Anatomical projections of the dorsomedial hypothalamus to the periaqueductal grey and their role in thermoregulation: a cautionary note.

Kathy C G De Git,Inge G Wolterink-Donselaar,Diana C Van Tuijl,Roger A H Adan,Alexander Ghanem,Mieneke C M Luijendijk,Karl-Klaus Conzelmann

doi:10.14814/phy2.13807

Kathy C G De Git, Inge G Wolterink-Donselaar + Show 5 more

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https://doi.org/10.14814/phy2.13807

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Abstract

The DMH is known to regulate brown adipose tissue (BAT) thermogenesis via projections to sympathetic premotor neurons in the raphe pallidus, but there is evidence that the periaqueductal gray (PAG) is also an important relay in the descending pathways regulating thermogenesis. The anatomical projections from the DMH to the PAG subdivisions and their function are largely elusive, and may differ per anterior–posterior level from bregma. We here aimed to investigate the anatomical projections from the DMH to the PAG along the entire anterior–posterior axis of the PAG, and to study the role of these projections in thermogenesis in Wistar rats. Anterograde channel rhodopsin viral tracing showed that the DMH projects especially to the dorsal and lateral PAG. Retrograde rabies viral tracing confirmed this, but also indicated that the PAG receives a diffuse input from the DMH and adjacent hypothalamic subregions. We aimed to study the role of the identified DMH to PAG projections in thermogenesis in conscious rats by specifically activating them using a combination of canine adenovirus‐2 (CAV2Cre) and Cre‐dependent designer receptor exclusively activated by designer drugs (DREADD) technology. Chemogenetic activation of DMH to PAG projections increased BAT temperature and core body temperature, but we cannot exclude the possibility that at least some thermogenic effects were mediated by adjacent hypothalamic subregions due to difficulties in specifically targeting the DMH and distinct subdivisions of the PAG because of diffuse virus expression. To conclude, our study shows the complexity of the anatomical and functional connection between the hypothalamus and the PAG, and some technical challenges in studying their connection.

Highlights

Humans have evolved efficient physiological mechanisms that promote the acquirement and defense of energy stores in white adipose tissue (Seale and Lazar 2009)
Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society
We aimed to compare the role of four of the identified DMH to periaqueductal gray (PAG) projections in thermoregulation by the combined use of a canine adenovirus-2 (CAV2Cre) and Cre-dependent designer receptor exclusively activated by designer drugs (DREADD) technology, a method that allows for the specific activation of neural pathways (Hnasko et al 2006; Boender et al 2014; Boekhoudt et al 2016)

Summary

Introduction

Humans have evolved efficient physiological mechanisms that promote the acquirement and defense of energy stores in white adipose tissue (Seale and Lazar 2009). Pathological accumulation of energy stores results in obesity, a condition that is difficult to counteract with dieting alone, as decreased caloric intake is followed by physiological counter regulatory mechanisms that defend acquired energy stores (Seale and Lazar 2009; Maclean et al 2011). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society

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