Complex effects of CNQX on CA1 interneurons of the developing rat hippocampus

We have investigated the effect of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), on spontaneous GABA_A receptor-mediated transmission in the hippocampal CA1 subfield. On average, simultaneous recordings from CA1 str. radiatum interneurons and pyramidal cells showed that CNQX application doubled the frequency of bicuculline sensitive spontaneous inhibitory postsynaptic currents (sIPSCs) without apparently changing their amplitude. However, despite the increase in sIPSC frequency, current-clamp recording showed that CNQX application was sufficient in most cases to depolarize interneurons to firing threshold. In contrast, CNQX application could not induce firing in pyramidal cells. In the presence of tetrado-toxin (TTX), CNQX increased interneuron membrane conductance, and depolarized interneurons from resting potentials. The axons of the studied interneurons ramify widely in the CA1 region and suggest that the cells of our sample are mostly involved with control of dendritic excitability. Our results indicate that CNQX-induced increase of sIPSC frequency is not limited to excitatory cells, but also impacts GABAergic interneurons. However, despite the increase of sIPSC frequency, CNQX-induced depolarization is sufficient to selectively generate firing in interneurons and thus modify the network properties mediated by GABA_A receptors in the hippocampus.