Kisspeptin neurons in the mediobasal hypothalamus (MBH) are critical targets of ovarian estrogen feedback regulating mammalian fertility. To reveal molecular mechanisms underlying this signaling, we thoroughly characterized the estrogen-regulated transcriptome of kisspeptin cells from ovariectomized transgenic mice substituted with 17β-estradiol or vehicle. MBH kisspeptin neurons were harvested using laser-capture microdissection, pooled, and subjected to RNA sequencing. Estrogen treatment significantly ( p.adj . < 0.05) up-regulated 1,190 and down-regulated 1,139 transcripts, including transcription factors, neuropeptides, ribosomal and mitochondrial proteins, ion channels, transporters, receptors, and regulatory RNAs. Reduced expression of the excitatory serotonin receptor-4 transcript ( Htr4 ) diminished kisspeptin neuron responsiveness to serotonergic stimulation. Many estrogen-regulated transcripts have been implicated in puberty/fertility disorders. Patients ( n = 337) with congenital hypogonadotropic hypogonadism (CHH) showed enrichment of rare variants in putative CHH-candidate genes (e.g., LRP1B , CACNA1G , FNDC3A ). Comprehensive characterization of the estrogen-dependent kisspeptin neuron transcriptome sheds light on the molecular mechanisms of ovary–brain communication and informs genetic research on human fertility disorders.

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Excessive fear learning and extinction-resistant fear memories are core symptoms of anxiety and trauma-related disorders. Despite significant evidence from clinical studies reporting hyperactivity of the bed nucleus of stria terminalis (BNST) under these conditions, the role of BNST in fear learning and expression is still not clarified. Here, we tested how BNST modulates fear learning in mice using a chemogenetic approach. Activation of GABAergic neurons of BNST during fear acquisition, more specifically the consolidation phase, resulted in enhanced cued fear recall. Importantly, BNST activation had no acute impact on fear expression during conditioning or recalls, but it enhanced cued fear recall subsequently, potentially via altered activity of downstream regions as indicated by c-Fos. Enhanced fear memory consolidation could be replicated by selectively activating somatostatin neurons (but not corticotropin releasing factor neurons), suggesting significant modulation of fear memory strength by specific circuits of BNST.