Mutual interactions between optic lobe circadian pacemakers in the cricket Gryllus bimaculatus

The coupling mechanism between the bilaterally paired optic lobe circadian pacemakers in the cricket Gryllus bimaculatus was investigated by recording locomotor activity, under constant light or constant red light, after the optic nerve was unilaterally severed.

Developmental and genetic mosaic analysis of Drosophila m-dy mutants: Tissue foci for behavioral and morphogenetic defects

Mutants of the Drosophila miniature-dusky (m-dy) gene complex display morphogenetic phenotypes (miniature or dusky) caused by a change in the size and/or shape of the epidermal cells comprising the adult wing. In addition to a dusky phenotype, certain Andante-type mutants also exhibit lengthened circadian periods for two different behavioral rhythms. If the latter phenotype results from a direct effect on the circadian pacemaker, the Andante function should be required within the brain. In order to define the tissues that require the morphogenetic and behavioral functions, we have carried out a genetic mosaic analysis. This study demonstrates that normal wing morphogenesis is entirely dependent on the genotype of wing cells. Furthermore, temperature-shift experiments with a temperature-sensitive dy mutant indicate that the morphogenetic function is required during adult development, and after the cessation of wing epidermal cell proliferation. At this time in development, a columnar epithelium in the developing wing becomes flattened into the mature wing blade, and we postulate that the cell-size defect of m-dy mutants results from an alteration of this mor-phogenetic process. In contrast to the wing mor-phogenesis phenotype, the characterization of locomotor activity in mosaic adults revealed a strong correlation between the head genotype and the Andante circadian-period phenotype. This result indicates that neural tissues mediate the rhythm function. Thus, the behavioral and morphogenetic functions require gene expression in distinct tissues. Furthermore, the behavioral results are consistent with a requirement for Andante function within circadian pacemaker neurons. © 1995 Wiley-Liss, Inc.     

Differential effects of dihydrotestosterone and estrogen on the development of motoneuron morphology in a sexually dimorphic rat spinal nucleus

The rat lumbar spinal cord contains a sexually dimorphic motor nucleus, the spinal nucleus of the bulbocavernosus (SNB), whose motoneurons innnervate perineal muscles involved in copulatory reflexes. Dendritic development of SNB motoneurons is biphasic and androgen dependent. During the first 4 postnatal weeks, SNB dendrites grow exuberantly, and subsequently retract to mature lengths by 7 weeks of age. After early postnatal castration, SNB dendrites fail to grow, and testosterone replacement restores this growth. In other systems, testosterone and its metabolites, dihydrotestosterone and estrogen, are important for somatic and neural sexual differentiation. The purpose of the present study was to examine the effects of castration and dihydrotestosterone or estrogen replacement on the growth of SNB motoneuron somata and dendritic arbors. Male rat pups were castrated on postnatal (P) day 7 and treated daily with either dihydrotestosterone propionate (DHTP; 2 mg) or estradiol benzoate (EB; 100 μg) until P28 or P49. By using cholera toxin horseradish peroxidase (BHRP) histochemistry, the soma size, dendritic length, dendritic extent, and arbor area of BHRP-labeled SNB motoneurons were measured and analyzed. Both DHTP and EB treatment supported the initial exuberant growth of SNB dendrites through P28, but EB treatment was ineffective in maintaining mature, adult lengths at P49. The possible sites of hormone action and functional implications of these hormonal treatments are discussed. 1994 John Wiley & Sons, Inc.     

DEVELOPMENTAL MUTANTS OF VOLVOX: DOES MUTATION RECREATE THE PATTERNS OF PHYLOGENETIC DIVERSITY?

