Dual midbrain and forebrain origins of thalamic inhibitory interneurons

The proportion and distribution of local inhibitory neurons (interneurons) in the thalamus varies widely across mammals. The ubiquitous presence of interneurons in the thalamus of primates contrasts with the extreme sparsity of interneurons reported in mice and other small-brained mammals. This is reflected in the structure and function of thalamic local circuits, which are more complex in primates compared to rodents. To what extent the broad range of interneuron densities observed in mammalian species reflect the appearance of novel interneuron types or the elaboration of a plesiomorphic ontogenetic program, remains unclear. Here, we identify a larger than expected complexity and distribution of interneurons across the mouse thalamus, where all thalamic interneurons can be traced back to two developmental programs: one specified in the midbrain and the other in the forebrain. Interneurons migrate to functionally distinct thalamocortical nuclei depending on their origin the abundant, midbrain-derived class populates the first and higher order sensory thalamus while the rarer, forebrain-generated class is restricted to some higher order associative regions. We also observe that markers for the midbrain-born class are abundantly expressed throughout the thalamus of the New World monkey marmoset. These data therefore reveal that, despite the broad variability in interneuron density across mammalian species, the blueprint of the ontogenetic organization of thalamic interneurons of larger-brained mammals exists and can be studied in mice. ### Competing Interest Statement The authors have declared no competing interest.