Parabrachial opioidergic projections to preoptic hypothalamus mediate behavioral and physiological thermal defenses.

Aaron J Norris,Michael R Bruchas,Jordan R Shaker,Aaron L Cone,Imeh B Ndiokho

doi:10.7554/elife.60779

Aaron J Norris, Michael R Bruchas + Show 3 more

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https://doi.org/10.7554/elife.60779

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Abstract

Maintaining stable body temperature through environmental thermal stressors requires detection of temperature changes, relay of information, and coordination of physiological and behavioral responses. Studies have implicated areas in the preoptic area of the hypothalamus (POA) and the parabrachial nucleus (PBN) as nodes in the thermosensory neural circuitry and indicate that the opioid system within the POA is vital in regulating body temperature. In the present study we identify neurons projecting to the POA from PBN expressing the opioid peptides dynorphin and enkephalin. Using mouse models, we determine that warm-activated PBN neuronal populations overlap with both prodynorphin (Pdyn) and proenkephalin (Penk) expressing PBN populations. Here we report that in the PBN Prodynorphin (Pdyn) and Proenkephalin (Penk) mRNA expressing neurons are partially overlapping subsets of a glutamatergic population expressing Solute carrier family 17 (Slc17a6) (VGLUT2). Using optogenetic approaches we selectively activate projections in the POA from PBN Pdyn, Penk, and VGLUT2 expressing neurons. Our findings demonstrate that Pdyn, Penk, and VGLUT2 expressing PBN neurons are critical for physiological and behavioral heat defense.

Highlights

Maintaining body temperature in the face of changing environmental conditions is a core attribute of mammals, including humans, and is critical for life
Effects of mu and kappa receptor signaling on body temperature have been described and mRNA for Pdyn and Penk has been reported to be expressed in the parabrachial nucleus (PBN) (Baker and Meert, 2002; Chen et al, 2005; Clark, 1979; Engstrom et al, 2001; Hermanson and Blomqvist, 1997; Hermanson et al, 1998)
We examined if Pdyn labeled neurons in lateral PBN (LPBN) were co-labeled by probes for Cck and found that 70% ± 0.7 of LBP Pdyn labeled neurons were co-labeled by Cck probes (Supplemental Figure 2—figure supplement 2D–F) suggesting that mRNA for Cck and pDyn is expressed in overlapping neuronal populations

Summary

Introduction

Maintaining body temperature in the face of changing environmental conditions is a core attribute of mammals, including humans, and is critical for life. Achieving a stable body temperature requires information about the temperature of the periphery and environment to be integrated to drive physiological and behavioral programs to defend the core temperature (Jessen, 1985). Physiological parameters modulated to maintain temperature include thermogenesis (utilization of brown adipose tissue [BAT], shivering), changes in circulation (vasodilation and vasoconstriction), and evaporation (Cabanac, 1975). Behavioral modifications include selection, when possible, of ambient temperature, altering posture to alter heat loss, and modulation of physical activity level. Responding to thermal challenges involves perception of temperature, encoding the valence of the temperature (e.g. too hot), and evoking appropriate physiological responses (Tan and Knight, 2018).

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