SCN-lesioned Animals Research Articles

Loss of Circadian Timing Disrupts Theta Episodes during Object Exploration.

This study examined whether theta oscillations were compromised by the type of circadian disruption that impairs hippocampal-dependent memory processes. In prior studies on Siberian hamsters, we developed a one-time light treatment that eliminated circadian timing in the central pacemaker, the suprachiasmatic nucleus (SCN). These arrhythmic animals had impaired hippocampal-dependent memory whereas animals made arrhythmic with SCN lesions did not. The current study examined whether theta oscillations are compromised by the same light treatment that produced memory impairments in these animals. We found that both methods of inducing circadian-arrhythmia shortened theta episodes in the EEG by nearly 50%. SCN-lesioned animals, however, exhibited a 3-fold increase in the number of theta episodes and more than doubled the total time that theta dominated the EEG compared to SCN-intact circadian-arrhythmic animals. Video tracking showed that changes in theta were paralleled by similar changes in exploration behavior. These results suggest that the circadian-arrhythmic SCN interferes with hippocampal memory encoding by fragmenting theta oscillations. SCN-lesioned animals can, however, compensate for the shortened theta episodes by increasing their frequency. Implications for rhythm coherence and theta sequence models of memory formation are discussed.

The Suprachiasmatic Nucleus Modulates the Sensitivity of Arcuate Nucleus to Hypoglycemia in the Male Rat.

The suprachiasmatic nucleus (SCN) and arcuate nucleus (ARC) have reciprocal connections; catabolic metabolic information activates the ARC and inhibits SCN neuronal activity. Little is known about the influence of the SCN on the ARC. Here, we investigated whether the SCN modulated the sensitivity of the ARC to catabolic metabolic conditions. ARC neuronal activity, as determined by c-Fos immunoreactivity, was increased after a hypoglycemic stimulus by 2-deoxyglucose (2DG). The highest ARC neuronal activity after 2DG was found at the end of the light period (zeitgeber 11, ZT11) with a lower activity in the beginning of the light period (zeitgeber 2, ZT2), suggesting the involvement of the SCN. The higher activation of ARC neurons after 2DG at ZT11 was associated with higher 2DG induced blood glucose levels as compared with ZT2. Unilateral SCN-lesioned animals, gave a mainly ipsilateral activation of ARC neurons at the lesioned side, suggesting an inhibitory role of the SCN on ARC neurons. The 2DG-induced counterregulatory glucose response correlated with increased ARC neuronal activity and was significantly higher in unilateral SCN-lesioned animals. Finally, the ARC as site where 2DG may, at least partly, induce a counterregulatory response was confirmed by local microdialysis of 2DG. 2DG administration in the ARC produced a higher increase in circulating glucose compared with 2DG administration in surrounding areas such as the ventromedial nucleus of the hypothalamus (VMH). We conclude that the SCN uses neuronal pathways to the ARC to gate sensory metabolic information to the brain, regulating ARC glucose sensitivity and counterregulatory responses to hypoglycemic conditions.

Simulated shift work in rats perturbs multiscale regulation of locomotor activity.

Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation.

The suprachiasmatic nucleus is part of a neural feedback circuit adapting blood pressure response

The suprachiasmatic nucleus (SCN) is typically considered our autonomous clock synchronizing behavior with physiological parameters such as blood pressure (BP), just transmitting time independent of physiology. Yet several studies show that the SCN is involved in the etiology of hypertension. Here, we demonstrate that the SCN is incorporated in a neuronal feedback circuit arising from the nucleus tractus solitarius (NTS), modulating cardiovascular reactivity. Tracer injections into the SCN of male Wistar rats revealed retrogradely filled neurons in the caudal NTS, where BP information is integrated. These NTS projections to the SCN were shown to be glutamatergic and to terminate in the ventrolateral part of the SCN where light information also enters. BP elevations not only induced increased neuronal activity as measured by c-Fos in the NTS but also in the SCN. Lesioning the caudal NTS prevented this activation. The increase of SCN neuronal activity by hypertensive stimuli suggested involvement of the SCN in counteracting BP elevations. Examining this possibility we observed that elevation of BP, induced by α1-agonist infusion, was more than twice the magnitude in SCN-lesioned animals as compared to in controls, indicating indeed an active involvement of the SCN in short-term BP regulation. We propose that the SCN receives BP information directly from the NTS enabling it to react to hemodynamic perturbations, suggesting the SCN to be part of a homeostatic circuit adapting BP response. We discuss how these findings could explain why lifestyle conditions violating signals of the biological clock may, in the long-term, result in cardiovascular disease.

