ArticleBiological psychiatry global open science2023
Single-Nucleus Transcriptional Profiling of GAD2-Positive Neurons From Mouse Lateral Habenula Reveals Distinct Expression of Neurotransmission- and Depression-Related Genes.
Article in Biological psychiatry global open science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- Opioid withdrawal engages a habenular subpopulation responsive to aversive states.bioRxiv : the preprint server for biology · 2026Article
- The lateral habenula as a master regulator of innate and learned social behaviors.Psychopharmacology · 2026Review
- The Somatostatin Pathway Projected from the Basal Forebrain to the Lateral Habenula Promotes Isoflurane Anesthesia Recovery.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Analysis of a shark reveals ancient, Wnt-dependent, habenular asymmetries in vertebrates.Nature communications · 2024Article
- Antibody-assisted selective isolation of Purkinje cell nuclei from mouse cerebellar tissue.Cell reports methods · 2024Article
- Whole-brain connections of glutamatergic neurons in the mouse lateral habenula in both sexes.Biology of sex differences · 2024Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Background: Glutamatergic projection neurons of the lateral habenula (LHb) drive behavioral state modulation by regulating the activity of midbrain monoaminergic neurons. Identifying circuit mechanisms that modulate LHb output is of interest for understanding control of motivated behaviors. Methods: A small population of neurons within the medial subnucleus of the mouse LHb express the GABAergic (gamma-aminobutyric acidergic)-synthesizing enzyme GAD2, and they can inhibit nearby LHb projection neurons; however, these neurons lack markers of classic inhibitory interneurons, and they coexpress the vesicular glutamate transporter VGLUT2. To determine the molecular phenotype of these neurons, we genetically tagged the nuclei of GAD2-positive cells and used fluorescence-activated nuclear sorting to isolate and enrich these nuclei for single-nucleus RNA sequencing. Results: Our data confirm that GAD2+/VGLUT2+ neurons intrinsic to the LHb coexpress markers of both glutamatergic and GABAergic transmission and that they are transcriptionally distinct from either GABAergic interneurons or habenular glutamatergic neurons. We identify gene expression programs within these cells that show sex-specific differences in expression and that are implicated in major depressive disorder, which has been linked to LHb hyperactivity. Finally, we identify the Conclusions: These data show the value of using genetic enrichment of rare cell types for transcriptome studies, and they advance understanding of the molecular composition of a functionally important class of GAD2+ neurons in the LHb.
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Registered trials
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