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Publication : Structural and molecular characterization of paraventricular thalamic glucokinase-expressing neuronal circuits in the mouse.

First Author  Gaspari S Year  2022
Journal  J Comp Neurol Volume  530
Issue  11 Pages  1773-1949
PubMed ID  35303367 Mgi Jnum  J:328300
Mgi Id  MGI:7335252 Doi  10.1002/cne.25312
Citation  Gaspari S, et al. (2022) Structural and molecular characterization of paraventricular thalamic glucokinase-expressing neuronal circuits in the mouse. J Comp Neurol 530(11):1773-1949
abstractText  The thalamic paraventricular nucleus (PVT) is a structure highly interconnected with several nuclei ranging from forebrain to hypothalamus and brainstem. Numerous rodent studies have examined afferent and efferent connections of the PVT and their contribution to behavior, revealing its important role in the integration of arousal cues. However, the majority of these studies used a region-oriented approach, without considering the neuronal subtype diversity of the nucleus. In the present study, we provide the anatomical and transcriptomic characterization of a subpopulation of PVT neurons molecularly defined by the expression of glucokinase (Gck). Combining a genetically modified mouse model with viral tracing approaches, we mapped both the anterograde and the retrograde projections of Gck-positive neurons of the anterior PVT (Gck(aPVT) ). Our results demonstrated that Gck(aPVT) neurons innervate several nuclei throughout the brain axis. The strongest connections are with forebrain areas associated with reward and stress and with hypothalamic structures involved in energy balance and feeding regulation. Furthermore, transcriptomic analysis of the Gck-expressing neurons revealed that they are enriched in receptors for hypothalamic-derived neuropeptides, adhesion molecules, and obesity and diabetes susceptibility transcription factors. Using retrograde labeling combined with immunohistochemistry and in situ hybridization, we identify that Gck(aPVT) neurons receive direct inputs from well-defined hypothalamic populations, including arginine-vasopressin-, melanin-concentrating hormone-, orexin-, and proopiomelanocortin-expressing neurons. This detailed anatomical and transcriptomic characterization of Gck(aPVT) neurons provides a basis for functional studies of the integration of homeostatic and hedonic aspects of energy homeostasis, and for deciphering the potential role of these neurons in obesity and diabetes development.
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