@article{siopes_underwood_2008, title={Diurnal variation in the cellular and humoral immune responses of Japanese quail: Role of melatonin}, volume={158}, ISSN={["0016-6480"]}, DOI={10.1016/j.ygcen.2008.07.008}, abstractNote={Experiments were conducted to determine if diurnal variations occur in the cellular and humoral immune responses of sexually mature, male Japanese quail and if this diurnal variation is mediated by the daily rhythm of melatonin. In Experiment 1, quail were exposed to LD 12:12 light-dark cycles and immune responses were measured in response to a single antigenic challenge given to different groups every 4h over a 24h period. Diurnal changes occurred in both the cellular and humoral immune responses. The cellular response was higher during the light phase than during the dark phase whereas the opposite was true for the humoral immune response. Experiment 2 was designed to determine if melatonin mediated these diurnal immune responses. Quail were maintained in continuous light (LL) to suppress endogenous melatonin production and half of them were given melatonin in the drinking water for 12h each day for 2 weeks. Contrary to control quail, significant daily variations occurred in both the humoral and cellular immune responses of birds given melatonin. As in Experiment 1, the cellular and humoral immune responses were out of phase with one another, with the humoral response being maximal when melatonin was present. We may conclude that there exists a melatonin dependent diurnal variation in both cellular and humoral immune responses of quail. The responses were inverse to one another during the daily light-dark cycle with the cellular response being maximal during the daily light period and the humoral response being maximal during the daily dark period.}, number={3}, journal={GENERAL AND COMPARATIVE ENDOCRINOLOGY}, author={Siopes, T. D. and Underwood, H. A.}, year={2008}, month={Sep}, pages={245–249} }
 @article{steele_tosini_siopes_underwood_2006, title={Time keeping by the quail's eye: Cireadian regulation of melatonin production}, volume={145}, ISSN={["1095-6840"]}, DOI={10.1016/j.ygcen.2005.09.004}, abstractNote={Previous studies have shown that eye removal disrupts the circadian body temperature and activity rhythms of Japanese quail supporting the hypothesis that the eyes act as pacemakers within the quail circadian system. Furthermore, the putative ocular pacemakers are coupled to the rest of the circadian system via neural and hormonal outputs. Although the neural pathway has yet to be identified, experiments suggest that the daily rhythm of ocular melatonin synthesis and release is the hormonal output. We sought to strengthen the hypothesis that the eyes are the loci of circadian pacemakers, and that melatonin output is involved, by examining melatonin secretion in cultured quail retinas. Using an in vitro flow-through system we demonstrated that (1) isolated retinal tissue could exhibit a rhythm of melatonin release, (2) the rhythm of melatonin synthesis is directly entrainable by 24-h light–dark cycles, and (3) supplementation of the culture medium with serotonin is necessary for robust, rhythmic production of melatonin in constant darkness. These results show definitively that the eyes are the loci of a biological clock and, in light of previous studies showing the disruptive effects of blinding on the circadian system, strengthen the hypothesis that the ocular clock is a circadian pacemaker that can affect the rest of the circadian system via the cyclic synthesis and release of melatonin. The quail retina is proving to be a valuable in vitro model for investigating properties of circadian pacemakers.}, number={3}, journal={GENERAL AND COMPARATIVE ENDOCRINOLOGY}, author={Steele, CT and Tosini, G and Siopes, T and Underwood, H}, year={2006}, month={Feb}, pages={232–236} }
