Temporal overlap of excitatory and inhibitory afferent input in guinea-pig CA1 pyramidal cells

1. The temporal interaction of evoked synaptic excitation and GABAA-mediated inhibition was examined in CA1 pyramidal cells. Single and paired intracellular recordings were carried out in pyramidal cell dendrites and somata, and interneurons of the guinea-pig hippocampal slice. Current-clamp, sharp electrode and whole-cell voltage-clamp recordings were made. 2. Kinetics of dendritic and somatic inhibitory responses were similar. Notably, kinetics of dendritic unitary IPSPs were as fast as kinetics of somatic unitary IPSPs. 3. GABAA-mediated influences were present throughout the orthodromic pyramidal cell EPSP/EPSC. Comparison of the kinetics of pharmacologically isolated monosynaptic IPSPs, IPSCs and inhibitory conductances (g GABAA), showed fastest kinetics for g GABAA. Close temporal overlap was observed between monosynaptic g GABAA and the rising phase of the evoked EPSP/EPSC. The onset of g GABAA coincided with or preceded onset of the EPSP/EPSC. 4. Onsets of feedforward IPSPs coincided with the rising phase of the pyramidal cell EPSP in > 80 % of paired recordings. Fastest feedforward inhibitory responses exerted near complete overlap with evoked excitation. 5. Onsets of recurrent IPSPs did not occur during the rising phase of the evoked EPSP, but > 3.0 ms after the peak of the pyramidal cell EPSP. 6. Orthodromically evoked interneuron spikes were observed at stimulation intensities that were below the threshold for eliciting EPSPs in concomitantly recorded pyramidal cells. The activation of feedforward inhibitory responses by weakest excitatory input, and the large temporal overlap between feedforward inhibition and evoked excitation, suggest that in situ any excitatory input in CA1 is effectively controlled by fast synaptic inhibition.