COMPARATIVE ANALYSIS OF THE MOLECULAR, SPATIAL, AND FUNCTIONAL DOMAINS OF VERTEBRATE HABENULA

The habenula is an evolutionarily conserved diencephalic nucleus that is significant for neuropsychiatric disorders and adaptive behaviors. Two main habenula subdivisions, the lateral habenula and medial habenula, which have distinct roles in a variety of behaviors including operant and classical learning, outcome prediction, addiction, and social interactions. However, our understanding of cytoarchitecture and topography of the vertebrate habenula, and how its different microcircuits are organized across species, remains limited. Here, we utilized a combination of single-cell and spatial transcriptomic approaches across multiple species to investigate how habenular subdivisions are organized and how this organization compares across species. First, we identified numerous molecularly and spatially distinct habenular subdomains across species and found they are highly spatially organized. Second, although the zebrafish habenula is typically asymmetric between hemispheres, we showed several symmetrical subdomains, similar to those in the mouse habenula. Likewise, while the mouse habenula is accepted as symmetrical, we identified several significantly asymmetric subregions. Together, these findings suggest that asymmetry in the vertebrate habenula varies along a continuum among different species. Finally, we found that many habenular cell types are conserved across species, with some exceptions. We are currently analyzing two-photon recordings of spontaneous neural activity of adult zebrafish habenula, focusing on whether the activity patterns can be organized into functional clusters and how these clusters relate to habenular subdomains. This will help clarify how the molecular topography of the zebrafish habenula relates to its functional architecture, providing a framework for linking conserved cell-type organization to circuit-level function across vertebrate species.