 @article{steele_zivkovic_siopes_underwood_2003, title={Ocular clocks are tightly coupled and act as pacemakers in the circadian system of Japanese quail}, volume={284}, ISSN={["0363-6119"]}, DOI={10.1152/ajpregu.00447.2002}, abstractNote={Our previous studies showed that the eyes of Japanese quail contain a biological clock that drives a daily rhythm of melatonin synthesis. Furthermore, we hypothesized that these ocular clocks are pacemakers because eye removal abolishes freerunning rhythms in constant darkness (DD). If the eyes are indeed acting as pacemakers, we predicted that the two ocular pacemakers in an individual bird must remain in phase in DD and, furthermore, the two ocular pacemakers would rapidly regain coupling after being forced out of phase. These predictions were confirmed by demonstrating that 1) the ocular melatonin rhythms of the two eyes maintained phase for at least 57 days in DD and 2) after ocular pacemakers were forced out of phase by alternately patching the eyes in constant light, two components of body temperature were observed that fused into a consolidated rhythm after 5–6 days in DD, showing pacemaker recoupling. The ability to maintain phase in DD and rapidly recouple after out-of-phase entrainment demonstrates that the eyes are strongly coupled pacemakers that work in synchrony to drive circadian rhythmicity in Japanese quail.}, number={1}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY}, author={Steele, CT and Zivkovic, BD and Siopes, T and Underwood, H}, year={2003}, month={Jan}, pages={R208–R218} }
 @article{moore_siopes_steele_underwood_2002, title={Pineal melatonin secretion, but not ocular melatonin secretion, is sufficient to maintain normal immune responses in Japanese quail (Coturnix coturnix japonica)}, volume={126}, ISSN={["0016-6480"]}, DOI={10.1016/S0016-6480(02)00011-4}, abstractNote={Reports that plasma melatonin is an important immune regulator in avian species have been rather sparse and contradictory. Also, the primary source of immune-modulating melatonin has yet to be determined in birds. In Japanese quail (Coturnix coturnix japonica), the pineal gland and eyes contribute roughly two thirds and one third of the melatonin found in the blood, respectively. Two experiments were conducted to evaluate melatonin as an immune modulator in Japanese quail and to determine the primary source of immune-modulating melatonin in this species. Experiment 1 was designed to evaluate the involvement of the pineal gland and the eyes in immunocompetence. Each of three groups of quail was assigned a surgical treatment and the cellular and humoral immune responses were determined 8 weeks following surgery. The surgical treatments were pinealectomy (Px), sham pinealectomy (SH-Px), and ocular enucleation (eye removal (Ex)). Experiment 2 utilized exogenous melatonin as a replacement to reconstitute immune responses in surgically immunocompromised birds. In this experiment, 50.0 microg/ml of melatonin, or diluent only, was provided to Px and SH-Px birds in the drinking water ad libitum. The cellular and humoral immune responses were determined after 8 weeks of melatonin treatment. In both experiments, a cutaneous basophil hypersensitivity reaction to phytohemagglutinin was measured to evaluate the cellular immune response. To evaluate the humoral immune response, primary antibody titers were determined 7 days postintravenous injection with a Chukar red blood cell suspension. Flow cytometric analysis of peripheral blood lymphocytes was performed to determine the relative percentage of CD4(+) and CD8(+) T- and B-lymphocytes in all treatments of Experiment 2. In Experiment 1, both the SH-Px and Ex surgical treatments produced similar cellular and humoral immune responses, and these responses were significantly greater than those in Px-treated birds. Pinealectomy significantly reduced the cellular and humoral immune responses from SH-Px by 25.8% and 41.3%, respectively. In Experiment 2, Px again resulted in depressed cellular and humoral immune responses. In addition, Px significantly reduced CD8(+) T-lymphocyte numbers compared to SH-Px, while B-lymphocytes remained unchanged. Melatonin administration to Px birds increased the cellular (32.9%) and humoral (30.6%) immune responses to the level of control (SH-Px) birds, although this reconstitution was not due to increased CD8(+) T- or B-lymphocytes. From these data, it was clear that removal of the pineal gland, but not the eyes, reduced cellular and humoral immune responses, which were reconstituted to normal levels by exogenous melatonin. These data suggest that immunodepression is only observed in birds with two thirds of the plasma melatonin removed by pinealectomy. Removal of one third of the plasma melatonin (by ocular enucleation) is not sufficient to reduce cellular and humoral responses in the Japanese quail.}, number={3}, journal={GENERAL AND COMPARATIVE ENDOCRINOLOGY}, author={Moore, CB and Siopes, TD and Steele, CT and Underwood, H}, year={2002}, month={May}, pages={352–358} }
