Figure 5.

Stimulation of 5-HT₇R/G₁₂ signaling increases basal neuronal excitability and modulates synaptic plasticity. A, Basal synaptic transmission in 5-CT-treated and control organotypic preparations, as well as from in cultures from Gα₁₂-deficient mice (G₁₂KO) measured as a relationship between the stimulus strength and amplitude of fEPSP from the Schaffer collateral–CA1 synapses. Although the maximal responses obtained at high-stimulation intensities (100–150 μA) in the 5-CT-treated (n = 12) and control (n = 15) slices are similar, the mean fEPSP amplitude at low-stimulation strengths (10–40 μA) is significantly increased in 5-CT-treated preparations and decreased in organotypic cultures from Gα₁₂-deficient mice (n = 9). Data are presented as mean ± SEM. A statistically significant difference between values is indicated (*p < 0.05; **p < 0.01; ***p < 0.001). Representative recordings of fEPSPs performed at 50% of maximal response (20 μA) and at maximal intensities (140 μA) are shown for control, 5-CT-treated, and Gα₁₂ knock-out preparations on the right. B, Analysis of PPF in CA1 synapses from the control, 5-CT-treated, and Gα₁₂-deficient mice preparations. C, High-frequency stimulation (1 × 100 Hz for 1 s) of Schaffer collaterals in organotypic slices treated with 5-CT (n = 12) results in changed LTP of fEPSPs compared with control preparations (n = 15). Data shown are mean ± SEM of normalized fEPSPs. Representative recordings of fEPSPs performed at 50% of maximal response were evoked and recorded 5 min before (gray curves) and 50–60 min after (black curves) 1 × 100 Hz stimulation and are shown on the right for the control, 5-CT-treated, and Gα₁₂ knock-out preparations. Scale bars on the right show the corresponding amplitude increment. LTP was determined as maximal responses between 50 and 60 min after the high-frequency stimulation (n = 13; p < 0.01). KO, Knock-out.