Two inputs (input 1 and input 2) converging into the same CA1 pyramidal cell were alternately activated (pair of stimuli at 50 ms interval) at 0.25 Hz. AMPA-mediated EPSCs were recorded at −60 mV. A, schematic diagram showing localization of stimulating and recording electrodes. Sch, Schaffer collaterals; mf, mossy fibre; pp, perforant path; DG, dendate gyrus; EC, entorhinal cortex. B, time course of the amplitude of the EPSCs evoked before and after nicotine application (bar). Input 1: synapse presynaptically silent; in control conditions only response failures were detected to the first stimulus and few responses to the second one. Application of nicotine (bar) induced the appearance of synaptic currents that persisted for at least 30 min after nicotine application. Insets represent 10 consecutive traces recorded in control and 20 min after nicotine. C, input 2: synapse with high initial release probability. Nicotine (bar) strongly increased the number of transmitter failures and reduced the amplitude of the first and second EPSC. Insets represent 10 consecutive traces recorded in control and 20 min after nicotine.

A, the difference between the probability of successes obtained 20 min after nicotine application and that obtained in control (ΔP successes (Nic-control); ordinate; n = 59) is plotted against the initial probability of successes (P successes (control); abscissa). It is clear from the graph that synaptic responses with initial P below 0.25 exhibit ΔP successes (Nic-control) equal to or above 0 while synaptic responses with initial P above 0.35 exhibited ΔP successes (Nic-control) below 0. An intermediate group with initial P between 0.25 and 0.35 (marked by two arrows) exhibit ΔP successes (Nic-control) above and below 0. The correlation coefficient for the plot is 0.66 (p < 0.00001). B, the three groups in A are represented separately. Open symbols represent individual P-values before (control) and 20 min after nicotine application while filled symbols represent average P-values. In this and the following figures error bars refer to s.e.m.

A, average (upper) and six superimposed individual traces (lower) evoked by a pair of stimuli (50 ms a part) delivered to the Schaffer collateral 10 min (left) and 35 min (right) after the beginning of the recording. In this and the following figures, average traces include successes and failures. B, time course of the amplitude of the first (filled circles) and second (open circles) EPSCs evoked in control conditions (in the absence of nicotine application). Note the stability of synaptic currents without decrement throughout the experiment. C, average (upper) and eight superimposed individual traces (lower) evoked before (left) and 20 min after nicotine (right). Note increase in failure rate and decrease in EPSC amplitude after nicotine. D, time course of the amplitude of the first (filled circles) and second (open circles) EPSCs evoked before and after nicotine application (bar).

A, average time course (13 cells) of the amplitude of AMPA-mediated EPSCs normalized to their control (dashed line) before and after nicotine (bar). B, bath application of DHβE (10 μm; open bar) prevents the action of nicotine (filled bar) on AMPA-mediated EPSCs (normalized to their controls, dashed line; n = 6). In A and B, each bin is 1 min. C, each column represents nicotine-induced changes (normalized to control values, dotted line) in the amplitude, success rate, paired pulse ratio (PPR) and coefficient of variation (CV) for 20 cells. The increase in CV and PPR suggest a presynaptic site of action of nicotine-induced synaptic depression. *p < 0.05, **p < 0.01.

A, NMDA-mediated EPSCs evoked at +40 mV by minimal stimulation of the Schaffer collaterals, in the presence of DNQX (20 μm) and bicuculline (5 μm). Average traces (upper) and 10 consecutive superimposed traces (lower) obtained 10 min (left) and 80 min (right) after the beginning of the recording are shown in the insets. Note the stability of the recordings without decrement of NMDA-mediated synaptic currents with time. B, NMDA-mediated EPSCs evoked at +40 mV by minimal stimulation of the Schaffer collaterals, before, during (filled bar) and after nicotine. Note that nicotine induced a persistent depression of synaptic currents (in the insets average traces and 10 consecutive superimposed traces obtained in control and 20 min after nicotine). C, average time course of the amplitude of NMDA-mediated EPSCs normalized to their control (dashed line) before and after nicotine (bar). Each bin is 1 min (n = 11). D, mean amplitude of NMDA-mediated EPSCs (successes plus failures) before and after nicotine (n = 11). E, average success rate of NMDA-mediated EPSCs in control and after nicotine application (n = 11). **p < 0.01.

A, in high P (> 0.35) synapses nicotine-induced changes in the number of successes (to the first pulse) obtained in the presence DHβE (1 μm, white column), α-BGT (100 nm, grey column) or DHβE (1 μm) plus α-BGT (100 nm, black column) are normalized to the control values (dashed line). Note that in the presence of DHβE plus α-BGT nicotine did not modify the probability of successes. B, in low P (< 0.25) synapses nicotine-induced changes in the number of successes (to the first pulse) obtained in the presence DHβE (1 μm, white column) or α-BGT (100 nm, grey column) are normalized to the control values (dashed line). Note that in low P synapses the potentiating effect of nicotine was mediated by α7 receptor subtypes. *p < 0.05.

Time course of the amplitude of the first EPSC (filled circles) evoked in normal (2 mm calcium, 1.3 mm magnesium) and after switching to a low calcium containing solution (1 mm calcium, 2 mm magnesium, open bar). Note increase in failure rate and depression of EPSC amplitude in low Ca²⁺ (see average traces in the insets). Further application of nicotine (filled bar) produced a persistent increase in success rate and in EPSC amplitude (see insets). B, average time course of the effects of nicotine (filled bar) on EPSCs amplitude (normalized to their controls, dashed line) before and after switching to a low calcium-containing solution (open bar). Each bin is 1 min (n = 7). C, each column represents nicotine-induced changes in amplitude (including failures), successes rate, PPR, and CV, normalized to the pre-nicotine low extracellular Ca²⁺ concentration condition (dashed line; n = 7). D, time course of the amplitude of the first EPSC (filled circles) evoked in normal calcium and after switching to a high calcium-containing solution (4 mm calcium, 1 mm magnesium, open bar). Note decrease in failure rate and increase in EPSC amplitude in high Ca²⁺ (see average traces in the insets). Further application of nicotine (filled bar) produced a persistent decrease in success rate and in EPSC amplitude (see insets). E, average time course of the effects of nicotine (filled bar) on EPSCs amplitude (normalized to their controls, dashed line) before and after switching to a high calcium-containing solution (open bar). Each bin is 1 min (n = 5). F, each column represents nicotine-induced changes in amplitude (including failures), successes rate, PPR, and CV, normalized to pre-nicotine high extracellular Ca²⁺ concentration condition (dashed line; n = 5). *p < 0.05; **p < 0.01.

A, mean amplitude of field EPSPs (normalized to control, dashed line) recorded before and after nicotine application (bar). Each point represents the average of 6 responses evoked every 10 s in 10 different slices. B, mean amplitude of the afferent volley of the first field EPSP, recorded before (control, white column) and after nicotine application (grey column; n = 3). C, mean amplitude of field EPSPs (normalized to control, dashed line) recorded before and after nicotine application (bar) in the presence of α-BGT (100 nm) from the 12 slices in which nicotine was effective. Note that nicotine induced a significant depression in the amplitude of the field EPSP (p < 0.01). Insets above the graphs represent average traces (n = 100) from a representative slice recorded before (left) and 20 min after nicotine application (right). D, mean amplitude of the afferent volley of the first field EPSP, recorded before and after nicotine application (n = 5) in the presence of α-BGT.