Journal: Molecular psychiatry

Article Title: Dichotomous Regulation of Striatal Plasticity by Dynorphin

doi: 10.1038/s41380-022-01885-0

Figure Lengend Snippet: A Summary plot showing enhanced LTP in the presence of D1 agonist (SKF81297) recorded from WT (D1-cre;pDyn+/+)mice. The solid line shows LTP recorded without SKF81297 for reference (same as Figure 1B). B Summary plot showing enhanced LTP in the presence of D1 agonist (SKF81297) recorded from D1-pDyn cKO (D1-cre;pDynfl/fl)mice. SKF81297 did not further enhance LTP in D1-pDyn cKO mice. The solid line shows LTP recorded from D1-pDyn cKO mice without SKF81297 for reference (Same as Figure 3A). C Summary plot showing enhanced LTP in the presence of D1 agonist (SKF81297) and KOR antagonist (U50488) recorded from WT (D1-cre;pDyn+/+) mice. In the presence of SKF81297, U50488 failed to block the LTP. The solid line shows recording in the presence of +U50488 alone for reference (Same as Figure 1D). D Box-plot summary showing LTP levels in the presence of SKF81297. WT+SKF, n = 7/3, 206.76% ± 24.5; cKO+SKF, n = 7/3, 211.83% ± 19.76; WT+U488+SKF, n = 7/2, 210.82% ± 29.05. WT+SKF vs cKO+SKF, p = 0.805; WT+SKF vs WT+U488+SKF, p = 0.71; cKO+SKF vs WT+U488+SKF, p = 0.99, Mann-Whitney. E The schematic depicting the signaling pathway of D1R and KOR activation. D1R activation enhanced dSPN LTP expression regardless of whether Dyn/KOR pathway is activated. F Summary plot showing the same STDP induction protocol resulted in LTD in the presence of D1R antagonist (SCH23390) recorded from WT (D1-cre;pDyn+/+) mice. The solid line shows control LTP for reference. G Summary plot showing LTP is dampened to WT control LTP level in the presence of D1 antagonist (SCH23390) recorded from D1-pDyn cKO (D1-cre;pDynfl/fl) mice. The solid red line shows LTP in cKO mice and solid black line shows WT control LTP for reference. H Summary plot showing LTP recorded from WT (D1-cre;pDyn+/+) mice in the presence of both D1 antagonist (SCH23390) and KOR antagonist (norBNI). When D1R is blocked, blocking KOR resulted in normal LTP. The solid orange line shows WT+norBNI LTP and solid black line shows control LTP for reference. I Box-plot summary showing LTP levels in the presence of D1R antagonist (SCH23390). Loss of KOR function rescued LTP in the presence of D1R antagonist. WT+SCH, n = 9/4, 59.95% ± 11.72; cKO+SCH, n = 9/3, 156.01% ± 19.31; WT+norBNI+SCH, n = 9/4, 154.68% ± 14.14. WT+SCH vs cKO+SCH, p = 0.0008; WT+SCH vs WT+norBNI+SCH, p = 0.0005; cKO+SCH vs WT+norBNI+SCH, p = 0.99, Mann-Whitney. J The schematic depicting the signaling pathway of D1R and KOR blockade. Blockade of D1R suppressed dSPN LTP, deletion or blockade of KOR rescued LTP in the presence of D1R antagonist. Data are presented as mean ± SEM. ns: not significant, p > 0.05, *** p < 0.001.

Article Snippet: Conversely, in the presence of the D1R antagonist SCH23390 (3 μM), dSPNs from WT D1-cre;pDyn +/+ mice expressed long-term depression (LTD) even though an LTP induction protocol was used ( ) and is consistent with previous findings ( 12 ).

Techniques: Blocking Assay, MANN-WHITNEY, Activation Assay, Expressing