The habenula (Hb) plays a key role in processing reward information and mediating aversive responses to negative stimuli. In the recent issue of Cell Reports, Lieke van de Haar and colleagues have revealed how the cellular diversity of the mouse habenula is formed during development. In the work title “Cellular diversity of developing habenula may illuminate risk for human psychiatric disorders”, Lieke used single cell RNA sequencing, a technique that allows quantification of gene expression in thousands of cells simultaneously.
Reconstruction of lineage trajectories using computational tools revealed paths to habenula cell types. Intersectional genetics experiments by Oxana Garritsen showed that these include a physiologically distinct neuronal cell type that innervate the dorsal IPN which can be identified by Cartpt expression. Work by Lieke and Youri Adolfs using iDISCO and light sheet microscopy have shown that these cells localize to the medial habenula. The ePhys work by Danai Riga of the Meye lab found that these Cartpt+ neurons are electrophysiologically different from surrounding neurons. Finally, MAGMA analysis by Juliska Boer, who did her bachelor internship under the supervision of Lieke, revealed that developing cell populations align with human genetic risk loci of psychiatric disorders, such as the major depressive disorder.
“The habenula plays an important role in negative experiences, and is located dorsally to the thalamus and ventrally to the hippocampus…. we were interested in how the cells of the habenula are born and mature.” Lieke
Lieke performed her PhD work at the Pasterkamp lab of our Translational neuroscience department of the UMC Utrecht Brain Center. This work is a fine example of internal collaborations in the department which connect molecular, computational, genetic and electrophysiological techniques.