The methamphetamine-sensitive circadian oscillator is dysfunctional in a transgenic mouse model of Huntington's disease

A progressive disintegration of the rest-activity rhythm has been observed in the R6/2 mouse model of Huntington's disease (HD). Rest-activity rhythm is controlled by a circadian clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus, although SCN-independent oscillators such as the methamphetamine (MAP)-sensitive circadian oscillator (MASCO) can also control rhythmicity, even in SCN-lesioned animals. We aimed to test whether or not the administration of MAP could restore a normal rest-activity rhythm in R6/2 mice, via the activation of the MASCO. We administered chronic low doses of MAP to wild-type (WT) and presymptomatic (7–8weeks) R6/2 mice, in constant darkness. As expected, ~40% of the WT mice expressed a rest-activity rhythm controlled by the MASCO, with a period of around 32h. By contrast, the MASCO was missing from almost 95% of the R6/2 mice, even at early stages of disease. Interestingly, although the MASCO was deficient, initially MAP was able to stabilize the day/night activity ratio in R6/2 mice and delay the onset of disintegration of the rest-activity rhythm driven by the SCN. Furthermore, in presymptomatic R6/2 mice treated with L-DOPA, a MASCO-like component began to emerge, although this never became established. Our data show a major dysfunction of the MASCO in presymptomatic R6/2 mice that is likely to be due to an early abnormality of the catecholaminergic systems. We suggest that the dysfunction of the MASCO in humans could be partially responsible for circadian disturbances observed in HD patients, as well as patients with other neurological diseases in which both catecholaminergic and circadian abnormalities are present, such as Parkinson's disease and schizophrenia.

Circadian variations of prostaglandin E2 and F2 α release in the golden hamster retina

Circadian variations of prostaglandin E2 and F2alpha release were examined in the golden hamster retina. Both parameters showed significant diurnal variations with maximal values at midnight. When hamsters were placed under constant darkness for 48 h, the differences in prostaglandin release between subjective mid-day and subjective midnight persisted. Western blot analysis showed that cyclooxygenase (COX)-1 levels were significantly higher at midnight than at mid-day, and at subjective midnight than at subjective mid-day, whereas no changes in COX-2 levels were observed among these time points. Immunohistochemical studies indicated the presence of COX-1 and COX-2 in the inner (but not outer) retina. Circadian variations of retinal prostaglandin release were also assessed in suprachiasmatic nuclei (SCN)-lesioned animals. Significant differences in retinal prostaglandin release between subjective mid-day and subjective midnight were observed in SCN-lesioned animals. These results indicate that hamster retinal prostaglandin release is regulated by a retinal circadian clock independent from the SCN. Thus, the present results suggest that the prostaglandin/COX-1 system could be a retinal clock output or part of the retinal clock mechanism.

Reduction of scale invariance of activity fluctuations with aging and Alzheimer's disease: Involvement of the circadian pacemaker

Human motor control systems orchestrate complex scale-invariant patterns of activity over a wide range of time scales (minutes to hours). The neural mechanisms underlying scale-invariance are unknown in humans. In rats, the master circadian pacemaker [suprachiasmatic nucleus (SCN)] is crucially involved in scale-invariant activity fluctuations over multiple time scales from minutes to 24 h. Aging and Alzheimer's disease (AD) are associated with progressive dysfunction of the SCN. Thus, if the SCN is responsible for the scale-invariant activity fluctuations in humans, we predict disturbances of scale-invariant activity fluctuations in elderly humans and even more pronounced disturbances in elderly humans with AD. To test these hypotheses, we studied spontaneous daytime activity patterns in 13 young adults (mean +/- SD: 25.5 +/- 6.1 y); 13 elderly people with early-stage AD (68.5 +/- 6.1 y) matched with 13 elderly controls (68.6 +/- 6.1 y); and 14 very old people with late-stage AD (83.9 +/- 6.7 y) matched with 12 very old controls (80.8 +/- 8.6 y). In young adults, activity exhibited robust scale-invariant correlations across all tested time scales (minutes to 8 h). The scale-invariant correlations at 1.5-8 h declined with age (P = 0.01) and were significantly reduced in the elderly (P = 0.04) and very old controls (P = 0.02). Remarkably, an age-independent AD effect further reduced the scale-invariant correlations at 1.5-8 h (P = 0.04), leading to the greatest reduction of the scale-invariant correlations in very old people with late-stage AD-resembling closely the loss of correlations at large time scales in SCN-lesioned animals. Thus, aging and AD significantly attenuate the scale invariance of activity fluctuations over multiple time scales. This attenuation may reflect functional changes of the SCN.

