Development of circadian rhythmicity and light responsiveness in the rat suprachiasmatic nucleus: a study using the 2-deoxy[1-14C]glucose method.

Abstract

The suprachiasmatic nucleus (SCN) of the hypothalamus is thought to play a critical role in circadian rhythm generation and entrainment to the light/dark cycle. In adult rats, the SCN shows a circadian rhythm in metabolic activity level as indicated by 2-deoxy(1-'4Cjglucose uptake. In the present study, the development of this rhythm was investigated. No diurnal difference in uptake was evident in fetal rats 1-2 days before birth. A significant diurnal difference in SCN 2-deoxyglucose uptake was present on postnatal day 1, even in rats kept in constant darkness. By day 1, exposure to light at night increased the SCN metabolic levels. According to previous studies, on day 1 the SCN is poorly developed and contains few synapses. At this time the retinohypothalamic tract has not yet developed. We found progressive functional maturation of the SCN through day 21, when the rhythm and light responsiveness resembled those of adult rats.Three lines of evidence support the view that the suprachiasmatic nucleus (SCN) of the hypothalamus plays a critical role in generation and entrainment of circadian rhythms in mammals. First, in the rat ablation of SCN abolishes circadian rhythms in corticosterone levels (1), locomotion and drinking (2), pineal serotonin N-acetyltransferase activity (3), sleep (4), body temperature (5, 6), and events underlying estrous cyclicity (7). SCN lesions also abolish circadian rhythmicity in other mammals (8-10). This disruptive effect is not seen after ablation of areas other than the SCN or its efferents (3, 10-16). Rhythms can be entrained to light/dark cycles after ablation of all visual pathways except the retinohypothalamic tract, which projects to the SCN (17, 18), but it has not been established whether other visual pathways participate in the entrainment of circadian rhythms in the intact animal.Second, electrophysiological studies indicate that, after surgical isolation of the SCN, circadian rhythms in neuronal activity persist in the island containing the SCN but disappear in regions of the brain outside the island (19).Third, Schwartz and Gainer (20) used the 2-deoxy[1-14C]-glucose (dGlc) method to demonstrate a circadian rhythm in metabolic activity of the SCN in the intact rat brain. dGlc competes with glucose for cellular uptake; glucose is normally the sole energy source in brain. After phosphorylation, dGlc is not metabolized and accumulates as a function of neuronal metabolic energy needs. Thus, dGlc accumulation reflects an aspect of the functional state of the nervous system (21). In the adult rat there is a clear diurnal difference in dGlc uptake in the SCN but not in any other brain region examined (20,22). SCN activity is about 60% higher in the morning, in light or darkness, than it is in darkness at night. Light at night increases SCN dGlc uptake to approximately morning levels. The light responsiveness of the SCN may be an expression of its role in

Development of the mouse circadian pacemaker: Independence from environmental cycles

“…Although the precise role of the suprachiasmatic nuclei in circadian rhythmicity is as yet unknown, its recognized importance and the above findings lend support to both the notion that pacemaker properties may depend on interactions among a population of neurons, and that this area important to the generation of circadian rhythms may be subject to environmental input during its development. The later possibility is supported by the recent findings of Fuchs and Moore (1980) that the suprachiasmatic nuclei are responsive to light as early as postnatal day 1 as measured by an increase in the uptake of 2-deoxy(l-14C) glucose.…”

“…Rat fetuses have been found to show a daily rhythm in growth which is synchronized either to the mother or to the light/dark cycle to which she is exposed (Barr 1973). Furthermore, rhythms measured in rat pups shortly after birth appear to be synchronized prenatally to the mother (Deguchi 1975;Fuchs and Moore 1980). Even so, it is possible, but unlikely, that in our experiments some aspect of circadian maternal rhythmicity was not entrained to the non-24-h cycles as was wheel-running activity.…”

“…Although the age at which the pacemaker is first sensitive to light has not been determined, Fuchs and Moore (1980) have found that the suprachiasmatic nuclei of rats are responsive to light (measured as increased uptake of 2-deoxy-D-glucose) on postnatal day one. Deguchi (1975) observed an apparent difference between the periods of pineal gland rhythms in LL vs. DD treated 12-day-old rats, indicating a sensitivity of the pacemaker before that age to either light, maternal rhythmicity, or both.…”

Prenatal onset and maternal modifications of the circadian rhythm of plasma corticosterone in blind infantile rats.

“…Recently, Fuchs & Moore (1980) demonstrated a significant diurnal difference in the 2-deoxyglucose uptake by rat suprachiasmatic nuclei (s.c.n.) even on post-natal day 1, the nuclei being the first candidate for a pacemaker of circadian systems in rats, including that of plasma corticosterone.…”

Brain Circadian Oscillators and Redox Regulation in Mammals

“…Early functional measures of SCN circadian rhythmicity evaluated energy metabolism based on uptake of tracer amounts of 2-deoxy[1-14 C]glucose (21,69). This approach enables the determination of glucose consumption of individual brain structures in vivo and reports the functional activity.…”