Abstract
In mammals, a light-entrainable clock located in the suprachiasmatic nucleus (SCN) regulates circadian rhythms by synchronizing oscillators throughout the brain and body. Notably, the nature of the relation between the SCN clock and subordinate oscillators in the rest of the brain is not well defined. We performed a high temporal resolution analysis of the expression of the circadian clock protein PERIOD2 (PER2) in the rat forebrain to characterize the distribution, amplitude and phase of PER2 rhythms across different regions. Eighty-four LEW/Crl male rats were entrained to a 12-h: 12-h light/dark cycle, and subsequently perfused every 30 min across the 24-h day for a total of 48 time-points. PER2 expression was assessed with immunohistochemistry and analyzed using automated cell counts. We report the presence of PER2 expression in 20 forebrain areas important for a wide range of motivated and appetitive behaviors including the SCN, bed nucleus, and several regions of the amygdala, hippocampus, striatum, and cortex. Eighteen areas displayed significant PER2 rhythms, which peaked at different times of day. Our data demonstrate a previously uncharacterized regional distribution of rhythms of a clock protein expression in the brain that provides a sound basis for future studies of circadian clock function in animal models of disease.
Highlights
Circadian rhythms establish the timing of biological systems in order to optimize physiology, behavior and health [1,2]
Consistent with this suggestion, we have identified robust daily rhythms in expression of PER2 in five functionally and anatomically interconnected regions of the rat limbic forebrain, the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), the lateral part of the central amygdala (CEAl), the basolateral amygdala (BLA), the dentate gyrus (DG) of the hippocampus, and the dorsal striatum [12,13,14,15]
The rhythms found in the BLA, DG, and striatum peaked at the opposite time of day, in the morning, revealing distinct phase relationships between PER2 oscillations in different forebrain nuclei and the PER2 rhythm in the suprachiasmatic nucleus (SCN)
Summary
Circadian rhythms establish the timing of biological systems in order to optimize physiology, behavior and health [1,2] In mammals, these rhythms are generated by a network of cellular clocks scattered throughout the brain and periphery, and governed by a master pacemaker located in the suprachiasmatic nucleus of the hypothalamus, SCN [3]. Daily rhythms in the expression of PER2 and other clock genes and proteins have been seen in many other neural structures that are not considered intrinsically rhythmic, suggesting that many brain nuclei harbor functional circadian clocks [10,11] Consistent with this suggestion, we have identified robust daily rhythms in expression of PER2 in five functionally and anatomically interconnected regions of the rat limbic forebrain, the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), the lateral part of the central amygdala (CEAl), the basolateral amygdala (BLA), the dentate gyrus (DG) of the hippocampus, and the dorsal striatum [12,13,14,15]. The rhythms found in the BLA, DG, and striatum peaked at the opposite time of day, in the morning, revealing distinct phase relationships between PER2 oscillations in different forebrain nuclei and the PER2 rhythm in the SCN
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