Transduction Mechanisms for Cold Temperature in Mouse Trigeminal and Vagal Ganglion Neurons Innervating Different...

Area of Science:

• Neuroscience
• Molecular Biology
• Sensory Physiology

Background:

• Cold sensing is crucial for survival and involves specialized sensory neurons.
• The molecular mechanisms underlying cold detection in visceral sensory neurons are not fully understood.
• Trigeminal ganglia (TG) are associated with somatic sensation, while vagal ganglia (VG) innervate visceral organs.

Purpose of the Study:

• To compare the molecular mechanisms of cold sensing in mouse trigeminal (TG) and vagal ganglia (VG).
• To elucidate the roles of Transient Receptor Potential Melastatin 8 (TRPM8) and Transient Receptor Potential Ankyrin 1 (TRPA1) channels in visceral cold transduction.

Main Methods:

• Side-by-side characterization of cold-sensitive (CS) neurons in adult mouse TG and VG.
• Utilized a combination of physiological, pharmacological, molecular, and genetic approaches.
• Employed Trpa1 knockout (KO) and Trpm8 reporter mice for in vivo analysis.

Main Results:

• VG exhibited a higher abundance of CS neurons, predominantly co-expressing TRPA1. Trpa1 KO mice showed blunted cold responses.
• TRPM8 played a minor role in VG cold sensitivity; its expression was limited to specific VG regions.
• TG CS neurons mainly co-expressed TRPM8, with TRPM8 deletion/blockade reducing cold sensitivity. TRPA1 contributed to high-threshold cold sensing in TG.
• A subset of CS neurons in both ganglia utilized TRPA1/TRPM8-independent mechanisms, modulated by potassium channel activity.

Conclusions:

• TRPA1 channels are critical for visceral cold transduction in VG, contrasting with the predominant TRPM8 role in TG cold sensing.
• Cold sensitivity mechanisms are differentially adapted to the specific physiological requirements of various organs.
• This study establishes distinct molecular underpinnings for cold sensation in somatic versus visceral pathways.