The nature of the variation which is created by mutation can show how the direction of evolution is constrained by internal biases arising from development and pre-existing design. We have attempted to quantify these biases by measuring eight life history characters in developmental mutants of Volvox carteri. Most of the mutants in our sample were inferior to the wild type, but deviated by less than tenfold from the wild-type mean. Characters differed in mutability, suggesting different levels of canalisation. Most correlations between life history characters among strains were positive, but there was a significant negative correlation between the size and the number of reproductive cells, suggesting an upper limit to the total quantity of germ produced by individuals. The most extreme phenotypes in our sample were very vigorous, showing that not all mutations of large effect are unconditionally deleterious. We investigated the effect of developmental constraints on the course of evolution by comparing the variance and covariance patterns among mutant strains with those among species in the family Volvocaceae. A close correspondence between patterns at these two levels would suggest that pre-existing design has a strong influence on evolution, while little or no correspondence shows the action of selection. The variance generated by mutation was equal to that generated by speciation in the family Volvocaceae, the genus Volvox, or the section Merillosphaera, depending on the character considered. We found that mutation changes the volume of somatic tissue independently of the quantity of germ tissue, so that the interspecific correlation between soma and germ can be attributed to selection. The negative correlation between size and number of germ cells among mutants of V. carteri is also seen among the larger members of the family (Volvox spp.), but not among the smaller members, suggesting a powerful design constraint that may be responsible for the absence of larger forms in the entire group.     

Internal rhythms in humans

Human physiology and behavior are characterized by a daily internal temporal dimension. This so-called circadian rhythmicity is present for almost all variables studied to date, persists in the absence of external cycles, and is synchronized to the external 24-h world by an internally generated circadian rhythm of light sensitivity. The light-sensitive circadian pacemaker, presumably also in humans located in the suprachiasmatic nucleus of the hypothalamus, drives the endogenous circadian component of rhythmicity for a number of variables including plasma melatonin, alertness, sleep propensity and sleep structure. Overt rhythmicity and the consolidation of vigilance states are generated by a fine-tuned interaction of this circadian process with other regulatory processes such as sleep homeostasis.     

Development of the jamming avoidance response and its morphological correlates in the gymnotiform electric fish,Eigenmannia

The electric fish, Eigenmannia, will smoothly shift the frequency of its electric organ discharge away from an interfering electric signal. This shift in frequency is called the jamming avoidance response (JAR). In this article, we analyze the behavioral development of the JAR and the anatomical development of structures critical for the performance of the JAR. The JAR first appears when juvenile Eigenmannia are approximately 1 month old, at a total length of 13–18 mm. We have found that the establishment of much of the sensory periphery and of central connections precedes the onset of the JAR. We describe three aspects of the behavioral development of the JAR: (a) the onset and development of the behavior is closely correlated with size, not age; (b) the magnitude (in Hz) of the JAR increases with size until the juveniles display values within the adult range (10–20 Hz) at a total length of 25–30 mm; and (3) the JAR does not require prior experience or exposure to electrical signals. Raised in total electrical isolation from the egg stage, animals tested at a total length of 25 mm performed a correct JAR when first exposed to the stimulus. We examine the development of anatomical areas important for the performance of the JAR: the peripheral electrosensory system (mechano- and electroreceptors and peripheral nerves); and central electrosensory pathways and nuclei [the electrosensory lateral line lobe (ELL), the lateral lemniscus, the torus semicircularis, and the pacemaker nucleus]. The first recognizable structures in the developing electrosensory system are the peripheral neurites of the anterior lateral line nerve. The afferent nerves are established by day 2, which is prior to the formation of receptors in the epidermis. Thus, the neurites wait for their targets. This sequence of events suggests that receptor formation may be induced by innervation of primordial cells within the epidermis. Mechanoreceptors are first formed between day 3 and 4, while electroreceptors are first formed on day 7. Electroreceptor multiplication is observed for the first time at an age of 25 days and correlates with the onset of the JAR. The somata of the anterior lateral line nerve ganglion project afferents out to peripheral electroreceptors and also send axons centrally into the ELL. The first electroreceptive axons invade the ELL by day 6, and presumably a rough somatotopic organization and segmentation within the ELL may arise as early as day 7. Axonal projections from the ELL to the torus develop after day 18. Within the torus semicircularis, giant cells are necessary for the performance of the JAR. Giant cell numbers increase exponentially during development and the onset of the JAR coincides with a minimum of at least 150 giant cells and the attainment of a total length of at least 15 mm and at least 150 giant cells. Pacemaker and relay cells comprise the adult Eigenmannia pacemaker nucleus. The growth and differentiation of these cell types also correlates with the onset of the JAR in developing animals. We describe a gradual improvement of sensory abilities, as opposed to an explosive onset of the mature JAR. We further suggest that this may be a rule common in most developing behavioral systems. © 1992 John Wiley & Sons, Inc.     

