Hypothalamic warm-sensitive neurons require TRPC4 channel for detecting internal warmth and regulating body...

Area of Science:

• Neuroscience
• Physiology
• Molecular Biology

Background:

• Mammalian thermal homeostasis relies on precise internal temperature monitoring.
• Warm-sensitive neurons (WSNs) in the preoptic area (POA) were historically considered key temperature sensors.
• The precise cellular and molecular mechanisms of WSN temperature sensing remained largely unknown.

Purpose of the Study:

• To investigate the molecular mechanisms underlying temperature sensing in WSNs.
• To identify novel cellular components involved in regulating core body temperature (T_core).
• To explore the role of the TRPC4 channel in mammalian thermoregulation.

Main Methods:

• Pilot genetic screen to identify genes involved in thermoregulation.
• Silencing and loss-of-function studies of the TRPC4 channel in mice.
• Utilizing light-mediated heating of the POA to induce hypothermia.
• Administration of TRPC4 antagonists and agonists.

Main Results:

• Silencing TRPC4 attenuated light-induced hypothermia in mice.
• Loss of TRPC4 function impaired warm sensing in GABAergic WSNs.
• TRPC4 deficiency affected basal temperature, warm defense, and fever responses.
• TRPC4 antagonists and agonists bidirectionally modulated T_core.

Conclusions:

• TRPC4 channels are essential for sensing internal warmth in the brain.
• TRPC4-expressing GABAergic WSNs act as a novel cellular sensor to prevent hyperthermia.
• TRPC4 presents a potential therapeutic target for managing body temperature.