Figure 5. Both Voluntary Running and Elevating RGS6 Expression Levels in Adult-born Neurons Reduces Their Sensitivity to GABA_B Receptor-Mediated inhibition.

(A) Hypothetic model for the role of RGS6 in reduced sensitivity to GABA_B receptor signaling in running mice. GABA_B receptor activation by GABA or baclofen leads to activation of Gα and dissociation of Gβγ subunits from trimeric G protein complex. Gβγ is inhibitory to voltage-gated calcium channel (VGCC) in adult new neurons. Elevated RGS6 accelerates GTP hydrolysis therefore terminates GABA_B receptor activation and relieves the inhibitory effects on VGCC, rendering adult new neurons less sensitive to GABA or baclofen-activated GABA_B signaling.

(B) Experimental timeline for testing the efficiency of the GABA_B agonist baclofen on suppression of Ca²⁺ currents in immature GCs in sedentary and running mice.

(C-D) Average traces (left) of baclofen-induced (30 μM, red) suppression of peak Ca²⁺ currents recorded in immature neurons from sedentary (C) and running (D) mice. In sedentary mice (C, right), baclofen reduced the peak current from 11.7 ± 2.3 pA/pF to 4.6 ± 0.9 pA/pF (n=5, P=0.01, paired t-test), whereas baclofen had no significant effect on currents in running mice (15.1 ± 7 pA/pF to 14.5 ± 8.6 pA/pF, n=6, P=0.8, paired t-test)(D, right).

(E) Experimental timeline for testing the efficiency of baclofen on suppression of Ca2+ currents in immature GCs in GFP (GFP only Control) and RGS6 OE (RGS6 overexpression) mice.

(F-G) Left, examples of baclofen-induced (30 μM, red) suppression of peak Ca²⁺ currents recorded from control GFP immature GCs (F) or RGS6 OE immature GCs (G). Right, in control GFP immature GCs baclofen reduced the peak Ca²⁺ current from 20.7 ± 1.7 pA/pF to 15.2 ± 1.7 (n=6, P<0.001, paired t-test). In RGS6 OE immature GCs baclofen did not affect Ca²⁺ currents (18.6 ± 1.4 to 18.8 ± 1.5, n=6, P=0.7).