Effects of suprachiasmatic nucleus lesions on habituation of the head-shake response

Habituation is a form of non-associative learning that is characterized by a decrease in responsiveness to a repeatedly presented stimulus. A useful model of mammalian habituation is the head-shake response (HSR), a rapid twisting of the head about the anterior-to-posterior axis elicited by a stream of air to the ear. The behavioral properties of HSR habituation include sensitivity to rate of stimulus presentation and a very predictable pattern of spontaneous recovery, suggesting that a neural timing mechanism is involved. One possible candidate is the suprachiasmatic nucleus (SCN) of the hypothalamus which utilizes "clock genes" to generate daily rhythms in behavior. To test this hypothesis, the effects of SCN lesions on habituation and recovery of the HSR were assessed across four inter-session intervals (ISI: 5 min, 2, 24, and 48 h) in rats. SCN-lesioned animals showed a significant decrease in responsiveness within sessions and impaired spontaneous recovery with the 24h ISI condition. The present findings suggest that the SCN may mediate temporal patterning of spontaneous recovery from habituation and is necessary in order to appropriately reset the animal to its pre-habituation level of responsiveness.

Circadian Rhythms: Per2bations in the Liver Clock

A master circadian clock resides in the brain and is required to synchronize the clocks in peripheral tissues such as the liver. Until now, it has been unclear how the central clock synchronizes the peripheral ones. New work points to one of the core clock genes, mPer2, as an essential link in this chain.

Environmental light and suprachiasmatic nucleus interact in the regulation of body temperature

The mammalian biological clock, located in the suprachiasmatic nucleus (SCN), is crucial for circadian rhythms in physiology and behavior. However, equivocal findings have been reported on its role in the circadian regulation of body temperature. The goal of the present studies was to investigate the interaction between the SCN and environmental light in the regulation of body temperature. All recordings were performed by telemetry in free moving male Wistar rats. Firstly, we demonstrated an endogenous circadian rhythm in body temperature independent of locomotor activity. This rhythm was abolished by stereotactic lesioning of the SCN. Secondly, we demonstrated a circadian phase-dependent suppressive effect of light (‘negative masking’) on body temperature. Light suppressed body temperature more at the end of the subjective night (circadian time [CT] 22) than in the middle (CT 6) and at the end (CT 10) of the subjective day. This circadian-phase dependent suppression was not demonstrated in SCN-lesioned animals. Surprisingly, after half a year of recovery from lesioning of the SCN, light regained its suppressing action on body temperature, resulting in a daily body temperature rhythm only under light–dark conditions. In contrast to body temperature, light could not substantially mimic a daytime inhibitory SCN-output in the regulation of heart rate and locomotor activity. The present results suggest that, after lesioning of the SCN as main relay station for the immediate body temperature-inhibition by light, secondary relay nuclei can fully take over this function of the SCN. These findings provide a possible explanation for the controversy in literature over the question whether the SCN is required for the diurnal rhythm in body temperature. Furthermore, they show that light may have an acute effect on behavior and physiology of the organism via the SCN, which extends beyond the generally acknowledged effect on melatonin secretion.

Daily Variations in Type II Iodothyronine Deiodinase Activity in the Rat Brain as Controlled by the Biological Clock

Type II deiodinase (D2) plays a key role in regulating thyroid hormone-dependent processes in, among others, the central nervous system (CNS) by accelerating the intracellular conversion of T4 into active T3. Just like the well-known daily rhythm of the hormones of the hypothalamo-pituitary-thyroid axis, D2 activity also appears to show daily variations. However, the mechanisms involved in generating these daily variations, especially in the CNS, are not known. Therefore, we decided to investigate the role the master biological clock, located in the hypothalamus, plays with respect to D2 activity in the rat CNS as well as the role of one of its main hormonal outputs, i.e. plasma corticosterone. D2 activity showed a significant daily rhythm in the pineal and pituitary gland as well as hypothalamic and cortical brain tissue, albeit with a different timing of its acrophase in the different tissues. Ablation of the biological clock abolished the daily variations of D2 activity in all four tissues studied. The main effect of the knockout of the suprachiasmatic nuclei (SCN) was a reduction of nocturnal peak levels in D2 activity. Moreover, contrary to previous observations in SCN-intact animals, in SCN-lesioned animals, the decreased levels of D2 activity are accompanied by decreased plasma levels of the thyroid hormones, suggesting that the SCN separately stimulates D2 activity as well as the hypothalamo-pituitary-thyroid axis.

