, 1985, J PHYSIOL-LONDON, V367, pP102
  • [2] THE PRESERVATION OF NERVE-CELLS IN RAT NEOSTRIATAL SLICES MAINTAINED INVITRO - A MORPHOLOGICAL-STUDY
    BAK, IJ
    MISGELD, U
    WEILER, M
    MORGAN, E
    [J]. BRAIN RESEARCH, 1980, 197 (02) : 341 - 353
  • [3] BARKER JL, 1986, J PHYSIOL-LONDON, V377, pP83
  • [4] REPLICATION OF THE NEUROCHEMICAL CHARACTERISTICS OF HUNTINGTONS-DISEASE BY QUINOLINIC ACID
    BEAL, MF
    KOWALL, NW
    ELLISON, DW
    MAZUREK, MF
    SWARTZ, KJ
    MARTIN, JB
    [J]. NATURE, 1986, 321 (6066) : 168 - 171
  • [5] A TYPE OF ASPINY NEURON IN THE RAT NEOSTRIATUM ACCUMULATES [H-3]GAMMA-AMINOBUTYRIC ACID - COMBINATION OF GOLGI-STAINING, AUTORADIOGRAPHY, AND ELECTRON-MICROSCOPY
    BOLAM, JP
    CLARKE, DJ
    SMITH, AD
    SOMOGYI, P
    [J]. JOURNAL OF COMPARATIVE NEUROLOGY, 1983, 213 (02) : 121 - 134
  • [6] GLUTAMATE DECARBOXYLASE-IMMUNOREACTIVE STRUCTURES IN THE RAT NEOSTRIATUM - A CORRELATED LIGHT AND ELECTRON-MICROSCOPIC STUDY INCLUDING A COMBINATION OF GOLGI IMPREGNATION WITH IMMUNOCYTOCHEMISTRY
    BOLAM, JP
    POWELL, JF
    WU, JY
    SMITH, AD
    [J]. JOURNAL OF COMPARATIVE NEUROLOGY, 1985, 237 (01) : 1 - 20
  • [7] GABA-A AND GABA-B RECEPTOR-SITE DISTRIBUTION IN THE RAT CENTRAL-NERVOUS-SYSTEM
    BOWERY, NG
    HUDSON, AL
    PRICE, GW
    [J]. NEUROSCIENCE, 1987, 20 (02) : 365 - 383
  • [8] SYNAPTIC AND INTRINSIC CONTROL OF MEMBRANE EXCITABILITY OF NEOSTRIATAL NEURONS .1. AN INVIVO ANALYSIS
    CALABRESI, P
    MERCURI, NB
    STEFANI, A
    BERNARDI, G
    [J]. JOURNAL OF NEUROPHYSIOLOGY, 1990, 63 (04) : 651 - 662
  • [9] INVOLVEMENT OF GABA SYSTEMS IN FEEDBACK-REGULATION OF GLUTAMATE-MEDIATED AND GABA-MEDIATED SYNAPTIC POTENTIALS IN RAT NEOSTRIATUM
    CALABRESI, P
    MERCURI, NB
    DEMURTAS, M
    BERNARDI, G
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1991, 440 : 581 - 599
  • [10] SYNAPTIC AND INTRINSIC CONTROL OF MEMBRANE EXCITABILITY OF NEOSTRIATAL NEURONS .2. AN INVITRO ANALYSIS
    CALABRESI, P
    MERCURI, NB
    BERNARDI, G
    [J]. JOURNAL OF NEUROPHYSIOLOGY, 1990, 63 (04) : 663 - 675