Affiliation:
1. Institut National de la Sante et de la Recherche Medicale, U-29,Paris, France.
Abstract
1. The possibility of long-lasting modifications of glutamatergic responses after anoxic-aglycemic (AA) episodes was investigated in CA1 hippocampal neurons of adult slices. Bicuculline (10 microM) was continuously bath applied to block GABAA receptor-mediated currents. AA episodes were induced by brief (1.30-3 min) perfusions with a glucose free artificial-cerebro-spinal-fluid (ACSF) saturated with 95% N2-5% CO2. 2. In presence of (0.6 mM) Mg2+ and a low concentration of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1 microM), the Schaffer collateral field EPSPs consisted of an early AMPA receptor-mediated component and a late N-methyl-D-aspartate (NMDA) receptor-mediated component. The former was blocked by (10 microM) CNQX and the latter by (50) microM D-2-amino-5-phosphonovalerate (D-APV). The AA episode induced a selective long-term potentiation (LTP) of the NMDA receptor-mediated component [+70 +/- 13% (mean +/- SE), P < or = 0.008, n = 9] without affecting significantly the AMPA receptor-mediated component (+2 +/- 4, P < or = 0.86 n = 9). This selective LTP is due to an enhanced efficacy of synaptic transmission and will be referred to as anoxic LTP. 3. In slices perfused with an ACSF containing a physiological concentration of (1.3 mM) Mg2+ and no CNQX, the intracellularly recorded excitatory postsynaptic potential (EPSP) was mixed (AMPA/NMDA) at -65 mV and exclusively mediated by AMPA receptors at -100 mV. At -65 mV, the AA episode induced a persistent potentiation of the EPSP (peak amplitude potentiated by 43 +/- 6%, P < or = 0.008, n = 9, 1 h after return to control ACSF). This potentiated component of the EPSP was fully sensitive to (50 microM) D-APV. The CNQX-sensitive AMPA receptor-mediated component was not affected by the AA episode (-5.7 +/- 6%, P < or = 0.123, n = 9). Furthermore, at -100 mV a large APV-sensitive component appeared after the AA episode (+58 +/- 18% of the peak amplitude, P < or = 0.018, n = 9). Therefore, the AA episode induced a selective LTP of the NMDA receptor-mediated component of the EPSP. 4. A robust LTP (+50.0 +/- 7.5%, P < or = 0.008, n = 12) of the NMDA receptor-mediated intracellular EPSP was also observed when AMPA receptors were fully and continuously blocked by (15 microM) CNQX.(ABSTRACT TRUNCATED AT 400 WORDS)
Publisher
American Physiological Society
Subject
Physiology,General Neuroscience
Cited by
120 articles.
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