Quantitative assessment of the effect of CNQX on paired-pulse facilitation in the anterior cingulate cortex

Paired-pulse facilitation (PPF) is a form of short-term plasticity which has been used qualitatively to characterize the action of neuroactive compounds. The aims of the present study were to develop a model that allows the quantitative assessment of PPF and to evaluate the influence of CNQX, an AMPA receptor antagonist, on synaptic plasticity based on parameters derived from this model. Experiments were performed on brain slices taken from the coronal anterior cingulate cortex (ACC) of Sprague-Dawley rats. Stimulation was applied to layer 5 of the ACC. In all experiments, the stimuli comprised a pair of biphasic pulses generated by an isolated pulse stimulator under software control. An inter-pulse interval of 40 ms was employed, and the evoked extracellular field potentials in layer 2/3 of the ACC were recorded. An equation was adopted to describe the PPF at different stimulation intensities. Nonlinear fitting was used to obtain the coefficients of the equation which would allow the description of the experimental data. CNQX exerted an influence on the area under the curve for the PPF versus stimulation plot by changing the values of the parameter K (the voltage causing a half-maximal response). The model was elaborated based on features of the ligand–receptor interaction which can be reliably specified empirically, and its applicability was illustrated by characterizing the influence of CNQX on PPF in the ACC. An algorithm for the assessment of PPF using different sets of parameters is also discussed.