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A neural theory of circadian rhythms: The gated pacemaker

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Abstract

This article describes a behaviorally, physiologically, and anatomically predictive model of how circadian rhythms are generated by each suprachiasmatic nucleus (SCN) of the mammalian hypothalamus. This gated pacemaker model is defined in terms of competing on-cell off-cell populations whose positive feedback signals are gated by slowly accumulating chemical transmitter substances. These components have also been used to model other hypothalamic circuits, notably the eating circuit. A parametric analysis of the types of oscillations supported by the model is presented. The complementary reactions to light of diurnal and nocturnal mammals as well as their similar phase response curves are obtained. The “dead zone” of the phase response curve during the subjective day of a noctural rodent is also explained. Oscillations are suppressed by high intensities of steady light. Operations that alter the parameters of the model transmitters can phase shift or otherwise change its circadian oscillation. Effects of ablation and hormones on model oscillations are summarized. Observed oscillations include regular periodic solutions, periodic plateau solutions, rippled plateau solutions, period doubling solutions, slow modulation of oscillations over a period of months, and repeating sequences of oscillation clusters. The model period increases inversely with the transmitter accumulation rate but is insensitive to other parameter choices except near the breakdown of oscillations. The model's clocklike nature is thus a mathematical property rather than a formal postulate. A singular perturbation approach to the model's analysis is described.

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References

  • Aschoff, J.: Influences of internal and external factors on the period measured in constant conditions. Z. Tierpsychol. 49, 255–249 (1979)

    Google Scholar 

  • Carpenter, G.A.: A geometric approach to singular perturbation problems with applications to nerve impulse equations. J. Diff. Eqs. 23, 335–367 (1977a)

    Google Scholar 

  • Carpenter, G.A.: Periodic solutions of nerve impulse equations. J. Math. Anal. Appl. 58, 152–173 (1977b)

    Google Scholar 

  • Carpenter, G.A., Grossberg, S.: Adaptation and transmitter gating in vertebrate photoreceptors. J. Theor. Neurobiol. 1, 1–42 (1981)

    Google Scholar 

  • Carpenter, G.A., Grossberg, S.: Dynamic models of neural systems: Propagated signals, photoreceptor transduction, and circadian rhythms. In: Oscillations in mathematical biology. Grissell, R., Hodgson, J.P.E., Yanowich, M. (eds.). Berlin, Heidelberg, New York: Springer 1983a

    Google Scholar 

  • Carpenter, G.A., Grossberg, S.: A neural theory of circadian rhythms: split rhythms, long-term after-effects, and Aschoff's rule (in preparation) (1983b)

  • Daan, S., Pittendrigh, C.S.: A functional analysis of circadian pacemakers in nocturnal rodents. II. The variability of phase response curves. J. Comp. Physiol. 106, 253–266 (1976)

    Google Scholar 

  • DeCoursey, P.J.: Phase control of activity in a rodent. Cold Spring Harbor Symp. Quant. Biol. 25, 49–55 (1960)

    Google Scholar 

  • Earnest, D., Turek, F.W.: Splitting of the circadian rhythm of activity in hamsters: effects of exposure to constant darkness and subsequent re-exposure to constant light. J. Comp. Physiol. 145, 405–411 (1982)

    Google Scholar 

  • FitzHugh, R.: Impulses and physiological states in theoretical models of nerve membrane. Biophys. J. 1, 445–466 (1961)

    Google Scholar 

  • Grossberg, S.: Some physiological and biochemical consequences of psychological postulates. Proc. Natl. Acad. Sci. 60, 758–765 (1968)

    Google Scholar 

  • Grossberg, S.: Competition, decision, and consensus. J. Math. Anal. Appl. 66, 470–493 (1978)

    Google Scholar 

  • Grossberg, S.: How does a brain build a cognitive code? Psychol. Rev. 87, 1–51 (1980)