 @article{underwood_steele_zivkovic_2001, title={Circadian organization and the role of the pineal in birds}, volume={53}, ISSN={["1097-0029"]}, DOI={10.1002/jemt.1068}, abstractNote={Abstract}, number={1}, journal={MICROSCOPY RESEARCH AND TECHNIQUE}, author={Underwood, H and Steele, CT and Zivkovic, B}, year={2001}, month={Apr}, pages={48–62} }
 @inbook{underwood_2001, title={Circadian organization in nonmammalian vertebrates}, ISBN={0306464896}, DOI={10.1007/978-1-4615-1201-1_6}, abstractNote={Remarkable progress has been made in the last quarter century in our knowledge of the concrete nature of biological clocks both at the levels of tissue and organs and at molecular levels. Studies in vertebrates have focused on the anatomic locations of sites involved in generating circadian rhythms, the ways these sites communicate with one another, and the ways that external stimuli, most notably light, affect the system. These studies have revealed a surprising complexity in the organization of circadian systems in nonmammalian vertebrates. Nonmammalian vertebrates are multioscillator in nature, that is, more than one circadian clock is involved in generating rhythmicity, and there are multiple photic input pathways as well. At least three sites have been shown to exhibit autonomous circadian rhythmicity: the pineal organ, the suprachiasmatic area of the hypothalamus, and the eyes. Circadian “organization” is accomplished by coupling together these rhythmic sites via hormonal and neural pathways so that the multiple clocks can act in a coherent fashion to drive the myriad overt rhythms that the organism possesses. In some cases, persistent rhythmicity in one site may require periodic inputs from another.}, booktitle={Handbook of behavioral neurobiology}, publisher={New York, NY: Kluwer Academic/Plenum Publ.}, author={Underwood, H.}, editor={E. M. Blass, N. T. Adler and King, F.Editors}, year={2001}, pages={111–140} }
 @article{zivkovic_underwood_siopes_2000, title={Circadian ovulatory rhythms in Japanese quail: Role of ocular and extraocular pacemakers}, volume={15}, ISSN={["0748-7304"]}, DOI={10.1177/074873040001500211}, abstractNote={ Previous studies have shown that the circadian system of Japanese quail is composed of multiple photic inputs and multiple oscillators. Among these are extraretinal photoreceptors that mediate both circadian and photoperiodic responses and circadian pacemakers in the eyes that, via neural and hormonal outputs, help to maintain rhythmicity of central circadian clocks (presumably located in the suprachiasmatic area of the hypothalamus). Furthermore, a component of the central circadian system is influenced by reproductive hormones. Under certain conditions, the circadian system of female quail can be induced to split into two circadian components: one driven by ocular pacemakers and one driven by feedback from reproductive hormones. Importantly, ovulation is either inhibited or permitted as these two oscillators (or sets of oscillators) constantly change internal phase relationships with each other, suggesting an “internal coincidence” mechanism in the control of ovulation. The oviposition patterns of quail in light-dark (LD) cycles also support an internal coincidence mechanism. The authors tested the hypothesis that the ocular pacemakers are an important component of an internal coincidence mechanism controlling ovulation by examining the effects of blinding by complete eye removal (EX), and the effects of eye-patching, on the body temperature and oviposition patterns of quail exposed to 24-h LD cycles. They also