PMID- 28423013 OWN - NLM STAT- MEDLINE DCOM- 20170425 LR - 20191210 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 4 DP - 2017 TI - Mapping the co-localization of the circadian proteins PER2 and BMAL1 with enkephalin and substance P throughout the rodent forebrain. PG - e0176279 LID - 10.1371/journal.pone.0176279 [doi] LID - e0176279 AB - Despite rhythmic expression of clock genes being found throughout the central nervous system, very little is known about their function outside of the suprachiasmatic nucleus. Determining the pattern of clock gene expression across neuronal subpopulations is a key step in understanding their regulation and how they may influence the functions of various brain structures. Using immunofluorescence and confocal microscopy, we quantified the co-expression of the clock proteins BMAL1 and PER2 with two neuropeptides, Substance P (SubP) and Enkephalin (Enk), expressed in distinct neuronal populations throughout the forebrain. Regions examined included the limbic forebrain (dorsal striatum, nucleus accumbens, amygdala, stria terminalis), thalamus medial habenula of the thalamus, paraventricular nucleus and arcuate nucleus of the hypothalamus and the olfactory bulb. In most regions examined, BMAL1 was homogeneously expressed in nearly all neurons (~90%), and PER2 was expressed in a slightly lower proportion of cells. There was no specific correlation to SubP- or Enk- expressing subpopulations. The olfactory bulb was unique in that PER2 and BMAL1 were expressed in a much smaller percentage of cells, and Enk was rarely found in the same cells that expressed the clock proteins (SubP was undetectable). These results indicate that clock genes are not unique to specific cell types, and further studies will be required to determine the factors that contribute to the regulation of clock gene expression throughout the brain. FAU - Frederick, Ariana AU - Frederick A AD - Centre for Studies in Behavioural Neurobiology, Concordia University, Montreal, Quebec, Canada. AD - Department of Biology, Concordia University, Montreal, Quebec, Canada. FAU - Goldsmith, Jory AU - Goldsmith J AD - Centre for Studies in Behavioural Neurobiology, Concordia University, Montreal, Quebec, Canada. AD - Department of Biology, Concordia University, Montreal, Quebec, Canada. FAU - de Zavalia, Nuria AU - de Zavalia N AD - Centre for Studies in Behavioural Neurobiology, Concordia University, Montreal, Quebec, Canada. AD - Department of Psychology, Concordia University, Montreal, Quebec, Canada. FAU - Amir, Shimon AU - Amir S AD - Centre for Studies in Behavioural Neurobiology, Concordia University, Montreal, Quebec, Canada. AD - Department of Psychology, Concordia University, Montreal, Quebec, Canada. LA - eng PT - Journal Article DEP - 20170419 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (ARNTL Transcription Factors) RN - 0 (Arntl protein, rat) RN - 0 (Enkephalins) RN - 0 (Per2 protein, rat) RN - 0 (Period Circadian Proteins) RN - 33507-63-0 (Substance P) SB - IM MH - ARNTL Transcription Factors/*genetics/metabolism MH - Amygdala/anatomy & histology/metabolism MH - Animals MH - Arcuate Nucleus of Hypothalamus/anatomy & histology/metabolism MH - Brain Mapping MH - Circadian Clocks/*genetics MH - Corpus Striatum/anatomy & histology/metabolism MH - Enkephalins/*genetics/metabolism MH - Gene Expression MH - Habenula/anatomy & histology/metabolism MH - Immunohistochemistry MH - Male MH - Nucleus Accumbens/anatomy & histology/metabolism MH - Olfactory Bulb/anatomy & histology/metabolism MH - Paraventricular Hypothalamic Nucleus/anatomy & histology/metabolism MH - Period Circadian Proteins/*genetics/metabolism MH - Rats MH - Rats, Wistar MH - Septal Nuclei/anatomy & histology/metabolism MH - Substance P/*genetics/metabolism PMC - PMC5397057 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/04/20 06:00 MHDA- 2017/04/26 06:00 PMCR- 2017/04/19 CRDT- 2017/04/20 06:00 PHST- 2016/11/29 00:00 [received] PHST- 2017/04/07 00:00 [accepted] PHST- 2017/04/20 06:00 [entrez] PHST- 2017/04/20 06:00 [pubmed] PHST- 2017/04/26 06:00 [medline] PHST- 2017/04/19 00:00 [pmc-release] AID - PONE-D-16-47265 [pii] AID - 10.1371/journal.pone.0176279 [doi] PST - epublish SO - PLoS One. 2017 Apr 19;12(4):e0176279. doi: 10.1371/journal.pone.0176279. eCollection 2017.