Function And Mechanism Of Hypothalamus In Body Temperature Homeostasis

BackgroundThermohomeostasis is critical to the survival of humans and mammals.The maintenance of body temperature homeostasis depends on the body’s complex thermoregulatory system.Thermoregulation includes behavioral thermoregulation and central thermoregulation.Behavioral thermoregulation is a type of motivated,goaldirected behavior,such as by adding or removing clothing,turning on heat or air conditioning,and moving to a warm or cool environment when in a cold or hot environment.Autonomic thermoregulation refers to the autonomic heat generation and heat dissipation that occur without conscious control of the body.Autonomous thermoregulation is carried out through a feedback system consisting of temperature receptors that receive temperature signals from external and local tissues,nerve centers that control thermoregulation,and effector organs and tissues that respond to heat production and heat loss.The nerve center of thermoregulation is located in the hypothalamus,which receives and integrates temperature signals from the peripheral and central regions,sending corresponding heat production and heat dissipation signals and transmitting them to effectors.Central temperature signals are received by thermosensitive neurons and cold-sensitive neurons in hypothalamus.Besides thermosensitive neurons and cold-sensitive neurons,there are also a large number of temperature-insensitive neurons in hypothalamus.At present,there are many types of heat-sensitive and cold-sensitive neurons,but there are few researches on the types and related researches of temperature-insensitive neurons.In 2019,the research group of Yuh Nung Jan and Lily Y.Jan found that temperature-insensitive neurons highly express Camkl gene.However,no functional experiments have proved that Camk1 neurons are temperature-insensitive,and the role of such neurons in thermoregulation is still unclear.Objective1.Determine whether Camkl neuron is temperature-insensitive;2.Whether Camkl neurons are involved in thermoregulation;3.The form of Camkl neurons involved in thermoregulation.Methods1.Using adeno-associated virus(AAV)as vector to construct excitatory or inhibitory photogenetics and chemical genetics tools to specifically activate or inhibit hypothalamic thermomodulation-related nuclei or certain neurons;2.A body temperature detection system was established in mice to observe the changes in body temperature of mice when certain neurons or nuclei were activated or inhibited.3.Tissue immunofluorescence was used to observe the activation of Camkl neurons at 10℃ and 38℃;4.Clone the Camk1 promoter and construct aAV-Camk1-cre virus,verify the specificity of Camkl with primary neurons and cell lines to ensure the transcriptional activity of Camkl promoter in vivo;5.AAV virus was used as a carrier to construct calcium fluorescence probe virus(j GCaMP7s),and its sensitivity was verified by calcium flow imaging.6.Using jGCaMP7s as a tool,the activity of Camkl neurons under various conditions was recorded by optical fiber recording method.7.Frequency spectrum analysis was used to explore the form of Camkl neurons involved in body temperature homeostasis.Results1.Temperature measurement;2.The cloned Camk1 promoter virus only infects Camkl neurons;3.jGCaMP7s is sensitive to changes in calcium signal;4.Hypothalamus Camkl neurons were activated in a small amount with no significant difference during hot and cold stimulation;5.Camk1 neuronal activity was inhibited during cooling;6.Camkl neurons may be involved in temperature homeostasis in the form of frequency coding.Conclusions1.Camk1 neurons in hypothalamus are temperature-insensitive neurons;2.There are many types of neurons in hypothalamus involved in temperature homeostasis;3.CaMK1 neurons in preoptic region of hypothalamus may be involved in temperature homeostasis;4.Temperature homeostasis information may be encoded in frequency.