examined the effects of EX on quail exposed to continuous light (LL) and to continuous darkness (DD). Neither EX nor eyepatching affected the oviposition patterns of birds in LD. Furthermore, robust body temperature and oviposition rhythms continued in EX birds in LL, but body temperature became arrhythmic in DD with the cessation of ovulation. The results do not show a role for ocular pacemakers in the control of ovulation, but they do support the hypotheses that (1) entrainment of the central oscillators by extraretinally perceived light is sufficient to preserve a normal ovulatory pattern in LD in the absence of the ocular pacemakers, and (2) in LL, feedback of reproductive hormones onto the central oscillators is sufficient to organize the circadian system even in the absence of the ocular pacemakers. Whether or not the ocular pacemakers are normally involved in the control of ovulation is still an open question. }, number={2}, journal={JOURNAL OF BIOLOGICAL RHYTHMS}, author={Zivkovic, BD and Underwood, H and Siopes, T}, year={2000}, month={Apr}, pages={172–183} }
 @article{hyde_underwood_2000, title={Effects of melatonin administration on the circadian activity rhythm of the lizard Anolis carolinensis}, volume={71}, ISSN={["0031-9384"]}, DOI={10.1016/S0031-9384(00)00340-1}, abstractNote={The green anole, Anolis carolinensis, is the most thoroughly studied North American lizard species, yet little is known about the circadian system of this species. Studies in several lizard species, including Anolis, support the hypothesis that the pineal organ is the site of a major circadian pacemaker that controls the phasing and frequency of circadian clocks located elsewhere. We examined the effects of exogenous administration of the pineal hormone, melatonin, to determine if the pineal secretion of melatonin could be the mechanism whereby the pineal communicates with the rest of the circadian system in Anolis. Continuous melatonin administration via subcutaneous silastic implants to pineal-intact anoles exposed to light-dark (LD) cycles 6:18 and LD 6:20 and to pinealectomized anoles entrained to LD 6:18 completely suppressed activity that preceded lights-on suggesting a direct inhibitory (masking) effect on activity. Continuous exogenous administration of lower dosages of melatonin to anoles expressing their endogenous circadian activity rhythm (free-running) in dim continuous light caused either arrhythmicity, a shortening of the free-running period, bouts of arrhythmicity and rhythmicity, or a suppression of activity. It was concluded that melatonin can affect both the expression of the activity rhythm as well as the circadian oscillator driving the activity rhythm. The results support the hypothesis that the circadian pacemaker in the pineal organ controls other (subordinate) circadian clocks via the rhythmic synthesis and secretion of melatonin.}, number={1-2}, journal={PHYSIOLOGY & BEHAVIOR}, author={Hyde, LL and Underwood, H}, year={2000}, month={Oct}, pages={183–192} }
 @article{manglapus_iuvone_underwood_pierce_barlow_1999, title={Dopamine mediates circadian rhythms of rod-cone dominance in the Japanese quail retina}, volume={19}, DOI={10.1523/jneurosci.19-10-04132.1999}, abstractNote={A circadian clock modulates the functional organization of the Japanese quail retina. Under conditions of constant darkness, rods dominate electroretinogram (ERG) b-wave responses at night, and cones dominate them during the day, yielding a circadian rhythm in retinal sensitivity and rod–cone dominance. The activity of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, also exhibits a circadian rhythm in the retina with approximately threefold higher levels during the day than at night. The rhythm of tyrosine hydroxylase activity is opposite in phase to the circadian activity of tryptophan hydroxylase, the first enzyme in the melatonin biosynthetic pathway. We tested whether dopamine may be related to the physiological rhythms of the retina by examining the actions of pharmacological agents that effect dopamine receptors. We found that blocking dopamine D2 receptors in the retina during the day mimics the nighttime