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Separation of interneurons from medial ganglionic eminence (MGE) and caudal ganglionic eminence (CGE) in control and TSC human frontal cortex. a Schematic overview illustrating the location of the MGE and CGE and their migration patterns during development. b Transcription factor analysis highlighting the expression pattern of factors associated with the MGE and CGE. Each row represents a specific transcription factor, and each column represents a distinct interneuron cluster. The color scale indicates the relative expression level, with higher expression shown as white or green. Clear distinctions can be observed, emphasizing the molecular differences between these two interneuron populations. c Unsupervised clustering heatmap illustrating the shared expression patterns of MGE- and CGE-derived interneuron subpopulations. The heatmap visually demonstrates the hierarchical clustering of samples based on shared transcriptional signatures. Clusters within the green boxes belong to the CGE-derived interneuron subpopulation. Purple indicates MGE-derived interneuron subpopulations and blue remains undetermined. (Clustering method = complete). d UMAP plot displaying the interneuron clusters segregated into CGE and MGE clusters. The separation of interneurons from the MGE and CGE is evident with only two clusters of which it is unsure what their origin is based on the original UMAP combined with the unsupervised clustering based on transcription factors

Separation of interneurons from medial ganglionic eminence (MGE) and caudal ganglionic eminence (CGE) in control and TSC human frontal cortex. a Schematic overview illustrating the location of the MGE and CGE and their migration patterns during development. b Transcription factor analysis highlighting the expression pattern of factors associated with the MGE and CGE. Each row represents a specific transcription factor, and each column represents a distinct interneuron cluster. The color scale indicates the relative expression level, with higher expression shown as white or green. Clear distinctions can be observed, emphasizing the molecular differences between these two interneuron populations. c Unsupervised clustering heatmap illustrating the shared expression patterns of MGE- and CGE-derived interneuron subpopulations. The heatmap visually demonstrates the hierarchical clustering of samples based on shared transcriptional signatures. Clusters within the green boxes belong to the CGE-derived interneuron subpopulation. Purple indicates MGE-derived interneuron subpopulations and blue remains undetermined. (Clustering method = complete). d UMAP plot displaying the interneuron clusters segregated into CGE and MGE clusters. The separation of interneurons from the MGE and CGE is evident with only two clusters of which it is unsure what their origin is based on the original UMAP combined with the unsupervised clustering based on transcription factors

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GABAergic interneurons play a critical role in maintaining neural circuit balance, excitation–inhibition regulation, and cognitive function modulation. In tuberous sclerosis complex (TSC), GABAergic neuron dysfunction contributes to disrupted network activity and associated neurological symptoms, assumingly in a cell type-specific manner. This GABA...