1. In the first part of the paper, the model of non-parametric entrainment of circadian pacemakers is tested for the case of nocturnal rodents. The model makes use of the available data on freerunning period (τ) in constant darkness and on phase response curves (PRC) for short light pulses. It is tested in experiments using 1 or 2 light pulses per cycle. 2. Mesocricetus auratus and Peromyscus leucopus entrain to Zeitgebers involving 1 pulse (15' or 60') per cycle. The phase angle differences between rhythm and light cycle depends on the periods (τ and T) as predicted by the model. Entrainment of P. leucopus is unstable due to the after effects on τ created by the light pulse. 3. The limiting values of Zeitgeber period to which the animals entrain are much closer to 24 h than in Drosophila pseudoobscura, as the model predicts. However, frequent failures to entrain to T = 23 and T = 25 h are only explained if we take considerable interindividual variation in both τ and PRC into account. 4. With 2 pulses per cycle, the model predicts that entrainment will be more stable when activity is in the longer interval between the pulses than when it is in the shorter interval. This is true in the experimental data, where the phase relationships match predictions for skeleton photoperiods up to ca. 14 h. Increasing asymmetry forces animals into a "phase jump", so that activity shifts from the shorter to the longer interval. These ψ-jumps are accurately predicted in the hamster, but they occur at much longer photoperiods than predicted in P. leucopus. 5. Thus, the unqualified model, using a rigidly fixed species τ and PRC, is surely inadequate to explain entrainment. The extent to which variations in τ and PRC-shape, both "spontaneous" and induced by the entrainment process, can be known or inferred restricts the validity of the predictions. Yet we conclude, from a good deal of agreement between experiment and prediction (i), from the close correspondence between complete and skeleton photoperiods (ii), and on behavioural grounds (iii), that non-parametric entrainment by short light signals has a major share in the entrainment of nocturnal rodent rhythms in nature. 6. With these restrictions in mind, we analyse in the second part of the paper how the empirical regularities concerning τ and PRC contribute to the stabilization of the phase angle difference (ψ) between the pacemaker and the external world. Use is made of computer simulations of artificial pacemakers with variable τ and PRC. 7. ψ is most sensitive to instabilities in τ when ¯τ is close to 24 h. Thus the very circadian nature of these pacemakers helps to conserve ψ. Selection pressure for homeostasis of τ has been large in a species (M. auratus) where ¯τ = 24 h. The effect of ψ-instability is further reduced by entrainment with 2 pulses (dawn and dusk), made possible by the PRC's having both an advance and a delay section. 8. To analyze the contributions to ψ-conservation with seasonally changing photoperiod, we have assumed that it is of functional significance to conserve the phase of activity with respect to dusk (nocturnal animals) or to dawn (diurnal animals). We distinguish three contributions of nocturnal pacemaker behaviour to this type of ψ-conservation: increased amplitude of the PRC (i), asymmetry in the PRC, such that the slope of the delay-part is steeper than the slope of the advance-part (ii), and a short freerunning period in DD (iii). 9. A further contribution must derive from parametric effects of light, which are not traceable by the model, but certainly effective in preventing in complete photoperiods the ψ-jump which is seen in skeleton photoperiods. The existence of parametric effects is further demonstrated by the change of τ with light intensity in LL, described by Aschoffs Rule, which presumably reflects differences in PRC-shape between nocturnal and diurnal animals. 10. The paper concludes with an attempt to distinguish the features of circadian clocks that are analytically necessary for entrainment to occur (i), or have functional meaning, either in the measurement of the lapse of time (ii) or in the identification of local time (iii).

/pdf/a-functional-analysis-of-circadian-pacemakers-in-nocturnal-4uu8zk2j0m.pdf

A Functional Analysis of Circadian Pacemakers in Nocturnal Rodents. I. The Stability and Lability of Spontaneous Frequency

The concept of 'sleeping on a problem' is familiar to most of us. But with myriad stages of sleep, forms of memory and processes of memory encoding and consolidation, sorting out how sleep contributes to memory has been anything but straightforward. Nevertheless, converging evidence, from the molecular to the phenomenological, leaves little doubt that offline memory reprocessing during sleep is an important component of how our memories are formed and ultimately shaped.

Sleep-dependent memory consolidation

1

Phase response curves for 15′ bright light pulses of four species of nocturnal rodents are described. All show delay phase shifts early in the subjective night, advance shifts in the late subjective night, and relative insensitivity during the subjective day.




2

The broad scatter in measured phase-shifts is largely due to error of measurement: the response of the pacemakers to light stimuli is more accurate than we observe.




3.

Indications are found that the response to a resetting stimulus at a given phase of the rhythm is correlated with the individual\(\bar \tau \) (freerunning period). Fast pacemakers (short\(\bar \tau \)) tend to be more delayed or less advanced by the light than slow pacemakers (long\(\bar \tau \)).




4.

Within individual mice (Mus musculus) the circadian pacemaker adjusts its resetting response to variations in its frequency: when τ is long (induced as after-effect of prior light treatment) light pulses at a defined phase of the oscillation (ct 15) produce smaller delay phase shifts than when τ is short.




5.