    Google Scholar 

  • Grossberg, S.: Psychophysiological substrates of schedule interactions and behavioral contrast. In: Mathematical psychology and psychophysiology. Grossberg, S. (ed.). Providence, R.I.: American Mathematical Society 1981

    Google Scholar 

  • Grossberg, S.: The processing of expected and unexpected events during conditioning and attention: a psychophysiological theory. Psychol. Rev. 89, 529–572 (1982a)

    Google Scholar 

  • Grossberg, S.: Studies of mind and brain: Neural principles of learning, perception, development, cognition, and motor control. Boston: Reidel 1982b

    Google Scholar 

  • Grossberg, S.: Some psychophysiological and pharmacological correlates of a developmental, cognitive, and motivational theory. In: Brain and information: evoked potential correlates. Karrer, R., Cohen, J., Tueting, P. (eds.). New York: New York Academy of Sciences 1983a

    Google Scholar 

  • Grossberg, S.: The quantized geometry of visual space: the coherent computation of depth, form, and lightness. Behav. Brain Sci. (1983b) (in press)

  • Gwinner, E.: Testosterone induces “splitting” of circadian locomotor activity rhythm in birds. Science 185, 72–74 (1974)

    Google Scholar 

  • Hodgkin, A.L.: The conduction of the nervous impulse. Liverpool: Liverpool University 1964

    Google Scholar 

  • Hodgkin, A.L., Huxley, A.F.: A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. 117, 500–544 (1952)

    Google Scholar 

  • Hoffman, K.: Splitting of the circadian rhythm as a function of light intensity. In: Biochronometry. Menaker, M. (ed.). Washington, D.C.: National Academy of Sciences 1971, pp. 134–150

    Google Scholar 

  • Jouvet, M., Mouret, J., Chouvet, G., Siffre, M.: Toward a 48-h day: experimental bicircadian rhythm in man. In: Circadian oscillations and organization in nervous systems. Pittendrigh, C.S. (ed.). Cambridge, MA: MIT Press 1974, pp. 491–497

    Google Scholar 

  • Kafka, M.S., Wirz-Justice, A., Naber, D., Marangos, P.J., O'Donohue, T.L., Wehr, T.A.: Effect of lithium on circadian neurotransmitter receptor rhythms. Neuropsychobiol. 8, 41–50 (1982)

    Google Scholar 

  • Kafka, M.S., Wirz-Justice, A., Naber, D., Circadian and seasonal rhythms in α- and β-adrenergic receptors in the rat brain. Brain Res. 207, 409–419 (1981)

    Google Scholar 

  • Kafka, M.S., Wirz-Justice, A., Naber, D., Wehr, T.A.: Circadian acetylcholine receptor rhythm in rat brain and its modification by imipramine. Neuropharmacol. 20, 421–425 (1981)

    Google Scholar 

  • Katz, B.: Nerve, muscle, and synapse. New York: McGraw-Hill 1966

    Google Scholar 

  • Kawato, M., Suzuki, R.: Two coupled neural oscillators as a model of the circadian pacemaker. J. Theor. Biol. 86, 547–575 (1980)

    Google Scholar 

  • Kramm, K.R.: Circadian activity in the antelope ground squirrel, Ammospermophilus leucurus. Ph. D. Thesis, University of California, Irvine 1971

  • Kronauer, R.E., Czeisler, C.A., Pilato, S.F., Moore-Ede, M.C., Weitzman, E.D.: Mathematical model of the human circadian system with two interacting oscillators. Am. J. Physiol. 242, R3-R17 (1982)

    Google Scholar 

  • Kuffler, S.W., Nicholls, J.G.: From neuron to brain. Sunderland, M.A.: Sinauer 1976

    Google Scholar 

  • Moore, R.Y.: Retinohypothalamic projection in mammals: a comparative study. Brain Res. 49, 403–409 (1973)

