https://speakerdeck.com/jonathanmwerner 2026-05-04 10:33:00 -0400 Wed, 08 Jul 2026 00:00:00 -0400 https://speakerdeck.com/jonathanmwerner/deleakage-preprint-journal-club-slides https://speakerdeck.com/jonathanmwerner/deleakage-preprint-journal-club-slides Neuropsychiatric disorders are associated with dysfunction across diverse neural circuits, complicating the identification of causal mechanisms and the development of targeted therapeutics. The habenula, a component of the epithalamus, has emerged as a particularly compelling structure in this context, serving as a key hub of reward circuitry that relays forebrain and limbic inputs to midbrain and brainstem systems, thereby influencing dopaminergic, serotonergic, and noradrenergic signaling. The habenula functions as an anti-reward system activated by negative outcomes and aversive states such as stress and drug withdrawal. Consistent with this role, habenula dysfunction has been implicated in multiple neuropsychiatric disorders, including schizophrenia, addiction, and depression; and modulation of habenula activity is associated with antidepressant response. Together, its central position in reward circuitry, broad disease associations, and therapeutic tractability support the habenula as a convergent node for neuropsychiatric risk and treatment. Despite this importance, the human habenula remains poorly characterized due to its small size and midline location, which limit its accessibility in post-mortem studies. Here, we generate a multi-modal atlas of the healthy adult human habenula from 10 neurotypical donors using single-nucleus RNA and chromatin accessibility profiling coupled with spatial transcriptomics (n=5). We define the cellular composition of the medial and lateral habenula, map these populations to their spatial context, and evaluate the enrichment of neuropsychiatric disease risk genes across cell types and spatial domains. Together, this work establishes a foundational resource of human habenula cell types and advances our understanding of the cellular, spatial, and regulatory landscape of a key hub in reward circuitry implicated in diverse neuropsychiatric disorders. Neuropsychiatric disorders are associated with dysfunction across diverse neural circuits, complicating the identification of causal mechanisms and the development of targeted therapeutics. The habenula, a component of the epithalamus, has emerged as a particularly compelling structure in this context, serving as a key hub of reward circuitry that relays forebrain and limbic inputs to midbrain and brainstem systems, thereby influencing dopaminergic, serotonergic, and noradrenergic signaling. The habenula functions as an anti-reward system activated by negative outcomes and aversive states such as stress and drug withdrawal. Consistent with this role, habenula dysfunction has been implicated in multiple neuropsychiatric disorders, including schizophrenia, addiction, and depression; and modulation of habenula activity is associated with antidepressant response. Together, its central position in reward circuitry, broad disease associations, and therapeutic tractability support the habenula as a convergent node for neuropsychiatric risk and treatment. Despite this importance, the human habenula remains poorly characterized due to its small size and midline location, which limit its accessibility in post-mortem studies. Here, we generate a multi-modal atlas of the healthy adult human habenula from 10 neurotypical donors using single-nucleus RNA and chromatin accessibility profiling coupled with spatial transcriptomics (n=5). We define the cellular composition of the medial and lateral habenula, map these populations to their spatial context, and evaluate the enrichment of neuropsychiatric disease risk genes across cell types and spatial domains. Together, this work establishes a foundational resource of human habenula cell types and advances our understanding of the cellular, spatial, and regulatory landscape of a key hub in reward circuitry implicated in diverse neuropsychiatric disorders. Mon, 04 May 2026 00:00:00 -0400 https://speakerdeck.com/jonathanmwerner/mapping-the-spatial-architecture-and-psychiatric-risk-landscape-of-the-human-habenula-at-cellular-resolution https://speakerdeck.com/jonathanmwerner/mapping-the-spatial-architecture-and-psychiatric-risk-landscape-of-the-human-habenula-at-cellular-resolution