BLOCKING GABA(A) INHIBITION REVEALS AMPA-RECEPTOR-MEDIATED AND NMDA-RECEPTOR-MEDIATED POLYSYNAPTIC RESPONSES IN THE CA1 REGION OF THE RAT HIPPOCAMPUS

Blocking GABA(A) inhibition reveals AMPA- and NMDA-receptor-mediated p olysynaptic responses in the CA1 region of the rat hippocampus. J. Neu rophysiol. 77: 2071-2082, 1997. We have investigated the conditions re quired to evoke polysynaptic responses in the isolated CA1 region of h ippocampal slices from Wistar adult rats. Experiments were performed w ith extracellular and whole cell recording techniques. In the presence of bicuculline (10 mu M), 6-cyano-7-nitroquinoxaline-2-3-dione (10 mu M), glycine (10 mu M), and a low external concentration of Mg2+ (0.3 mM), electrical stimulation of the Schaffer collaterals/commissural pa thway evoked graded N-methyl-D-aspartate (NMDA) 1-receptor-mediated la te field potentials in the stratum radiatum of the CA1 region. These r esponses were generated via polysynaptic connections because their lat ency 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 mu M) in the stratum oriens strongly reduced the late synaptic co mponent and antidromic stimulation of CA1 pyramidal cells could evoke the polysynaptic response. Current-source density analysis suggested t hat the polysynaptic response was generated along the proximal part of the apical dendrites of CA1 pyramidal cells (50-150 mu m below the py ramidal cell layer in the stratum radiatum). In physiological concentr ation of Mg2+ (1.3 mM), the pharmacologically isolated NMDA-receptor-m ediated polysynaptic response was abolished. In control artificial cer ebrospinal fluid (with physiological concentration of Mg2+), bicuculli ne (10 mu M) generated a graded polysynaptic response. Under these con ditions, this response was mediated both by lpha-amino-3-hydroxy-5-met hyl-4-isoxazolepropionic acid (AMPA)/NMDA receptors. In the presence o f D-2-amino-5-phosphonovalerate (50 mu M), the polysynaptic response c ould be mediated by AMPA receptors, although less efficiently. In conc lusion, suppression of gamma-aminobutyric acid-A inhibition reveals gl utamate receptor-mediated network-driven events in the isolated CA1 re gion. These polysynaptic responses are mediated by AMPA and/or NMDA re ceptors depending on the pharmacological conditions and the external c oncentration of Mg2+ used. We suggest that these responses are driven by local recurrent collaterals of CA1 pyramidal cells.