Figure 3.

Imipramine and fluoxetine decrease GABA neurotransmission from a specific hippocampal inhibitory circuit. A, Polysynaptic IPSC responses to Schaffer collateral stimulations (inset). Neurons were held at the reversal potential of glutamate-mediated responses; hence the lack of inward excitatory currents. Polysynaptic IPSCs relied on glutamatergic transmission as they were blocked by the glutamate receptor antagonist DNQX (10 μm). Gray traces, overlapped single-sweep responses. Black trace, six-sweep average trace. B, A polysynaptic IPSC (black line) was fitted using the sum (green line) of two double-exponential functions (dashed lines) for early and late peaks. C–E, Imipramine (IMI, 20 μm; C, light gray trace) and fluoxetine (FLUO, 20 μm; D, light gray trace) diminished the early component of the composite IPSCs (blue lines), whereas the synthetic cannabinoid WIN 55212-2 (WIN, 1 μm; E, gray trace) reduced the late components (red lines) of the polysynaptic inhibitory response. Solid and dashed blue and red lines refer to the fitted exponentials before (solid) and after (dashed) drug application. Arrowheads in A–E indicate the extracellular stimulus, whose artifacts were digitally removed. F, Population data showing early (1) and late (2) IPSC peaks for individual neurons in control (C), imipramine (I), fluoxetine (F), and WIN (W). Data are plotted in logarithmic scale. *p < 0.05; **p < 0.01.