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. 2014 Mar 21;9(3):e92959.
doi: 10.1371/journal.pone.0092959. eCollection 2014.

Light stimulates the mouse adrenal through a retinohypothalamic pathway independent of an effect on the clock in the suprachiasmatic nucleus

Affiliations

Light stimulates the mouse adrenal through a retinohypothalamic pathway independent of an effect on the clock in the suprachiasmatic nucleus

Silke Kiessling et al. PLoS One. .

Abstract

The brain's master circadian pacemaker resides within the hypothalamic suprachiasmatic nucleus (SCN). SCN clock neurons are entrained to the day/night cycle via the retinohypothalamic tract and the SCN provides temporal information to the central nervous system and to peripheral organs that function as secondary oscillators. The SCN clock-cell network is thought to be the hypothalamic link between the retina and descending autonomic circuits to peripheral organs such as the adrenal gland, thereby entraining those organs to the day/night cycle. However, there are at least three different routes or mechanisms by which retinal signals transmitted to the hypothalamus may be conveyed to peripheral organs: 1) via retinal input to SCN clock neurons; 2) via retinal input to non-clock neurons in the SCN; or 3) via retinal input to hypothalamic regions neighboring the SCN. It is very well documented that light-induced responses of the SCN clock (i.e., clock gene expression, neural activity, and behavioral phase shifts) occur primarily during the subjective night. Thus to determine the role of the SCN clock in transmitting photic signals to descending autonomic circuits, we compared the phase dependency of light-evoked responses in the SCN and a peripheral oscillator, the adrenal gland. We observed light-evoked clock gene expression in the mouse adrenal throughout the subjective day and subjective night. Light also induced adrenal corticosterone secretion during both the subjective day and subjective night. The irradiance threshold for light-evoked adrenal responses was greater during the subjective day compared to the subjective night. These results suggest that retinohypothalamic signals may be relayed to the adrenal clock during the subjective day by a retinal pathway or cellular mechanism that is independent of an effect of light on the SCN neural clock network and thus may be important for the temporal integration of physiology and metabolism.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The effect of light on SCN and adrenal gene expression and plasma hormone levels.
A: Relative density of Per1, Per2 and c-fos expression in the SCN following a light pulse (LP; 30 min at 350 lux) beginning at the indicated circadian time (CT) points compared to dark control (DC) mice. B: Relative expression of Per1 and Per2 in the adrenal following a LP compared to DC animals at several CT points throughout the subjective day and subjective night. C: Plasma levels of corticosterone (left) and ACTH (right) following a LP at the indicated CT points. The differences between DC and LP values at each CT point are indicated by asterisks; *p<0.05, **p<0.01, ***p<0.001); n = 4–12 animals/group/CT point.
Figure 2
Figure 2. Irradiance dependent effect of light on plasma corticosterone and adrenal Per1 and Per2 expression.
The effects of a 30(A, top row), adrenal Per1 mRNA expression (B, middle row), and adrenal Per2 mRNA expression (C, bottom row). Samples were collected 60 min after the beginning of the light pulse during the subjective day at circadian time (CT) 2, CT4, and CT6. The differences between dark controls (0 lux) and light-pulsed animals are indicated by asterisks (*p<0.05, **p<0.01, ***p<0.001), to 35 lux light-pulsed animals by plus signs (+p<0.05, ++p<0.01) and to 350 lux light-pulsed animals by dots (··p<0.01); One-Way ANOVA, n = 4–9 animals/group.
Figure 3
Figure 3. Effect of light on plasma ACTH and adrenal StAR and MC2R during the subjective day.
A: The effect of a 30 min light pulse during the subjective day on plasma ACTH. B: Relative mRNA expression of StAR in the adrenal following a 30 min light pulse. C: Relative mRNA expression of MC2R in the adrenal following a 30 min light pulse. Samples were collected 60 min after the beginning of the light pulse of either 35, 350 or 3500 lux during the subjective day at circadian time (CT) 2, CT4, and CT6. No significant differences were observed in plasma ACTH, adrenal StAR mRNA, or adrenal MC2R mRNA expression between light-pulsed and dark control (0 lux) animals at any of the CT points examined; One-Way ANOVA, n = 4–9 animals/group.
Figure 4
Figure 4. Circadian profiles of adrenal TH and PNMT and following light stimulation during the subjective day.
A: Relative expression of adrenal tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) at several circadian time (CT) points. B: Relative expression of adrenal TH and PNMT following a 30 min light-pulse. Samples were collected 60 min after the beginning of the light pulse of either 35, 350 or 3500 lux during the subjective day at circadian time (CT) 2, CT4, and CT6. Significant differences compared to dark controls (0 lux) are indicated by asterisks (*p<0.05, **p<0.01, ***p<0.001), to 35 lux light pulses by plus signs (++p<0.01, +++p<0.001) and to 350 lux light pulses by dots (·p<0.05, ···p<0.001); One-Way ANOVA; n = 4–11 animals/group.

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