Exploration of thermosensory central neural pathways that drive thermoregulatory behavior

Behavioral thermoregulation is a thermoregulatory mechanism using behavioral measures, such as avoidance from cold and hot temperature, but its central circuit mechanism is largely unknown. We have previously reported that the lateral parabrachial nucleus (LPB) mediates thermosensory afferent signaling required for thermoregulatory behavior. In this study, we explored thermosensory neural pathways ascending from the LPB that mediate thermoregulatory behavior in rats.Because the LPB contains neurons sending cold- and warm-sensory signals to the thermoregulatory center, preoptic area (POA), we examined whether the LPB→POA projecting neurons are involved in behavioral thermoregulation. Retro- and anterograde adeno-associated viruses (AAV) were used to selectively express the tetanus toxin light chain (TeTxLC) in LPB→POA projecting neurons to suppress their transmission. The rats were then subjected to the two-plate thermal preference test for behavioral analysis, in which one of the plates was set at 28ºC, the thermoneutral temperature for laboratory rats, and the other was set at 39ºC (hot) or 15ºC (cold) under 25ºC room temperature. Suppressing LPB→POA projecting neurons eliminated heat avoidance, but not cold avoidance. Next, we selectively transduced LPB→POA neurons with hM4Di nrxn , an inhibitory designer receptor exclusively activated by designer drugs (DREADD). Suppression of neurotransmission at LPB→POA axon endings with microinjection of DREADD agonist 21 (C21) inhibited heat avoidance, but suppression of their axon collaterals in the dorsomedial hypothalamus did not affect thermoregulatory behavior. These results indicate that the LPB→MnPO pathway evokes heat avoidance.We explored other LPB-mediated ascending pathways for cold avoidance behavior. Our retrograde neural tracing with cholera toxin subunit (CTb) combined with immunohistochemistry for Fos, a marker for neuronal activation, revealed that a group of LPB→central amygdala (CeA) projecting neurons were activated by cold exposure. TeTxLC-mediated selective suppression of LPB→CeA transmission inhibited both cold and heat avoidance. However, optogenetic inhibition of axon endings of LPB→CeA projecting neurons through iChloC, a photosensitive chloride ion channel, eliminated cold avoidance, but not heat avoidance. Optogenetic inhibition of their axon collaterals in the ventromedial hypothalamic nucleus affected neither cold nor heat avoidance. These results indicate that the LPB→CeA pathway evokes cold avoidance. Our findings show the separate circuit structures for cold- and heat-avoidance behaviors, Moonshot R&D (JPMJMS2023 to K.N.) of the Japan Science and Technology Agency; Grants-in-Aid for Scientific Research (JP22K06470 to N.K.; JP20H03418 and JP15H05932 to K.N.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Agency for Medical Research and Development (JP21wm0525002 to N.K.); Takeda Science Foundation (to T.Y) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.