Extended Data Fig. 17: Additional evidence for DPd projections to hypothalamic neuroendocrine zone.
a, Anterograde tracing confirms specificity of DPd’s projections to hypothalamic neuroendocrine zone and periventricular structures including MPO (GnRH neurons), PVa (somatostatin neurons), and SO (oxytocin, vasopressin neurons). DPd innervates periventricular and medial hypothalamic structures involved in homeostatic regulation, like the anteroventral periventricular nucleus (AVPV) and MPN, two sexually dimorphic areas essential for sex hormone control and reproductive behaviours. Scale bars = 500 µm. b, 2D hierarchical clustering illustrates the comparative projections from MPF areas and TTd to the hypothalamic periventricular zone (PVZ). The DPd generates unique projections throughout the PVZ. The DPs and other MPF areas display minimal to no projections to the PVZ. c, Bar graph shows DPd, unlike other MPF areas, generates dense projections to neuroendocrine PVHmpd and PVHpv regions, compared to the graph showing DPs projections to autonomic PVHlp and PVHf (Extended Data Fig. 15b). d, Flatmap showing the spatial distribution of hypothalamic neuroendocrine cell populations across rostral-caudal levels. Gonadotropin-releasing hormone (GnRH) neurons localize in preoptic area; somatostatin (SS) neurons in intermediate periventricular nucleus (PVi) and PVHpv (periventricular part of the PVH); thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH) neurons in PVH medial parvicellular division (PVHmpd); dopamine and growth hormone–releasing hormone (GRH) neurons are in arcuate nucleus (ARH), where dopamine regulates prolactin secretion. Two magnocellular neuron types, oxytocin (OXY) and vasopressin, distribute across the magnocellular division of PVH (PVHm), supraoptic nucleus (SO), and accessory supraoptic nucleus (ASO). The longitudinal organization of the hypothalamus contains three major zones: periventricular (PVZ), medial (MEZ), and lateral (LZ). e-g, Pareto charts (left) compare quantified labelling in arcuate (ARH, e), medial preoptic nucleus (MPN, f), and dorsomedial hypothalamic nuclei (DMH, g) following anterograde MPF tracer injections. Right y axis denotes cumulative percentage. Strongest projectionss to these hypothalamic regions are from DPd. Right panels validate these strong DP→ARH/MPN/DMH connections with retrograde tracer injections (CTB, FG), supporting unique DPd projections to the periventricular hypothalamic region.
