Fig 2: Diverse LGE embryonic progenitor pools generate both dSPNs and iSPNs found intermixed in medial striatum(A) IUE of Ta1-Cre and FLEx reporter plasmids labeled Ta1-expressing (Ta1+/GFP+) and non-Ta1-expressing (Ta1-/ TdTom+) LGE progenitors.(B) Ta1+/GFP+ progenitors formed a large population during later embryonic stages.(C) Ta1+/GFP+ progenitors returned to a mitotic phase (M) earlier than Ta1-/TdTom+ progenitors (at 20 h post E15.5 IUE; Ta1+/GFP+: 4.98% ± 2.11% and Ta1-/TdTom+: 15.81% ± 3.63%, t test, p = 0.036, n = 418/8). pH3 was used as a mitotic marker.(D) Mitotic Ta1+/GFP+ progenitors at the ventricle often had a rounded morphology lacking a basal process.(E) In contrast, many mitotic Ta1-/TdTom+ progenitors at the ventricle retained a basal process during division.(F) The postnatal (P21–P35) striatum of IUE mice contained both aIP- and OP-derived neurons with spiny dendrites (top, right) and expressed molecular markers characteristic of striatal SPNs (bottom, left). aIP- and OP-derived neurons were found both in MOR+ patches (red) and MOR- matrix compartments (bottom right).(G) Relative numbers of aIP- and OP-derived neurons reflected the embryonic ratio of progenitors and were found in equal numbers within MOR+ patches.(H) Virtually all aIP- and OP-derived neurons expressed the SPN markers CTIP2 and DARPP-32 and consisted of both PPE-/dSPNs and PPE+/iSPNs.(I) Labeling for the markers DARPP-32 and CR (left) or PV and NPY (right).(J) Little to no co-expression was seen in aIP- or OP-derived neurons with interneuronal markers PV, NPY, or CR.(K) aIP- and OP-derived SPNs were found throughout striatum with on average a significant medial bias. Representative distribution of aIP- and OP-derived SPNs in an IUE brain (left). Scatterplot of dorsoventral and mediolateral position of all labeled SPNs (middle) and aIP- and OP-derived SPNs (right). Data are represented as mean ± SEM.

Fig 3: Adult ebGABAs display distinct anatomical and electrophysiological properties.a Quantification of the expression of single molecular markers in CA1 ebGABA. SOM: n = 4 mice; PV: n = 5 mice; NPY: n = 5 mice; M2R: n = 3 mice; nNOS weak/strong: n = 5 mice. Bar plots represent means. Error bars represent SDs. b Example ebGABA in stratum oriens expressing SOM and strong levels of nNOS (arrow). Note that neurons expressing weak levels of nNOS (arrowheads) are SOM immunonegative. Experiment repeated independently in four mice with similar results. c EbGABA in stratum radiatum expressing only M2R but not nNOS (arrow). Experiment repeated independently in three mice, obtaining similar results. d Neurolucida reconstructions of representative neurobiotin-filled ebGABA in the adult CA1. Axon is depicted in green. Soma and dendrites are colored in magenta. Inset: zoomed out representation to illustrate the rostro-caudal and dorso-ventral position. e Representative responses to +20, +520, and +820 pA current injections in ctrlGABA and ebGABA. Note the lower firing rate of the ebGABA in response to stronger current injections. f Top, f/I plot showing reduced excitability of ebGABA with strong current injections. Effect of current injection F(14,864) = 31.59, P < 0.0001; effect of birth date F(7,864) = 16.40, P < 0.0001, interaction F(98, 864) = 1.881 P < 0.0001, two-way ANOVA with Bonferroni post hoc test. Bottom, f/I plot limited to the first 50 ms of the current injection. Effect of current injection F(14,461) = 77.8, P < 0.0001; effect of birth date F(1,461) = 3.211, P = 0.0738, interaction F(1,461) = 1.676, P = 0.0573, two-way ANOVA with Bonferroni multiple comparisons test. CtrlGABAs: n = 18; ebGABAs: n = 16. Data are represented as means ± standard errors of the means. g Representative sag response of a ctrlGABA (black trace, −500 pA current injection) and an ebGABA (green trace, −250 pA current injection). Each trace is an average of three sweeps. h EbGABAs (n = 16 cells) display a significantly higher sag ratio (i.e., a lower sag amplitude) than ctrlGABAs (n = 18 cells, P = 0.028, two-sided Mann–Whitney U test). Boxplots represent medians (center), interquartile ranges (bounds), minima and maxima (whiskers). *P < 0.05; **P < 0.01; ***P < 0.001. so stratum oriens, sp stratum pyramidale, sr stratum radiatum, slm stratum lacunosum-moleculare. Source data are provided as a Source Data file.

Fig 4: Decrease in CRc density induce long-lasting defects in upper layer interneuron distribution(A) Confocal images of coronal sections in the barrel cortex (S1bf) of P25 controls, animals that were postnatally WP and ?Np73cre/+;R26dt-a/+ mutants, immunostained for markers of POA/CGE-derived interneurons Calretinin, Reelin, and NPY.(B) Quantifications of interneuron density in upper cortical layers (L1–3), layer 4 and deep cortical layers (L5–6) (Calretinin: n = 6 for controls, n = 4 for WP, n = 4 for ?Np73cre/+;R26dt-a/+; Reelin: n = 4 for controls, n = 6 for WP, n = 4 for ?Np73cre/+;R26dt-a/+; NPY: n = 4 for controls, n = 4 for WP, n = 4 for ?Np73cre/+;R26dt-a/+).(C) Quantification of interneuron density in upper cortical layers, L1 versus L2–3 (Calretinin: n = 6 for controls, n = 4 for WP, n = 4 for ?Np73cre/+;R26dt-a/+; Reelin: n = 4 for controls, n = 6 for WP, n = 4 for ?Np73cre/+;R26dt-a/+; NPY: n = 4 for controls, n = 4 for WP, n = 4 for ?Np73cre/+;R26dt-a/+).Values are expressed as means ± SEMs, 2-way ANOVA test with Dunnett’s multiple comparison correction. *p < 0.05; **p < 0.001; ***p < 0.0001. Scale bar represents 200 µm.

Fig 5: Effect of prematurity on interneurons density in BA9 of male infants. Illustrations of (A) glutamate decarboxylase 65 and 67 (GAD65-67, green), (B) SST (red), (C) CLB (red), (D) CRT (red), and (E) NPY (red) interneurons density. Scale bar = 20 µm. Quantification of (A’) GAD65-67, (B’) SST, (C’) CLB, (D’) CRT, and (E’) NPY positive cells in the upper layers (ULs), lower layers (LLs) and subcortical white matter (SWM) of the BA9 of the frontal cortex of term and preterm male infants. BA9 of female infants are presented on Extended Data Figure 1-1. Interneuron-related protein expression and transcripts are presented in Extended Data Figures 1-2, 1-3, respectively. Scatter dot plots represent the mean and individual dispersion of seven to nine term (empty circles) and six to seven preterm infants (full circles); *p < 0.05 (two-way ANOVAs were performed followed by Fisher’s LSD tests for post hoc comparisons).