Convergence of circadian and sleep regulatory mechanisms on hypocretin-1

Hypocretin is a potential regulator of sleep and wakefulness and its levels fluctuate with the day–night cycle with high levels during the animal's activity period. Whether the daily fluctuations are driven endogenously or by external light cycles is unknown. We investigated the circadian and homeostatic regulation of hypocretin in the absence of environmental light cycles. To this purpose we performed repetitive samplings of cerebrospinal fluid in rats through implanted microcannulas in the cisterna magna and determined hypocretin-1 levels by radioimmunoassay. These experiments were also performed in rats that received a lesion of the suprachiasmatic nucleus (SCN), a major pacemaker for circadian rhythms in mammals. The results showed sustained rhythmicity of hypocretin in constant dim red light in control animals. SCN-lesioned animals showed no circadian rhythms in hypocretin and mean hypocretin levels were remarkably low. The results indicate that the SCN is indispensable for rhythmicity in hypocretin and induces a daily increase in hypocretin levels during the animal's active phase. Additional sleep deprivation experiments were carried out to investigate homeostatic regulation of hypocretin. Hypocretin levels increased in response to sleep deprivation in both control and SCN-lesioned animals, demonstrating that sleep homeostatic control of hypocretin occurs independently from the SCN. Our data indicate that the circadian pacemaker of the SCN and sleep homeostatic mechanisms converge on one single sleep regulatory substance.

Control of the estradiol-induced prolactin surge by the suprachiasmatic nucleus.

In the present study we investigated how the suprachiasmatic nucleus (SCN) controls the E(2)-induced PRL surge in female rats. First, the role of vasopressin (VP), a SCN transmitter present in medial preoptic area (MPO) projections and rhythmically released by SCN neurons, as a circadian signal for the E(2)-induced PRL surge was investigated. Using a reverse microdialysis technique, VP was administered in the MPO during the PRL surge, resulting in a suppression of the surge. VP administration before the surge did not affect PRL secretion. Also, administration of a V1a receptor antagonist before the surge was ineffective. Second, lesions of the SCN were made that resulted in constant basal PRL levels, suggesting that with removal of the SCN a stimulatory factor for PRL secretion disappeared. Indeed, the PRL secretory response to blockade of pituitary dopamine receptors was significantly reduced in SCN-lesioned animals. These data suggest that the afternoon decrease of VP release in the MPO by SCN terminals enables the PRL surge to occur, and may thus be a circadian signal for the PRL surge. Simultaneously the SCN is involved in the regulation of the secretory capacity of the pituitary, possibly via specific PRL-releasing factors.

Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway

In view of mounting evidence that the suprachiasmatic nucleus (SCN) is directly involved in the setting of sensitivity of the adrenal cortex to ACTH, the present study investigated possible anatomical and functional connections between SCN and adrenal. Transneuronal virus tracing from the adrenal revealed first order labelling in neurons in the intermedio-lateral column of the spinal cord that were shown to receive an input from oxytocin fibres and subsequently second-order labelling in neurons of the autonomic division of the paraventricular nucleus. The latter neurons were shown to receive an input from vasopressin or vasoactive intestinal peptide (VIP) containing SCN efferents. The true character of this SCN input to second-order neurons was also demonstrated by the fact that third-order labelling was present within the SCN, vasopressin or VIP neurons. The functional presence of the SCN-adrenal connection was demonstrated by a light-induced fast decrease in plasma corticosterone that could not be attributed to a decrease in ACTH. Using intact and SCN-lesioned animals, the immediate decrease in plasma corticosterone was only observed in intact animals and only at the beginning of the dark period. This fast decrease of corticosterone was accompanied by constant basal levels of blood adrenaline and noradrenaline, and is proposed to be due to a direct inhibition of the neuronal output to the adrenal cortex by light-mediated activation of SCN neurons. As a consequence, it is proposed that the SCN utilizes neuronal pathways to spread its time of the day message, not only to the pineal, but also to other organs, including the adrenal, utilizing the autonomic nervous system.

Effects of suprachiasmatic transplants on circadian rhythms of neuroendocrine function in golden hamsters.

