Abstract
The ventral posterior hypothalamus (VPH) is an anatomically complex brain region implicated in arousal, reproduction, energy balance, and memory processing. However, neuronal cell type diversity within the VPH is poorly understood, an impediment to deconstructing the roles of distinct VPH circuits in physiology and behavior. To address this question, we employed a droplet-based single-cell RNA sequencing (scRNA-seq) approach to systematically classify molecularly distinct cell populations in the mouse VPH. Analysis of >16,000 single cells revealed 20 neuronal and 18 non-neuronal cell populations, defined by suites of discriminatory markers. We validated differentially expressed genes in selected neuronal populations through fluorescence in situ hybridization (FISH). Focusing on the mammillary bodies (MB), we discovered transcriptionally-distinct clusters that exhibit neuroanatomical parcellation within MB subdivisions and topographic projections to the thalamus. This single-cell transcriptomic atlas of VPH cell types provides a resource for interrogating the circuit-level mechanisms underlying the diverse functions of VPH circuits.
Highlights
The ventral posterior hypothalamus (VPH) is a functionally and cytoarchitecturally complex region of the hypothalamus, dominated by the mammillary bodies (MB), a discrete diencephalic structure on the basal surface of the VPH
We identified a diversity of mostly novel, and some previously identified, neuronal cell populations, many of which could be mapped to clearly defined anatomical compartments within the VPH, using both in situ hybridization (ISH) data from the Allen Brain Institute (ABA) and multiplexed fluorescence in situ hybridization (FISH)
We observed that transcriptionally-distinct MB neurons are both confined to anatomically segregated compartments and, using three genetically-targeted neuronal populations in the MB, appear to project to precise anatomical targets in the anterior thalamic nuclei (ATN)
Summary
The ventral posterior hypothalamus (VPH) is a functionally and cytoarchitecturally complex region of the hypothalamus, dominated by the mammillary bodies (MB), a discrete diencephalic structure on the basal surface of the VPH. Surrounding VPH subregions include the premammillary (PM), supramammillary (SUM), and tuberomammillary (TMN) nuclei as well as the caudal arcuate nucleus (Arc) and caudal lateral hypothalamic area (LHA). These subregions are embedded within diverse neural systems, with widespread afferents and efferents, known to regulate distinct physiological and behavioral functions (Saper and Lowell, 2014; Simerly, 2015; Card and Swanson, 2013). The functional diversity of the VPH is likely explained by cellular heterogeneity among these neuronal populations, the neural circuits they give rise to, and the complex brain-wide networks in which they are embedded. Our identification of the population structure and cellular diversity of VPH cell populations provides a resource for detailed genetic dissection of VPH circuits and interrogation of their specific roles in behavior, in both health and disease states
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