Thermoregulation in mice: The road to understanding torpor hypothermia and the shortcomings of a circuit for generating fever

In their review, “Genetic identification of preoptic neurons that regulate body in mice”, Machado and Saper [1] summarize and interpret the results of several recent studies in which the latest genetic and molecular approaches were employed to genetically specify populations of thermally responsive neurons in the preoptic area (POA) of mice and to observe the changes on core body temperature (Tc) evoked by stimulating or inhibiting their cell bodies or axon terminals. This review is a useful summary of many of the key findings related to POA thermoregulatory neurons that would need to be incorporated in functional models of the neural circuitry mediating mouse thermoregulatory responses, including not only cold- and warm-defense, but also fever and the hypothermia of cold-evoked torpor. In stark contrast to rats and humans, mice depend heavily on the cold-defense mechanisms of somatic activity thermogenesis and torpor, suggesting that there must be several aspects of the functional organiza-tion of their thermoregulatory circuitry, including that in the POA, that are unique to mice. Thus, it will be of particular interest to determine the wider applicability to other mammalian species of the new discoveries regarding central thermoregulatory circuits being made through genetic manipulation approaches in mice. However, despite several detailed studies on thermoregulatory neurons in mice, including those described in this review, many of the fundamental aspects of the neural circuits that function to explain even the most basic aspects of mouse thermoregulation, such as cold- or warm-defense, energy-conserving torpor hypothermia, and pathogen-combating fever, remain to be elucidated. The authors describe some of what is known of the considerable heterogeneity with regard to genetics, projection patterns, and receptor and neurotransmitter