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Expression

It is well established that BMAL1 is heavily expressed in the Suprachiasmatic nucleus. Specifically, BMAL1 mRNA levels change throughout the day. BMAL1 transcription in the SCN displays circadian driven oscillatory activity, with highest expression at Zeitgeber time (ZT) 18 and lowest at ZT2 [1]. BMAL1 is also expressed outside of the SCN and throughout the rest of the central nervous system (CNS). BMAL1 expression has been found in the mouse amygdala and hippocampus throughout various cell types, namely pyramidal layer cells [2]. In addition, Quetiapine administration, an atypical antipsychotic drug used to treat schizophrenia, alters BMAL1 expression in both the amygdala and hippocampus. However, it is stull unknown as to what the exact role of BMAL1 is in the hippocampus and amygdala [3]. ARNTL has also been found throughout the Striatum. Specifically, its expression is most prominent in the Medium Spiny Neurons of the Striatum [4]. The exact function of BMAL1 within the striatum remains unknown but is believed to play a role in alcohol consumption. BMAL1 in the Striatum’ MSNs has a sexually dimorphic impact on alcohol consumption in mice. These sexually dimorphic roles of BMAL1 in the striatum might contribute to sex differences in alcohol consumption [5]. The cerebellum and pineal are also sites for BMAL1 expression. BMAL1 transcription is highest in the cerebellum at ZT6, and lowest at ZT18. Similarly, BMAL1 is also strongly expressed in the pineal, with similar daily rhythms [2]. BMAL 1 is also expressed in the olfactory bulbs, but with lesser daily rhythmicity [2]. BMAL1 expression is not limited to the brain areas listed above and can be found throughout the central nervous system. Interestingly, BMAL1 expression is also not restricted to the CNS and can be found in the peripheral nervous system (PNS). Its expression also exists in liver cells to regulate liver activity and synchronize it to the CNS. [6].

(1)	Abe, H., Honma, S., Namihira, M., Tanahashi, Y., Ikeda, M., & Honma, K. I. (1998). Circadian rhythm and light responsiveness of BMAL1 expression, a partner of mammalian clock gene Clock, in the suprachiasmatic nucleus of rats. Neuroscience letters, 258(2), 93-96.

(2)	Namihira, M., Honma, S., Abe, H., Tanahashi, Y., Ikeda, M., & Honma, K. I. (1999). Daily variation and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the pineal body and different areas of brain in rats. Neuroscience letters, 267(1), 69-72.

(3)	Moriya, S., Tahara, Y., Sasaki, H., Hamaguchi, Y., Kuriki, D., Ishikawa, R., ... & Shibata, S. (2014). Effect of quetiapine on Per1, Per2, and Bmal1 clock gene expression in the mouse amygdala and hippocampus. Journal of pharmacological sciences, 14071SC.

(4)	Frederick, A., Goldsmith J., de Zavalia, N., & Amir, S. (2017). Mapping the co-localization of the circadian proteins PER2 and BMAL1 with enkephalin and substance P throughout the rodent forebrain. PLoS One 12(4), Article e0176279. https://doi.org/10.1371/journal.pone.0176279

(5)	de Zavalia, N., Schottner, K., Goldsmith, J. A., Solis, P., Ferraro, S., Parent, G., & Amir, S. (2020). Sexually dimorphic influence of the circadian clock gene Bmal1 in the striatum on alcohol intake. bioRxiv.

(6)	Koronowski, K. B., Kinouchi, K., Welz, P. S., Smith, J. G., Zinna, V. M., Shi, J., ... & Sassone-Corsi, P. (2019). Defining the independence of the liver circadian clock. Cell, 177(6), 1448-1462.