Comprehensive thermal preference phenotyping in mice using a novel automated circular gradient assay

Area of Science:

• Neuroscience
• Behavioral Science
• Physiology

Background:

• Existing mouse cold sensitivity assays yield conflicting results and lack sensitivity.
• Current methods struggle to detect subtle changes in cold nociception, especially those related to ion channel function.
• Limitations include restricted thermal spectrum, experimenter bias, and insufficient sensitivity for detecting minor behavioral alterations.

Purpose of the Study:

• To develop a novel, automated behavioral assay for precise quantification of cold sensitivity, hypersensitivity, and hyperalgesia in mice.
• To overcome the limitations of current assays, including experimenter bias and restricted thermal range.
• To enable accurate phenotyping of thermal sensitivity in genetically modified mouse models.

Main Methods:

• Designed a novel automated thermal gradient assay as a circular running track.
• The device offers a high degree of thermal choice and eliminates experimenter bias.
• Utilized custom-designed automated offline analysis with a blob detection algorithm, validated for accuracy and artifact removal.

Main Results:

• The assay accurately distinguishes exploratory from thermal selection behavior.
• It provides precise measurements of thermal preference and distribution skew.
• Demonstrated increased accuracy in phenotyping transgenic mice, revealing novel details on TRPM8, TRPA1, and double-deficient models.

Conclusions:

• The novel automated thermal gradient assay offers a significant advancement in quantifying mouse thermal sensitivity.
• This assay overcomes limitations of previous methods, providing more accurate and detailed phenotyping.
• It is particularly valuable for studying the roles of ion channels in cold sensing and for analyzing genetically modified mouse models.