The Journal of Neurophysiology Vol. 77 No. 4 April 1997, pp. 2071-2082
Copyright ©1997 The American Physiological Society

Blocking GABA_A Inhibition Reveals AMPA- and NMDA-Receptor-Mediated Polysynaptic Responses in the CA1 Region of the Rat Hippocampus

V. Crépel, R. Khazipov, and Y. Ben-Ari

Institut National de la Santé et de la Recherche Médicale U 29; and Université René Descartes, 75674 Paris cedex 14, France

Crépel, V., R. Khazipov, and Y. Ben-Ari. Blocking GABA_A inhibition reveals AMPA- and NMDA-receptor-mediated polysynaptic responses in the CA1 region of the rat hippocampus. J. Neurophysiol. 77: 2071-2082, 1997. 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. In the presence of bicuculline (10 µM), 6-cyano-7-nitroquinoxaline-2-3-dione (10 µM), glycine (10 µM), and a low external concentration of Mg²⁺ (0.3 mM), electrical stimulation of the Schaffer collaterals/commissural pathway evoked graded N-methyl-D-aspartate (NMDA)-receptor-mediated late field potentials in the stratum radiatum of the CA1 region. These responses were generated via polysynaptic connections because their latency varied strongly and inversely with the stimulation intensity and they were abolished by a high concentration of divalent cations (7 mM Ca²⁺). These responses likely were driven by local collateral branches of CA1 pyramidal cell axons because focal application of tetrodotoxin (30 µM) in the stratum oriens strongly reduced the late synaptic component and antidromic stimulation of CA1 pyramidal cells could evoke the polysynaptic response. 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 µm below the pyramidal cell layer in the stratum radiatum). In physiological concentration of Mg²⁺ (1.3 mM), the pharmacologically isolated NMDA-receptor-mediated polysynaptic response was abolished. In control artificial cerebrospinal fluid (with physiological concentration of Mg²⁺), bicuculline (10 µM) generated a graded polysynaptic response. Under these conditions, this response was mediated both by -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA receptors. In the presence of D-2-amino-5-phosphonovalerate (50 µM), the polysynaptic response could be mediated by AMPA receptors, although less efficiently. In conclusion, suppression of -aminobutyric acid-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.

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