Among species there are conspicuous differences in the shape of the phase response curve: where\(\bar \tau \) is long, advance phase shifts are large and delay phase shifts small (Mesocricetus auratus); where\(\bar \tau \) is short, advance shifts are small, and delay shifts are large (Mus musculus;Peromyscus maniculatus).




6.

The functional meaning of the interrelationships of τ and PRC is briefly discussed.

A functional analysis of circadian pacemakers in nocturnal rodents

In men, high levels of endogenous testosterone (T) seem to encourage behavior intended to dominate - to enhance one's status over - other people. Sometimes dominant behavior is aggressive, its apparent intent being to inflict harm on another person, but often dominance is expressed nonaggressively. Sometimes dominant behavior takes the form of antisocial behavior, including rebellion against authority and law breaking. Measurement of T at a single point in time, presumably indicative of a man's basal T level, predicts many of these dominant or antisocial behaviors. T not only affects behavior but also responds to it. The act of competing for dominant status affects male T levels in two ways. First, T rises in the face of a challenge, as if it were an anticipatory response to impending competition. Second, after the competition, T rises in winners and declines in losers. Thus, there is a reciprocity between T and dominance behavior, each affecting the other. We contrast a reciprocal model, in which T level is variable, acting as both a cause and effect of behavior, with a basal model, in which T level is assumed to be a persistent trait that influences behavior. An unusual data set on Air Force veterans, in which data were collected four times over a decade, enables us to compare the basal and reciprocal models as explanations for the relationship between T and divorce. We discuss sociological implications of these models.

https://users.ox.ac.uk/~kgroup/publications/pdf/kacelnik_norris_1998_bbs_testosterone.pdf

Testosterone and dominance in men.

The experimental work described tested the prosposition that the suprachiasmatic nucleus of the hypothalamus is an autonomous circadian pacemaker. Simultaneous recording from two extracellular electrodes indicated neural (multiple unit) activity at two sites in the brain, one of which is in or near the suprachiasmatic nucleus and the other in one of many other brain locations. Both sites in intact rats displayed clear circadian rhythmicity of spontaneous neural activity. In experimental animals, a Halasz knife was used to create an island of hypothalamic tissue that contained the suprachiasmatic nuclei. In such animals that were also blinded by bilateral ocular enucleation, circadian rhythmicity was lost at all brain locations recorded outside the island, but it persisted within the island that contained the suprachiasmatic nuclei. The rhythmicity of the island is thus not dependent on afferent inputs from elsewhere in the brain.

https://www.pnas.org/content/pnas/76/11/5962.full.pdf

Persistence of circadian rhythmicity in a mammalian hypothalamic "island" containing the suprachiasmatic nucleus

Despite the widespread use of androgen in the treatment of hypogonadal men, its efficacy in restoring sexual behavior to hypogonadal patients has not been established in appropriately controlled behavioral studies. Accordingly, testosterone enanthate or vehicle was injected once every 4 weeks im in a double blind experiment. The subjects were six adult males, aged 32–65 yr, two with gonadal failure and four with secondary hypogonadism. Two doses of testosterone (100 and 400 mg) were administered for approximately 5 months, with the treatments varied at random within and among subjects. Details of sexual activity and experience were followed by the use of daily logs. Frequencies of erections, including nocturnal erections and coitus, showed significant dose-related responses to androgen treatment which closely followed the fluctuations in the circulating testosterone level. As indicated by the Profile of Mood States test, behavioral responses did not appear to be mediated by changes in mood. We co...

Effects of androgen on sexual behavior in hypogonadal men.

The relationship between circulating testosterone levels and male sexual behavior in rats

Castration of mice in freerunning conditions (total darkness, DD) causes a reduction of running wheel activity in the beginning of the active period (alpha) and stimulates activity at the end of alpha. Simultaneously, the period (tau) of the freerunning rhythm is increased. Both effects are abolished by implantation of a Silastic capsule from which a physiological dose of testosterone is released at a constant rate. The results are tentatively explained by differential endocrine influences on two oscillating components in the pacemaker of the circadian activity rhythm.

/pdf/an-effect-of-castration-and-testosterone-replacement-on-a-f86lwbs96c.pdf

An effect of castration and testosterone replacement on a circadian pacemaker in mice (Mus musculus)

Chapter 9 – Hormone Administration: Peripheral and Intracranial Implants1

Yohimbine hydrochloride, an alpha 2-adrenoceptor antagonist, increased sexual motivation in male rats as evidenced by increased mounting performance in mating tests conducted after genital anesthetization, increased percentage of male rats ejaculating in their first heterosexual encounter, and induction of copulatory behavior in sexually inactive male rats. These observations lead to the suggestion that alpha-adrenoceptors are important modulators of sexual arousal in intact male rats. These results indicate that pharmacological treatment of sexual (libido) dysfunction may be useful.

https://science.sciencemag.org/content/sci/225/4664/847.full.pdf

Erla R. Smith

Papers

Effects of androgen on sexual behavior in hypogonadal men.

The relationship between circulating testosterone levels and male sexual behavior in rats

An effect of castration and testosterone replacement on a circadian pacemaker in mice (Mus musculus)

Chapter 9 – Hormone Administration: Peripheral and Intracranial Implants1

Enhancement of sexual motivation in male rats by yohimbine.