Figure 2.

Effects of THP on CA1 hippocampal pyramidal cells at puberty. At the onset of puberty, THP reduces the tonic GABAergic current and increases excitability of CA1 pyramidal cells in the slice. (A) THP (30 nM) effects on the tonic current recorded with gramicidin perforated patch techniques to maintain the internal Cl⁻ milieu. 1 μ M TTX, 1 μ M GABA, and 2 mM kynurenic acid were added to isolate the GABAergic post-synaptic component. L-655, 708, CGP55845, and TEA were also added to block α5 and GABA_B receptors and K+ channels, respectively. Pre-pub, pre-pubertal; Pub, pubertal; GBZ, gabazine, a GABA antagonist (presented for comparison). THP reduces the current in Pub slices. (Representative of 5 cells/group) (B) Left panel, Hyperpolarizing current recorded from CA1 hippocampal pyramidal cells in the slice using whole cell patch clamp techniques (ECl = −70 mV, −50 mV holding potential; pipette solution, K-gluconate; bath, 200 nM gabazine to block synaptic current and 2 mM kynurenic acid to block excitatory current). Right panel, effects of THP on the depolarizing tonic current at puberty (ECl = −30 mV, pipet solution, CsCl). THP reduces hyperpolarizing current in wild-type but not δ^−/− mice, but potentiates depolarizing current. (Representative of 8–12 cells/group) (C) Whole-cell current-clamp recordings reveal voltage responses recorded in response to increasing 0.3-nA current injection (initial current −1 nA). (The THP trace lacks the 800-pA current trace for ease of comparison.) THP lowers the current threshold for spiking of pyramidal cells at the onset of puberty in wild-type but not δ^−/− mice. Red trace, equivalent current injection, threshold for the less excitable state. Blue trace, equivalent current injection, threshold for the more excitable state. (Representative of 7–8 cells/group) [Revised and used with permission (Shen et al., 2007)].