NDNF is selectively expressed by neocortical, but not habenular neurogliaform cells

The lateral habenula (LHb) is a brain structure which is known to be pathologically hyperactive in depression, whereby it shuts down the brains' reward systems. Interestingly, inhibition of the LHb has been shown to have an antidepressant effect, hence making the LHb a fascinating subject of study for developing novel antidepressant therapies. Despite this however, the exact mechanisms by which inhibitory signalling is processed within the LHb remain incompletely understood. Some studies have proposed the existence of locally targeting inhibitory interneuron populations within the LHb. One such population is believed to be akin to neocortical neurogliaform cells, yet specific molecular markers for studying these neurons are sparse and hence their function remains elusive. Recently, neuron-derived neurotrophic factor (NDNF) has been proposed as one such marker for neocortical neurogliaform cells. Using a combination of histological, physiological and optogenetic tools, we hence sought to first validate if NDNF was selectively expressed by such inhibitory neurons within the neocortex, and then if it was confined to a similar population within the LHb. While we report this to be true for the neocortex, we find no such evidence within the LHb; rather that NDNF is expressed without restriction to a particular neuronal subpopulation. These results hence indicate that molecular markers can represent broadly diverse populations of neurons on a region-to-region basis and that therefore each population as defined by molecular marker expression should be validated in each brain structure.

Automated summary

The lateral habenula (LHb) is pathologically hyperactive in depression and inhibiting it has been shown to have antidepressant effects. While there are proposed locally targeting inhibitory interneuron populations within the LHb, specific molecular markers for studying these neurons are sparse. Recent research using neuron-derived neurotrophic factor (NDNF) as a marker for neocortical neurogliaform cells found that while NDNF was selectively expressed in the neocortex, it was not confined to a specific subpopulation within the LHb, indicating the need for validation of molecular markers for diverse populations of neurons in different brain structures.