Grafts of fetal tissue including the suprachiasmatic nucleus (SCN) of the hypothalamus restore locomotor rhythmicity to behaviorally arrhythmic, SCN-lesioned Syrian hamsters. We sought to determine whether such transplants also reinstate endocrine rhythms in SCN-lesioned hamsters. In Exp 1, SCN lesions interrupted estrous cycles in a 14 h light, 10 h dark photoperiod and locomotor rhythms in constant dim red light (DD). SCN grafts that reinstated behavioral circadian rhythms consistently failed to reestablish estrous cycles. After ovariectomy, estradiol implants triggered LH surges at approximately circadian time 8 in 10 of 12 brain-intact control females and 0 of 9 SCN-lesioned, grafted females. Daily rhythms of the principal urinary melatonin metabolite, 6alpha-sulfatoxymelatonin, were not reestablished by behaviorally functional grafts. In Exp 2, SCN lesions eliminated locomotor rhythmicity in adult male hamsters maintained in DD. Seven to 12 weeks after restoration of locomotor activity rhythms by fetal grafts, hosts and sham-lesioned controls were decapitated at circadian times 4, 8, 12, 16, 20, or 24. Clear circadian rhythms of both serum corticosterone and cortisol were seen in sham-lesioned males, with peaks in late subjective day. No circadian rhythms in either adrenal hormone were evident in serum from lesioned-grafted males. Testicular regression, observed in intact and sham-lesioned males maintained in DD, was absent not only in arrhythmic SCN-lesioned hamsters given grafts of cerebral cortex, but also in animals in which hypothalamic grafts had reinstated locomotor rhythmicity. The pineal melatonin concentration rose sharply during the late subjective night in control hamsters, but not in SCN-lesioned animals bearing behaviorally effective transplants. Even though circadian rhythms of locomotor activity are restored by SCN transplants, circadian endocrine rhythms are not reestablished. Endocrine rhythms may require qualitatively different or more extensive SCN outputs than those established by fetal grafts.

Behavior of SCN-lesioned chipmunks in natural habitat: a pilot study.

The necessity of a circadian pacemaker, the suprachiasmatic nuclei (SCN), for survival was evaluated in a population of approximately 65 wild eastern chipmunks, Tamias striatus. The research involved over 3000 h of field-work between May 1995 and October 1997 on a study site at Mountain Lake Biological Station, Virginia. The 28 chipmunks randomly designated as project animals included 10 SCN-lesioned chipmunks, 5 surgical controls (sham-lesioned), and 13 intact controls. Visual observation, live trapping, and radio telemetric tracking were used to assess 6 aspects of survival and reproduction. Upon release after surgery, every animal returned to its den site and was able to maintain its home territory. In warm months from May through October, all chipmunks were active above ground with a strictly day-active pattern. During the remaining cold months, they were normothermic but relatively torpid in their underground dens for extended periods of time. Short-term mortality for the initial 3 months included only a single intact control chipmunk; loss for the extended period from August 1995 to October 1996 was 40% for the SCN-lesioned animals, 0% for surgical controls, and 15.4% for the intact controls. Survival differences were not significant between surgical control and intact control groups but were significant (alpha = .10) between SCN-lesioned and pooled control groups. Annual body weight patterns were similar for both groups. Most individuals in both SCN-lesioned and control groups were reproductively active in the spring and fall breeding periods. Lack of major differences may be attributable to the exceptionally favorable conditions for survival such as a very abundant fall acorn crop, medium population size, and absence of heavy predation.

Restricted daytime feeding modifies suprachiasmatic nucleus vasopressin release in rats.

The authors have shown previously that vasopressin (VP) release from suprachiasmatic nucleus (SCN) efferents in rats is important for the timing of the circadian activity of the hypothalamo-pituitary-adrenal (HPA) axis, resulting in a circadian rise in corticosterone at dusk. When meals are supplied at a fixed time during the light period, however, this normal circadian activity of the HPA axis is strongly modified. Under such a restricted feeding regimen, a corticosterone peak appears just before the daily meal in addition to the circadian corticosterone peak at dusk. This feeding-associated rise in corticosterone is regarded as an SCN-independent circadian rhythm because it is sustained in SCN-lesioned animals. Despite these previous results, the authors investigated a putative involvement of SCN-derived VP in the control of the prefeeding corticosterone peak by measuring the intranuclear release of VP in the SCN and plasma corticosterone levels in rats in ad libitum feeding conditions as well as in animals that were obliged to feed during a 2-h period in the middle of the light period. Restricted daytime feeding caused clear changes in the daily release pattern of VP from SCN terminals. Both a delayed onset of the diurnal rise and a premature decline of the elevated daytime levels were observed, but the acrophase of the VP rhythm was not phase shifted. Concerning the circadian corticosterone peak, no phase shift of its acrophase was observed either. It is concluded that (1) restricted daytime feeding does affect SCN activity, (2) intranuclear release of VP within the SCN is an important mechanism to amplify and synchronize the circadian rhythms as dictated by the light/dark-entrained circadian pacemaker, and (3) VP release observed in animals on restricted feeding is completely compatible with the previously proposed inhibitory action of SCN-derived VP on the HPA axis.

