CNQX increases spontaneous inhibitory input to CA3 pyramidal neurones in neonatal rat hippocampal slices

Whole-cell recordings were made from immature CA3 pyramidal neurones in the rat hippocampal slice. The addition of the glutamate receptor antagonist, CNQX, caused a robust increase in the frequency of spontaneous inhibitory post-synaptic currents (IPSC) concomitant with the expected reduction of excitatory drive to these neurones. This effect of CNQX was not shared by structurally related quinoxalinediones or kynurenic acid, which are also antagonists of non-NMDA glutamate receptors. This effect of CNQX was abolished by tetrodotoxin suggesting that an increase in interneurone spiking was responsible for the IPSCs. Recordings from stratum radiatum interneurones of CA3 confirmed this suggestion, since some interneurones were directly depolarized by CNQX. The excitation by CNQX of a small population of stratum radiatum interneurones of CA3 complicates interpretation of experiments designed to assess the consequences of blocking excitatory transmission with this drug.