Preoptic BRS3 neurons increase body temperature and heart rate via multiple pathways

Abstract

Highlights d POA BRS3 neuron activation increases body temperature and heart rate d POA BRS3 neurons increase body temperature via multiple effector paths (PVH, DMH, PAG) d POA BRS3 neurons contribute to defense from a cold environment d POA BRS3 neurons fine-tune feedback control of body temperature, reducing variability

Prostaglandin EP3 receptor-expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling

“…Therefore, these subgroups likely mediate heat defense and some of them may drive torpor when mice are hungry in cold environments, but they seem unlikely to function for cold defense or fever. Another group of POA neurons expressing bombesin-like receptor 3 (BRS3) is activated by cooling of mice and drive cold-defensive responses, but do not mediate LPS-induced fever (Piñol et al, 2021). Chemogenetic inhibition of BRS3-expressing POA neurons elicits only a modest decrease (0.5°C) in T core (Piñol et al, 2021).…”

“…Another group of POA neurons expressing bombesin-like receptor 3 (BRS3) is activated by cooling of mice and drive cold-defensive responses, but do not mediate LPS-induced fever (Piñol et al, 2021). Chemogenetic inhibition of BRS3-expressing POA neurons elicits only a modest decrease (0.5°C) in T core (Piñol et al, 2021). In contrast, the present study showed that POA EP3R neurons, which are activated by heat exposure and inhibited by PGE 2 , bidirectionally control T core .…”

“…This mechanism is consistent with the view that the POA EP3R →DMH GABAergic signaling, whose tone is altered by cutaneous and central thermosensory signals, makes a major contribution to setting the control range of T core . The glutamatergic inputs from the POA to sympathoexcitatory DMH neurons may also be regulated by thermosensory signals (activated by cold) (Tanaka et al, 2011; da Conceição et al, 2020; Piñol et al, 2021). However, sympathoexcitatory DMH neurons also likely receive temperature-independent, intense excitatory signals from other brain sites perhaps located caudal to the POA, because a complete disruption of fibers descending from the POA elicits robust BAT thermogenesis and cutaneous vasoconstrictor activity leading to hyperthermia (Chen et al, 1998; Rathner et al, 2008).…”

“…Another potential reason may be that skin warming with a water jacket to maintain Tcore of the anesthetized rats inhibited the POA→DMH glutamatergic excitatory transmission that is required for the excitation of sympathoexcitatory DMH 12 neurons after withdrawal of the GABAergic inhibition from POA EP3R neurons (Tanaka et al, 2011;da Conceição et al, 2020;Piñol et al, 2021). The balance between GABAergic and glutamatergic inputs from the POA to the DMH is considered important for the activity control of the DMH→rMR neurons that drive thermogenic sympathetic outflow (Morrison and Nakamura, 2019;Nakamura et al, 2022) 6C-E).…”

Cre Recombinase Driver Mice Reveal Lineage-Dependent and -Independent Expression of Brs3 in the Mouse Brain

“…Brs3 neurons in the paraventricular hypothalamus (PVH) regulate food intake, but not body temperature or BAT thermogenesis. In contrast, Brs3 neurons in the preoptic area (POA) of the hypothalamus and dorsomedial hypothalamus (DMH) regulate body temperature, energy expenditure, heart rate, and blood pressure, but not appetite ( Piñol et al, 2018 , 2021 ). POA Brs3 neurons have also been implicated in parental behaviors ( Moffitt et al, 2018 ; Yoshihara et al, 2021 ).…”