Fig. 1: PCP induces GABA expression in PL glutamatergic neurons and suppressing this GABA expression prevents PCP-induced locomotor sensitization and cognitive deficits.

a Experimental protocol. Cartoon after⁷⁵. b PL neurons co-expressing mCherry and GABA (arrowheads). Scale bar, 25 μm. c Quantification of GABA⁺/mCherry⁺ and GAD67⁺/mCherry⁺ neurons (n = 5 mice). d PL locations of glutamatergic neurons that co-expressed GAD1 or changed transmitter identity upon treatment with PCP. Cartoons were produced by superimposing the locations of neurons in three PL sections, each from a different mouse, all positioned at Bregma 1.94. Different shapes represent cells from different mice. e, f Expression of VGAT and VGLUT1 mRNA puncta in PL neurons of PCP-treated mice. Scale bar, 20 μm. g, h Quantification of VGAT and VGLUT1 expression measured as percent of cell area occupied by mRNA puncta across PL neuronal subtypes (n = 25 cells/type/mouse for 3 mice). i Experimental protocol. Cartoon after⁷⁵. j Expression of shGAD1-GFP in the PL. Scale bar, 500 μm. k Quantification of neurons co-expressing VGLUT1 and GAD1 transcripts in AAV-injected mice (n = 4 mice). l–n shGAD1 prevents PCP-induced deficits in locomotor sensitization (l, n= from left to right 10, 10, 8, 10 mice), in the Novel Object Recognition Test (NORT) (m, n= from left to right 8, 8, 6, 9 mice) and Spontaneous Alternation Task (SAT) (n, n= from left to right 10, 8, 6, 10 mice). o–q The number of PL GAD1⁺/VGLUT1⁺ neurons is positively correlated with locomotor sensitization and negatively correlated with performance in the NORT and SAT (n = 4 mice). Statistical significance (**P < 0.01, ***P < 0.001, ****P < 0.0001) was assessed using two-sided unpaired t-test (c), Kruskal–Wallis followed by Dunn’s test (g, h), two-way ANOVA followed by Tukey’s test (k–n), and two-sided linear regression and Pearson’s correlation analysis (o–q). Data are presented as mean ± SEM. The exact p-values and additional statistical details can be found in Supplementary Table 1.