[Application of Paired-Pulse Stimulation for the Measurement of Inhibitory Transmission from the Hippocampal CA1...

Short-term modifications of postsynaptic responses to paired-pulse stimulation depend not only on presynaptic facilitation. IPSP generated immediately after EPSP in response to the first stimulus is superimposed to synaptic facilitation, decreasing PPF at the shortest interpulse intervals or even producing paired-pulse depression. This effect can be used to measure the efficacy of inhibitory transmission specifically in the hippocampal CA1 area. Comparison of paired-pulse ratio was performed by different methods for the better extraction of GABA(A) IPSP involvement into CA1 field potentials of the rat hippocampal slices. Paired-pulse stimuli were delivered with the set of different stimulus intensity and two interpulse intervals--70 and 15 ms. PPF changes in accordance with exponential decrease of presynaptic residual calcium were observed mainly at low stimuli intensities, but more intensive activation suppressed PPF15 relative to PPF70, sometimes up to paired-pulse depression. The difference of the second in pair amplitudes (A2(15)-A2(70)) upon stimulus intensity corresponded to linear function with a negative slope. The negativity disappeared after bicuculline treatment, suggesting the involvement of GABA(A) inhibition. Therefore individual gradients of these functions can be considered as the coefficients of inhibition to measure its modifications in on-line regime.