TOPOGRAPHY OF GALANIN AND NEUROPEPTIDE-Y LOCUS COERULEUS NEURONS AND THEIR HIPPOCAMPAL OUTPUTS

While the locus coeruleus (LC) was originally regarded as the noradrenergic hub of the brain, recent studies have shown it to be highly diverse in nature. The same LC neuron can target functionally related structures and can release dopamine and neuropeptides together with noradrenaline in a frequency-dependent manner (doi:10.1002/(SICI)1096-9861(19970818)385:1<135::AID-CNE8>3.0.CO;2-3, doi:10.1002/hipo.23419). Additionally, the LC projects heterogeneously to the hippocampus, exhibiting different intensities of afferent distributions depending on the hippocampal subfield or dorsoventral axis components (doi:10.1016/0006-8993(85)90342-7).
Here, we addressed how LC projections to dorsal and ventral hippocampus, and particularly the dentate gyrus, differ, and if these populations are distinct regarding their neuropeptide expression. To implement this, Long Evans rats received bilateral injections of retrograde tracers in the dorsal and ventral dentate gyrus. This approach was combined with immunofluorescence staining for galanin and neuropeptide-Y (NPY) report that there is broad, differentiated innervation of the hippocampus by LC, similar to previous findings. We then used the image segmentations of the manually counted cells to classify the entire LC cell population by combining Cellpose for automatic cell-segmentation of all LC cells and XGBoost, a commonly used tree boosting algorithm for classification, to scrutinize the LC and its galanin- and NPY-positive populations. We identified both overlapping and segregated expression of the peptides. Our results show a similar distribution of neuropeptides for the two mostly separate cell populations in LC innervating the hippocampal poles.
Acknowledgements: Funded by German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) grants to D.M.V (SPP 2411 - project number: 520284247, RTG 2862, project number: 492434978).