state by increasing the amplitude of the b-wave and shifting the retina to rod dominance. Conversely, activating D2 receptors at night mimics the daytime state by decreasing the amplitude of the b-wave and shifting the retina to cone dominance. A selective antagonist for D1 dopamine receptors has no effect on retinal sensitivity or rod–cone dominance. Reducing retinal dopamine partially abolishes rhythms in sensitivity and yields a rod-dominated retina regardless of the time of day. These results suggest that dopamine, under the control of a circadian oscillator, has a key role in modulating sensitivity and rod–cone dominance in the Japanese quail retina.}, number={10}, journal={Journal of Neuroscience}, author={Manglapus, M. K. and Iuvone, P. M. and Underwood, H. and Pierce, M. E. and Barlow, R. B.}, year={1999}, pages={4132–4141} }
 @article{underwood_steele_zivkovic_1999, title={Effects of fasting on the circadian body temperature rhythm of Japanese quail}, volume={66}, ISSN={["0031-9384"]}, DOI={10.1016/S0031-9384(98)00287-X}, abstractNote={The effect of food deprivation on the body temperature and activity rhythms of quail was assessed in birds exposed to both light–dark (LD) cycles and to continuous darkness (DD). Quail normally exhibit a daily rhythm of body temperature in LD that will persist in DD (that is, the rhythm is circadian). In LD, 3 days’ food deprivation caused the body temperature to drop below its normal nighttime levels, whereas daytime body temperature was unaffected. In DD, food deprivation caused the body temperature to drop below normal at all phases of the circadian rhythm of body temperature. Accordingly, the lack of hypothermia during the light phase of the LD cycle following food deprivation must represent a direct exogenous or “masking” effect of light, and is not an endogenous property of the circadian system. Blind birds exposed to LD 12:12 exhibited an entrained body temperature rhythm, and food deprivation caused a drop in body temperature below normal levels during both the light and dark phases of the LD cycle. Accordingly, the masking effects of light observed in normal birds on LD cycles is mediated via retinal photoreceptors and not via extraretinal photoreceptors. Measurements of activity levels before and during fasting indicate that fasting-induced hypothermia cannot be explained simply as a consequence of decreases in activity levels. Food deprivation was also observed to cause significant phase shifts in the endogenous rhythm of body temperature.}, number={1}, journal={PHYSIOLOGY & BEHAVIOR}, author={Underwood, H and Steele, CT and Zivkovic, B}, year={1999}, month={Mar}, pages={137–143} }
 @article{zivkovic_underwood_steele_edmonds_1999, title={Formal properties of the circadian and photoperiodic systems of Japanese quail: Phase response curve and effects of T-cycles}, volume={14}, ISSN={["0748-7304"]}, DOI={10.1177/074873099129000786}, abstractNote={ A role for the circadian system in photoperiodic time measurement in Japanese quail is controversial. The authors undertook studies of the circadian and photoperiodic system of Japanese quail to try to identify a role for the circadian system in photoperiodic time measurement. The circadian studies showed that the circadian system acts like a low-amplitude oscillator: It is readily reset by light without significant transients, has a Type 0 phase response curve (PRC), and has a large range of entrainment. In fact, a cycle length that is often used in resonance protocols (LD 6:30) is within the range of entrainment. The authors employed T-cycle experiments; that is, LD cycles with 6-and 14-h photoperiods and period lengths ranging from 18 to 36 h to test for circadian involvement in photoperiodic time measurement. The results did not give evidence for circadian involvement in photoperiodic time measurement: T-cycles utilizing 6-h photoperiods were uniformly noninductive (that is, did not stimulate the reproductive system), whereas T-cycles utilizing 14-h photoperiods were inductive (stimulatory). A good match was observed between the phase-angles exhibited on the T-cycles employing 6-h photoperiods and the predicted phase-angles calculated from a PRC generated from 6-h light pulses. }, number={5}, journal={JOURNAL OF BIOLOGICAL RHYTHMS}, author={Zivkovic, BD and Underwood, H and Steele, CT and Edmonds, K}, year={1999}, month={Oct}, pages={378–390} }
