Fig. 1. Caffeine-induced high-frequency synchronized oscillations in hippocampal CA3 region of chronic lead-exposed rats: (A) the fEPSPs recorded in the hippocampal area CA3 of rats exposure to lead with superfusion of normal ACSF; (B) the fEPSPs following application of ACSF containing 0.01 mM caffeine. Caffeine, 0.01 mM, could only induce 0.1 ± 0.07 mV oscillations which consist of two to three wavelets; (C) synchronized oscillations (1.0 ± 0.12 mV) elicited in the same slices by 0.1 mM caffeine.

Fig. 2. Caffeine-induced oscillations are reversible: (A) the synchronized oscillations after superfusion of ACSF with 0.1 mM caffeine; (B) 30 min later wash of normal ACSF, the caffeine-induced oscillations were significantly reduced; (C) the oscillations elicited by caffeine disappeared after normal ASCF wash for 60 min.

Fig. 3. Caffeine-induced oscillations in DG region of chronic lead-exposed rats. (A) The fEPSPs recorded in the hippocampal DG region of lead-exposed rats with superfusion of normal ACSF; (B) synchronized oscillations (0.2 ± 0.08 mV) were induced in 3 of 25 slices of DG.

Fig. 4. The effect of Mg²⁺ and Ca²⁺ on the oscillatory bursting elicited by caffeine: (A) fEPSPs recorded in the presence of normal ACSF; (B) oscillations recorded in the presence of ACSF containing 0.1 mM caffeine and 0.5 mM Mg²⁺, the average amplitude is 2.0 mV, and the duration is over 80 ms; (C) fEPSPs recording with [Mg²⁺]_o at 3 mM; (D) caffeine failed to induce synchronized oscillations in ACSF containing 3 mM [Mg²⁺]_o; (E) the synchronized oscillations were observed after washing for 30 min with normal ACSF; (F) the plot of normalized amplitude of oscillations against time (minutes) course during the whole period of application of 5 mM EGTA; (G) voltage-dependent calcium channels blocker Cd²⁺ (100 μM), T-type calcium channel antagonist Ni²⁺ (100 μM), and L-type calcium channel antagonist nicardipine (10 μM) have no effect on synchronized oscillations induced by caffeine.

Fig. 5. Caffeine-induced synchronized oscillations are insensitive to GABA_A receptors antagonists and several types of calcium channel blockers: (A) the fEPSPs recorded in hippocampal CA3 region of chronic lead-exposed rats with superfusion of normal ASCF; (B) synchronized oscillations are induced with the application of bicuculline (10 μM) and 0.1 mM caffeine. Bicuculline has no effect on frequency and amplitude of caffeine-induced synchronized oscillations.

Fig. 6. AP-5 blocked the bursting of caffeine-induced oscillations: (A) with superfusion of ACSF containing 0.1 mM caffeine together with 50 μM AP-5, an antagonist of NMDA receptors, AP-5 completely blocked the bursting of oscillations induced by caffeine; (B) washout of ASCF with 0.1 mM caffeine, 10–15 min later, the caffeine-induced oscillations were observed; (C) normalized amplitude of caffeine-induced oscillations is plotted against time (minutes) course.

Fig. 7. Dependence of caffeine-induced oscillations on AMPA receptors activity: before (A) and after (B) application CNQX (20 μM), an AMPA receptors antagonist. (C) The bath application of CNQX, the caffeine-induced oscillations were partially recovered after 12–15 min; (D) normalized mean oscillatory amplitude is plotted against time course during the whole period of application of CNQX.