Background/Objectives: G protein-coupled trace amine-associated receptors (TAARs) belong to a family of biogenic amine-sensing receptors. TAAR1 is the best-investigated receptor of this family, and TAAR1 agonists are already being tested in clinical studies for the treatment of schizophrenia, anxiety, and depression. Meanwhile, other TAARs (TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9 in humans) are mostly known for their olfactory function, sensing innate odors. At the same time, there is growing evidence that these receptors may also be involved in brain function. TAAR8 is the least studied TAAR family member, and currently, there is no data on its function in the mammalian central nervous system. Methods: We generated triple knockout (tTAAR8-KO) mice lacking all murine Taar8 isoforms (Taar8a, Taar8b, and Taar8c) using CRISPR-Cas9 technology. In this study, we performed the first phenotyping of tTAAR8-KO mice for behavioral, electrophysiological, and neurochemical characteristics. Results: During the study, we found a number of alterations specific to tTAAR8-KO mice compared to controls. tTAAR8-KO mice demonstrated better short-term memory, more depressive-like behavior, and higher body temperature. Also, we observed changes in the dopaminergic system, brain electrophysiological activity, and adult neurogenic functions in mice lacking Taar8 isoforms. Conclusions: Based on the data obtained, it can be assumed that the physiological TAAR8 role is not limited only to the innate olfactory function, as previously proposed. TAAR8 could be involved in brain function, in particular in dopamine function regulation.

Background: Dopamine participates in the cognitive cerebellar role and in cerebellum development. The trace amine-associated receptor (TAARs, TAAR1-TAAR9) system contributes to dopamine signaling tuning. So, the aim of the present study is the analysis of the TAARs’ gene expression and functional associations in prenatal and neonatal mouse cerebellums. Methods: The transcriptomic data represented in the GEO repository was performed to identify Taars expression and co-expression patterns in embrionic and postnatal mouse cerebellum. Results: Open transcriptomic data analysis showed cerebellar expression of the Taar5 gene mRNA both in prenatal and early postnatal samples. The identified Taar5 expression was confirmed by RT-PCR in P5 mice. We identified the association between Taar5 expression and the expression of proliferation-related genes in late prenatal E13.5 samples, which was replaced by co-expression with genes involved in metabolism in P5–6 samples. These associations are suggested to mirror the previously identified Taar5 expression in Purkinje cells, which proliferate at the E13.5 and mature in the postnatal period. However, the analysis of TAAR5 co-expression with markers of different cell populations revealed the pronounced co-expression of TAAR5 in the P5–6 cerebellum with microglial markers, which is shifted to the association with astroglial markers in P10. Conclusions: The Taar5 gene was found to be active in the cerebellum samples taken around birth, and its co-expression pattern differs in the embryo stage and the early days after birth. We suggest that the Taar5 receptor may be involved in cerebellum development; however, further research is necessary to elucidate its role in this process.