Hesperidin depolarizes the pacemaker potentials through 5-HT4 receptor in murine small intestinal interstitial cells of Cajal

ABSTRACT

Hesperidin, a citrus flavonoid, can exert numerous beneficial effects on human health. Interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal (GI) tract. In the present study, we investigated potential effects of hesperidin on pacemaker potential of ICC in murine small intestine and GI motility. A whole-cell patch-clamp configuration was used to record pacemaker potential in ICC, and GI motility was investigated in vivo by recording gastric emptying (GE) and intestinal transit rate (ITR). Hesperidin depolarized pacemaker potentials of ICC in a dose-dependent manner. Pre-treatment with methoctramine or 4-DAMP did not inhibit hesperidin-induced pacemaker potential depolarization. Neither a 5-HT₃ receptor antagonist (Y25130) nor a 5-HT₇ receptor antagonist (SB269970) reduced the effect of hesperidin on ICC pacemaker potential, whereas the 5-HT₄ receptor antagonist RS39604 was found to inhibit this effect. In the presence of GDP–β–S, hesperidin-induced pacemaker potential depolarization was inhibited. Moreover, in the presence of U73122 and calphostin C, hesperidin did not depolarize pacemaker potentials. Furthermore, hesperidin accelerated GE and ITR in vivo. These results imply that hesperidin depolarized ICC pacemaker potential via 5-HT₄ receptors, G protein, and PLC/PKC dependent pathways and that it increased GI motility. Therefore, hesperidin may be a promising novel drug to regulate GI motility.     

Conventional single-chamber pacemakers versus transcatheter pacing systems in a “real world” cohort of patients: A comparative prospective single-center study

PurposeDespite the developments in conventional transvenous pacemakers (VVI-PM), the procedure is still associated with significant complications. Although there are no prospective clinical trials that compared VVI-PM with transcatheter pacemaker systems (TPS).MethodsThis is a prospective, observational, single-center study that included all patients with an indication for a single-chamber pacemaker implant within a 4-year period. All clinical, ECG and echocardiographic characteristics at implant, electrical parameters, associated complications and mortality were analyzed. A Cox survival model and a Bayesian cohort analysis were performed for differences in complication rates between groups.ResultsThere were 443 patients included (198 TPS and 245 VVI-PM). The mean age was 81.5 years (TPS group, 79.2 ± 6.6 years; VVI-PM group, 83.5 ± 8.9 years). There was a male predominance in TPS group (123, 62.1% vs. 67, 27.3%; p < 0.001). The presence of systolic dysfunction and renal insufficiency were more frequent in VVI-PM group than in TPS patients. Mean follow-up was 22.3 ± 15.9 months. In a multivariable paired data the TPS group presented fewer complications than VVI-PM group (HR = 0.39 [0.15–0.98], p-value 0.013), but major complications were not different (6, 3% vs 14, 5.6% respectively, p = 0.1761). There was no difference in the mortality rate between the groups. The TPS group had less risk than VVI-PM group to have a complication, with a 96% of probability.ConclusionsTPS patients had a lower overall complication rate than VVI-PM patients including matched-pair samples using a Bayesian analysis. These results confirm the safety profile of TPS in clinical practice.