Neural Circuitry Underlying Thermal Afferent Influences During Thermoregulatory Inversion
Authors: Tupone Domenico , Cano Georgina , Conceição Ellen P. , Morrison Shaun F. 
Published: June 2021

To maintain body core temperature (TCORE) in mammals, the central nervous system thermoregulatory networks respond to skin cooling by increasing brown adipose tissue (BAT) and shivering thermogenesis, and by reducing heat loss via cutaneous vasoconstriction. However, there are several conditions (e.g., hibernation, torpor, REM sleep) in which these “standard” thermoregulatory responses to protect TCORE appear to be superseded by a “thermoregulatory inversion (TI)” in which, in contrast to normal thermoregulation, cold exposure (skin cooling) causes inhibition of thermogenesis whereas skin warming activates thermogenesis. We hypothesize that blockade or exclusion of the preoptic area (POA) thermoregulatory function is required for the initiation of thermoregulatory inversion, and that such paradoxical thermoregulation is governed by a new central thermoregulatory pathway.

We used a pre‐dorsomedial hypothalamus (pre‐DMH) brain transection or inhibition of POA (muscimol nanoinjections) to induce TI in anesthetized rats that had received an injection of the retrograde tracer, CTb, in the DMH. Warm exposure (90 min) of pre‐DMH transected rats increased BAT thermogenesis and increased Fos in DMH and in the external lateral parabrachial nucleus (elPBN) neurons projecting to DMH. In anesthetized rats after a pre‐DMH transection, inhibition of neurons in either the DMH or the elPBN blocked the warm‐evoked activation of BAT thermogenesis characteristic of TI. These results are consistent with elPBN neurons relaying warm thermal information to the DMH, resulting in activation of DMH neurons and BAT sympathetic premotor neurons in the rostral raphe pallidus (rRPa), and eliciting a warm‐evoked activation of BAT during TI.

Furthermore, we found that the cold‐evoked inhibition characteristic of TI is mediated by a population of dynorphinergic neurons in the dorsolateral PBN (dlPBN) projecting to DMH. In fact, injection of the k‐receptor antagonist, NOR‐BNI, in the DMH of pre‐DMH transected rats completely prevented the cold‐evoked BAT inhibition during TI.

Our data demonstrate that inhibition of POA is sufficient to induce TI and that a novel, short‐loop thermoregulatory pathway (skin thermoreceptors → PBN → DMH → rRPa) mediates the inverted control of BAT thermogenesis during TI. Moreover, we demonstrated that a dynorphinergic input to DMH plays a role in the cold‐evoked inhibition of BAT thermogenesis during TI.

We conclude that this line of study opens a new field of research in thermoregulation and will help to elucidate a novel mechanism for a rapid, controllable, stable and reversible induction of hypothermia, which can be beneficial for the treatment of ischemic stroke, brain trauma, and to block persistent high neurogenic fever.

Support or Funding Information

Tupone: NIH R01 NS099234, Montalcini; Morrison: NIH R01 NS091066; Cano: NIH 5P40OD010996, NIH R01 NS099234.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.