TAAR8 in the Brain: Implications for Dopaminergic Function, Neurogenesis, and Behavior

Area of Science:

• Neuroscience
• Receptor Biology
• Genetics

Background:

• Trace amine-associated receptors (TAARs) are biogenic amine-sensing receptors.
• TAAR1 agonists are in clinical trials for psychiatric disorders.
• Other TAARs, including TAAR8, are primarily linked to olfactory function, but potential brain roles are emerging.

Purpose of the Study:

• To investigate the function of TAAR8 in the mammalian central nervous system.
• To perform the first phenotyping of mice lacking all murine Taar8 isoforms (tTAAR8-KO).

Main Methods:

• Generation of triple knockout (tTAAR8-KO) mice using CRISPR-Cas9.
• Comprehensive phenotyping including behavioral, electrophysiological, and neurochemical analyses.

Main Results:

• tTAAR8-KO mice exhibited enhanced short-term memory, depressive-like behavior, and elevated body temperature.
• Significant alterations were observed in the dopaminergic system and brain electrophysiology.
• Changes in adult neurogenic functions were noted in mice lacking Taar8 isoforms.

Conclusions:

• TAAR8's physiological role extends beyond innate olfactory function.
• TAAR8 is implicated in central nervous system functions, particularly in regulating dopamine.
• These findings open new avenues for understanding TAAR8's involvement in neurological processes.