Adenosine suppresses presynaptic release probability of excitatory connections in layer 6 of the mPFC via A1ARs. A, Top, schematic representation of a mPFC slice with the position of the paired-recording electrodes. Bottom, pre- and postsynaptic firing patterns are shown in in brown and black, respectively. B, Current clamp recordings of unitary synaptic connections in layer 6 of rat mPFC. Five consecutive uEPSPs (middle, light gray) and the average EPSP (bottom, black) are elicited by two presynaptic APs at 10 Hz (top, brown). C, Time course of EPSP amplitude change following bath application of 30 μM adenosine to a L6 excitatory connection. Dashed lines indicate the mean first EPSP amplitude under control and adenosine conditions. D, Summary data of several EPSP properties for L6 excitatory connections are shown. Error bars represent SD. NS (not significant), **p < 0.01, ***p < 0.001 for Wilcoxon signed-rank test. n = 15 pairs from 15 rats. E, Top, superimposition of EPSPs recorded in control, the presence of Ado (30 μM), and of Ado and CPT (1 μM) from a representative excitatory connection in layer 6 of rat mPFC. Bottom, time course of EPSP amplitude changes following bath application of 30 μM adenosine (ADO) and of adenosine and CPT (ADO&CPT) in the same excitatory pair. F, Histograms (n = 9 pairs from 9 rats) showing the effect of adenosine (ADO) and CPT blockade of adenosine-induced changes (ADO&CPT) on several EPSP properties including EPSP amplitude, PPR, CV, and failure rate. Error bars represent SD. *p < 0.05, **p < 0.01, ***p < 0.001 for Wilcoxon signed-rank test. G, Superimposition of EPSPs recorded in control and the presence of CGS21680 (30 nM) from a representative excitatory connection in layer 6 of rat mPFC. H, Time course of EPSP amplitude change during application of CGS21680. I, Summary data of CGS21680-induced changes in EPSP properties (n = 3 pairs from 3 rats). NS, not significant for paired t test.
