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. 2007 Jan 10;27(2):341–354. doi: 10.1523/JNEUROSCI.4051-06.2007

Figure 1.

Figure 1.

Folimycin treatment induces frequency-dependent depression of synaptic responses at excitatory synapses in the CA1 region of hippocampal slices. A–E, Blockade of vesicle refilling evaluated by synaptic depression at 0.1 (A), 1 (B), 10 (C), 20 (D), and 30 Hz (E) electrical stimulation after 10 min of folimycin exposure. Folimycin treatment hastened synaptic depression at excitatory synapses in higher frequencies with an early onset. Insets show the first and last 5 AP-evoked EPSCs at 0.1 and 1 Hz, and the first and last 10 responses for 10, 20, and 30 Hz of continuous stimulation from individual recordings (the top trace for each experimental protocol represents controls and the bottom trace folimycin-treated cells). Folimycin-treated slices respond to stimulation with a continuous decline in neurotransmitter release with a faster rate of depression than that recorded in controls (p < 0.05; n = 5–7 cells for each experimental protocol and group). The decline was more prominent at higher frequencies in the folimycin-treated group. F, Bar graphs and representative traces of the average amplitude of the first evoked responses to the stimulation trains. There was a small but statistically insignificant decrease in the amplitudes of the first evoked responses recorded from folimycin-treated cells. Data shown are mean ± SEM. G, H, Synaptic depression shows a dramatic frequency dependent increase at frequencies >1 Hz, regardless of the number of action potentials applied. Plots show depression induced by 1, 10, 20, and 30 Hz stimulation frequencies applied for 200 pulses at pharmacologically isolated excitatory synapses (G) and after folimycin treatment (H). Plots were prepared from the data presented in A–E. At 0.1 and 1 Hz, fast time constants of synaptic depression from vehicle-treated slices were 303.1 ± 22.9 and 180.1 ± 48.4 s, respectively. At these frequencies, the time constants from folimycin-treated slices were comparable (276.8 ± 27.5 and 165.8 ± 31.3 s, respectively; p > 0. 50 for each frequency) with controls. At 10, 20, and 30 Hz, the time constants of synaptic depression were faster at folimycin-treated excitatory synapses compared with controls (at 10, 20, and 30 Hz stimulation, the time constants, respectively, were 2.1 ± 0.3, 1.7 ± 0.1, and 1.1 ± 0.2 s for controls, and 1.33 ± 0.1, 1.1 ± 0.1, and 0.7 ± 0.1 s for folimycin-treated synapses; p < 0.05 for all; n = 5–7 cells).