Skip to main content
. Author manuscript; available in PMC: 2009 Sep 11.
Published in final edited form as: Biol Psychiatry. 2008 Jul 18;64(8):691–700. doi: 10.1016/j.biopsych.2008.06.003

Figure 6.

Figure 6

Decreased AKT signaling increases the excitability of ventral tegmental area (VTA) dopamine neurons. (A) Extracellular recordings from VTA dopamine neurons reveal that 100 μmol/L LY294002, an inhibitor of PI3K that reduces thymoma viral proto-oncogene (AKT) phosphorylation and activity (51), significantly increases spontaneous pacemaker firing frequency (t10 = 2.0, p < .05, n = 5–6, 3–4 mice/group, paired t test), which is reversed by washout (representative traces shown on right). SR95531, 2 μmol/L, (a γ-aminobutyric acid [GABA]A antagonist) also increases VTA firing frequency and blocks further LY294002 mediated increases in VTA excitability (n = 7/group). (B) In whole-cell voltage-clamp recording experiments, 100 μmol/L LY294002 also produced significant decrements in the amplitude (t6 = 3.09, p < .05) and frequency (t6 = 3.16, p < .05, n = 7 neurons/group, 3–4 mice/group, paired t tests) of spontaneous GABA-mediated inhibitory postsynaptic currents (IPSCs) onto VTA dopamine neurons (representative IPSC traces shown above). Data are shown as mean + SEM, with * and ** indicating significant (p < .05 or p < .01) paired t test comparisons against the control condition.