Output Signals of the Scn

The suprachiasmatic nucleus (SCN) of the hypothalamus controls circadian rhythmicity in mammals (for reviews, see Refs. 33 and 59). Responses modulated by the SCN are numerous and include rhythms in sleep/wake cycles, locomotor, gnawing and general activity, temperature, ingestive behavior, and rhythms of hormonal and peptide secretions. Though a great deal is known about the neuroanatomical organization of the SCN, many elements of the structure-function relationships remain to be discovered. For example, it is not known which cellular components of the SCN function as driving pacemakers or which output signal(s) of these pacemakers are important for each of its functions. While some signals from pacemaker cells reach target regions by neural efferents, there is also evidence that rhythmic responses can be controlled by diffusible signals. This article reviews output signals from the SCN. The data available suggest that neural efferents are not necessary for the control of locomotor activity rhythms. Evidence that a diffusible signal is sufficient to restore activity rhythms in SCN-lesioned animals is described. Finally, possible physiological mechanisms for diffusible signals are suggested.

Clorgyline effect on pineal melatonin biosynthesis in rats with lesioned suprachiasmatic nuclei.

We have reported that clorgyline-induced stimulation of pineal melatonin biosynthesis could be augmented by the exposure to 24h of constant light in young but not in aged rats. Aging is associated with the declined integrity of the suprachiasmatic nuclei (SCN), the major station of the light signal passage from the retina to the pineal gland. The present study aimed to investigate whether SCN integrity is essential for clorgyline effects on pineal melatonin biosynthesis in light-primed rats. Clorgyline (2.5 mg/kg, s.c.) was administered to sham-operated and SCN-lesioned Sprague-Dawley rats kept under regular light/dark cycle or exposed to 24h of constant light. Pineal melatonin and related indoles were evaluated by HPLC-fluorimetric procedure. Clorgyline stimulated pineal melatonin biosynthesis in both SCN-lesioned and sham-operated rats kept under regular light/dark cycle. Exposure to constant light (for 24h) augmented clorgyline-induced stimulation of melatonin biosynthesis in sham-operated rats, but not in SCN-lesioned animals. The obtained results suggest that decline in SCN activity (e.g., age-associated) might contribute to previously reported attenuation of clorgyline-induced stimulation of melatonin biosynthesis in light-primed aged rats.

Effects of extremely low frequency (ELF) magnetic fields on circadian rhythm generated in suprachiasmatic nucleus

Circadian activity parameters of 53 white-tailed antelope ground squirrels, Ammospermophilus leucurus, were measured to determine the role of the suprachiasmatic nuclei (SCN) pacemaker in their health and survival. Wheel-running activity was monitored in the laboratory with 44 individuals to document the presence of free-running circadian rhythms and ability to entrain to light-dark cycles. Twenty-two individuals were returned to the desert site of origin, including 12 intact control animals and 10 animals whose circadian timing had been disrupted by SCN-lesioning. Time of activity was recorded continuously for 15 days in a large outdoor enclosure by a motion detector, a microchip transponder detector, and video surveillance. An unplanned nighttime attack by a feral cat resulted in the death of 60% of the SCN-lesioned animals and 29% of the control animals in the enclosure. Surface activity of SCN-lesioned animals at the food cache occurred both in daytime and at night, ranging from 16.0% nighttime activity for one partially lesioned individual to 52.1% for one completely lesioned animal. Controls were strongly day-active, with nighttime surface trips constituting only 0–1.3% of all excursions to the cache. Nine wild free-ranging individuals, including one with a radiotransmitter collar, were exclusively day-active. One of the functions of the SCN in mammals may be to reduce activity of animals during times that are unfavorable for activity.