Blocking GABA-A inhibition reveals AMPA and NMDA receptor-mediated polysynaptic responses in the CA1 region of the rat hippocampus. V. CrŽpel, R. Khazipov and Y. Ben-Ari. INSERM U 29, 123 Boulevard de Port-Royal and UniversitŽ RenŽ Descartes, 75674 Paris cedex 14 France.
APStracts 4:0017N, 1997.
ABSTRACT
1. We have investigated the conditions required to evoke polysynaptic responses in the isolated CA1 region of hippocampal slices from Wistar adult rats. Experiments were performed with extracellular and whole-cell recording techniques. 2. In the presence of bicuculline (10 ĉM), CNQX (10 ĉM), glycine (10 ĉM) and a low external concentration of Mg2+ (0.3 mM), electrical stimulation of the Schaffer collaterals/commissural pathway evoked graded NMDA receptor-mediated late field potentials in the stratum radiatum of the CA1 region. These responses were generated via polysynaptic connections since: (i) their latency varied strongly and inversely with the stimulation intensity; (ii) they were abolished by a high concentration of divalent cations (7 mM Ca2+). 3. These responses were likely driven by local collateral branches of CA1 pyramidal cell axons, since (i) focal application of tetrodotoxin (30 ĉM) in the stratum oriens strongly reduced the late synaptic component; (ii) antidromic stimulation of CA1 pyramidal cells could evoke the polysynaptic response. 4. Current-source density analysis suggested that the polysynaptic response was generated along the proximal part of the apical dendrites of CA1 pyramidal cells (50-150 ĉm below the pyramidal cell layer in the stratum radiatum). 5. The pharmacollogically isolated NMDA receptor-mediated polysynaptic response was abolished in physiological concentration of Mg2+ (1.3 mM) 6. In control ACSF (with physiological concentration of Mg2+), bicuculline (10 ĉM) generated a graded polysynaptic response. Under these conditions, this response was mediated both by AMPA/NMDA receptors. In the presence of D-APV (50 ĉM), the polysynaptic response could be mediated by AMPA receptors, although less efficiently. 7. In conclusion, suppression of GABA-A inhibition reveals glutamate receptor- mediated network-driven events in the isolated CA1 region. These polysynaptic responses are mediated by AMPA and/or NMDA receptors depending on the pharmacological conditions and the external concentration of Mg2+ used. We suggest that these responses are driven by local recurrent collaterals of CA1 pyramidal cells. 

Received 12 August 1996; accepted in final form 26 December 1996.
APS Manuscript Number J635-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 24 January 1997