    Google Scholar 

  • Moore, R.Y.: Visual pathways and the central neural control of diurnal rhythms. In: Circadian oscillations and organization in nervous systems. Pittendrigh, C.S. (ed.). Cambridge, MA.: MIT Press 1974, pp. 537–542

    Google Scholar 

  • Moore-Ede, M.C., Sulzman, F.M., Fuller, C.A.: The clocks that time us. Cambridge, MA.: Harvard University Press 1982

    Google Scholar 

  • Naber, D., Wirz-Justice, A., Kafka, M.S.: Circadian rhythm in rat brain opiate receptor. Neurosci. Lett. 21, 45–50 (1981

    Google Scholar 

  • Nagumo, J., Arimoto, S., Yoshizawa, S.: An active pulse transmission line simulating nerve axon. Proc. I.E.E.E. 50, 2061–2070 (1962)

    Google Scholar 

  • Olds, J.: Drives and reinforcements: behavioral studies of hypothalamic functions. New York: Raven Press 1977

    Google Scholar 

  • Pickard, G.E., Turek, F.W.: Splitting of the circadian rhythm of activity is abolished by unilateral lesions of the suprachiasmatic nuclei. Science 215, 1119–1121 (1982)

    Google Scholar 

  • Pittendrigh, C.S.: Circadian rhythms and the circadian organization of living systems. Cold Spring Harbor Symp. Quant. Biol. 25, 159–185 (1960)

    Google Scholar 

  • Pittendrigh, C.S.: Circadian oscillations in cells and the circadian organization of multicellular systems. In: Circadian oscillations and organization in nervous systems. Pittendrigh, C.S. (ed.). Cambridge, MA.: MIT Press 1964, pp. 437–458

    Google Scholar 

  • Plonsey, R.: Bioelectric phenomena. New York: McGraw-Hill 1969

    Google Scholar 

  • Pohl, H.: Characteristics and variability in entrainment of circadian rhythms in light in diurnal rodents. In: Vertebrate circadian systems. Aschoff, J., Daan, S., Groos, G.A. (eds.). Berlin, Heidelberg, New York: Springer 1982, pp. 339–346

    Google Scholar 

  • Rosenwasser, A.M., Boulos, Z., Terman, M.: Circadian organization of food intake and meal patterns in the rat. Physiol. Behav. 27, 33–39 (1981)

    Google Scholar 

  • Sisk, C.L., Turek, F.W.: Role of the inter-connections of the suprachiasmatic nuclei in the hamster circadian system. Soc. Neurosci. Abstr. 8, 35 (1982)

    Google Scholar 

  • Wehr, T.A., Wirz-Justice, A.: Circadian rhythm mechanisms in affective illness and antidepressant drug action. Pharmacopsychiat. 15, 30–38 (1982)

    Google Scholar 

  • Wehr, T.A., Wirz-Justice, A., Goodwin, F.K., Duncan, W., Gillin, J.C.: Phase advance of the circadian sleep-wake cycle as an antidepressant. Science 206, 710–713 (1979)

    Google Scholar 

  • Wever, R.A.: The circadian system of man: results of experiments under temporal isolation. Berlin, Heidelberg, New York: Springer 1979

    Google Scholar 

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Supported in part by the Air Force Office of Scientific Research (AFOSR 82-0148), the National Science Foundation (NSF MCS-82-07778), the Northeastern University Research and Scholarship Development Fund, and the Office of Naval Research (ONR-N00014-83-K0337)

Supported in part by the Air Force Office of Scientific Research (AFOSR 82-0148), the National Science Foundation (NSF IST-80-00257), and the Office of Naval Research (ONR-N00014-83-K0337)

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Carpenter, G.A., Grossberg, S. A neural theory of circadian rhythms: The gated pacemaker. Biol. Cybern. 48, 35–59 (1983). https://doi.org/10.1007/BF00336883

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  • DOI: https://doi.org/10.1007/BF00336883

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