 @inbook{underwood_wassmer_page_1997, title={Daily and seasonal rhythms}, booktitle={Comparative Physiology (v. 2, ch. 24). Handbook of physiology, Section 13}, publisher={New York: Published for the American Physiological Society by Oxford University Press}, author={Underwood, H. and Wassmer, G. and Page, T.}, year={1997}, pages={1653–1763} }
 @article{underwood_siopes_edmonds_1997, title={Eye and gonad: Role in the dual-oscillator circadian system of female Japanese quail}, volume={272}, ISSN={["0363-6119"]}, DOI={10.1152/ajpregu.1997.272.1.r172}, abstractNote={ Experiments were conducted to determine the anatomic and physiological basis of the dual-oscillator circadian system of female Japanese quail. After blocking of ocular light perception by eye-patching, the circadian body temperature rhythm dissociates into two circadian components in continuous lighting (LL). One component free runs with a period significantly shorter than 24 h [mean period (tau) = 22.7 h] and is driven by an ocular pacemaker, whereas the other component free runs with a period significantly longer than 24 h (tau = 26.3 h). The long free-running rhythm is driven by the same circadian clock that drives the circadian rhythm of ovulation. The expression of the long free-running rhythm in LL depends on the presence of the ovary: body temperature rhythmicity is abolished by ovariectomy. The two free-running oscillators in eye-patched birds showed evidence of mutual interaction. Significantly, the phase relationships that occur as the two oscillators interact can determine whether or not ovulation occurs. The results are discussed in terms of an "internal coincidence" mechanism for photoperiodic time measurement. }, number={1}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY}, author={Underwood, H and Siopes, T and Edmonds, K}, year={1997}, month={Jan}, pages={R172–R182} }
 @article{underwood_siopes_1985, title={MELATONIN RHYTHMS IN QUAIL - REGULATION BY PHOTOPERIOD AND CIRCADIAN PACEMAKERS}, volume={2}, ISSN={["0742-3098"]}, DOI={10.1111/j.1600-079X.1985.tb00634.x}, abstractNote={The profile of melatonin in the eyes, pineal, and blood of Japanese quail was assessed in birds held under LD 16:8 and LD 6: 18 photoperiods. Melatonin levels in all three tissues showed a robust daily rhythm with higher levels occurring at night. The amplitude of the rhythm was depressed and its duration lengthened on LD 6: 18 relative to LD 16:8. The blood melatonin rhythm precisely reflected the rhythms shown by the pineal and eyes, supporting the idea that the blood rhythm is a result of melatonin secretion by both the eyes and pineal.}, number={2}, journal={JOURNAL OF PINEAL RESEARCH}, author={UNDERWOOD, H and SIOPES, T}, year={1985}, pages={133–143} }
 @article{underwood_whitsett_obrien_1985, title={PHOTOPERIODIC TIME MEASUREMENT IN THE MALE DEER MOUSE, PEROMYSCUS-MANICULATUS}, volume={32}, ISSN={["0006-3363"]}, DOI={10.1095/biolreprod32.4.947}, abstractNote={Weanling male deer mice, Peromyscus maniculatus, were exposed for three weeks either to light-dark (LD) cycles with periods (T=L+D) ranging from T=23 (1L:22D) to T=25.16 (1L:24.16D) or to 24-h LD cycles with photoperiods ranging from 1 (1L:23D) to 19 (19L:5D) h. Both the circadian locomotor activity rhythms and the response of the reproductive system to these LD cycles were assessed. The results demonstrate that the photoperiodic effectiveness of light depends on the phase of the light relative to the animal's circadian system, as marked by the circadian activity rhythm. Light falling during the animal's subjective night, from activity onset to at least 11.8 h after activity onset, stimulates growth and maturation of the reproductive system, whereas light falling during the rest of the circadian cycle is nonstimulatory.}, number={4}, journal={BIOLOGY OF REPRODUCTION}, author={UNDERWOOD, H and WHITSETT, JM and OBRIEN, TG}, year={1985}, pages={947–956} }