Behavioral inflexibility through overtraining is mediated by reduced mGluR1/5 signaling capacity in the dorsolateral striatum
Fig 1
DLS mGluR1/5 signaling activation in instrumental conditioning and differential behavioral sensitivity to A–O changes with training duration.
(A, D) Schematic of behavioral regimes followed by protein analysis, and targeted intracellular signaling cascades. (B) Active nose-poke (ANP) rates (ANP/min) during training of instrumental conditioning for food reward (T_Veh/T_DHPG n = 8). (C) Representative western blots of pAkt, Akt, and Calnexin (loading control) in response to in vivo infusion of vehicle or DHPG (i.c., 9 ng/0.5 µl) into the DLS. Plots represent quantified data groups of pAkt/Akt (T_VehpAkt/Akt, 1.00 ± 0.12, n = 8; T_DHPGpAkt/Akt, 1.21 ± 0.11, n = 8; T_VehpAkt/Akt vs. T_DHPGpAkt/Akt paired t test, **p = 0.01, t = 3.41, dF = 7). (E) ANP rates during training in the two experimental groups (T n = 9; T_S n = 9). (F) Representative western blots of pAkt, Akt, and Calnexin in response to an additional VI-60 session performed 24 h after the end of the training. Bar graphs show expression level ratios (relative to T) of pAkt/Akt (TpAkt/Akt: 1.00 ± 0.07, n = 9; T_SpAkt/Ak: 1.57 ± 0.11, n = 9; TpAkt/Akt vs. T_SpAkt/Akt unpaired t test, ***p = 0.0006, t = 4.29, dF = 16). (G) Schematic of the short and overtraining regimes, followed by post-training procedures. (H) ANP rates during instrumental learning in short- (Sh, n = 19) and overtrained mice (Ov, n = 16). (I) Post-training omission procedure. (Left) Comparison of ANP rates between positive and negative A–O contingency in both short- and overtrained mice (Sh n = 10, positive A–O: 9.4 ± 1.2, negative A–O: 5.2 ± 1.1, Sidak ***p = 0.001; Ov n = 8, positive A–O: 10.8 ± 1.4, negative A–O 10.4 ± 1.9; Sidak p = 0.9). (Right) Time courses of ANP ratios (ANP rates under negative A–O/ANP rates under positive A–O) in short- and overtrained mice. (J) Post-training devaluation procedure in short- and overtrained mice (Sh n = 9, Ov n = 8). ANP rates in the valued and devalued conditions (Sh, valued: 6.0 ± 1.1; devalued 2.2 ± 0.5, Sidak **p = 0.001; Ov, valued: 4.1 ± 0.47, devalued: 5.5 ± 0.76, Sidak p = 0.32). (B, E, F, H, I) Data are presented mean ± standard error of the mean (SEM). Data set are available at the following link: https://doi.org/10.48557/VCAWUD.