Central clocking.

The main questions in circadian neurobiology are: how many oscillators are involved; how are their daily oscillations generated and synchronized to the external world; and how do they signal time of day to the organism. The suprachiasmatic nuclei of the hypothalamus (SCN) are well established as the principal circadian oscillator of mammals. Their 10,000 or so 'clock' neurones drive our overt rhythms-the daily patterning we observe in our physiology and behaviour being mirrored perfectly by their spontaneous cycle of neuronal activity.

Expression of the thyroid hormone receptor gene, erbAalpha, in B lymphocytes: alternative mRNA processing is independent of differentiation but correlates with antisense RNA levels.

The erbAalpha gene encodes two alpha-thyroid hormone receptor isoforms, TRalpha1 and TRalpha2, which arise from alternatively processed mRNAs, erbAalpha1 (alpha1) and erb alpha2 (alpha2). The splicing and alternative polyadenylation patterns of these mRNAs resemble that of mRNAs encoding different forms of immunoglobulin heavy chains, which are regulated at the level of alternative processing during B cell differentiation. This study examines the levels of erbAalpha mRNA in eight B cell lines representing four stages of differentiation in order to determine whether regulation of the alternatively processed alpha1 and alpha2 mRNAs parallels the processing of immunoglobulin heavy chain mRNAs.

A thalamic contribution to arousal-induced, non-photic entrainment of the circadian clock of the Syrian hamster.

It is well established that the circadian clock of the suprachiasmatic nuclei (SCN) is entrained by light. More recently, the potent effects of arousing, non-photic cues on the clock have been recognized. The neural mediators of non-photic entrainment are yet to be identified.

Melatonin-sensitive, serum-stimulated signalling in ovine pars tuberalis.

In primary cultures of ovine pars tuberalis (oPT), serum acts through melatonin-sensitive mechanisms independent of cyclic AMP to increase the phosphorylation of the Ca2+/cyclic AMP response element binding protein (CREB). Immunocytochemical and biochemical assays were used to characterize the active components of serum and the signalling pathways through which they and melatonin function in oPT. The stimulatory effect of serum was heat-labile, sensitive to precipitation by methanol, and required components with a mass greater than 10 KDa implicating peptide or protein factors as the active agent.

A role for the circadian clock of the suprachiasmatic nuclei in the interpretation of serial melatonin signals in the Syrian hamster.

Seasonal rhythms of reproduction in the Syrian hamster are triggered by the pineal hormone melatonin. By varying the parameters of systemic infusions of exogenous melatonin delivered to pinealectomized hamsters, it has been shown that the hypothalamus is sensitive to the duration of individual signals, which serve as an inverse coding of day length. It also has been shown that animals are sensitive to the temporal structure of a series of signals insofar as a series of melatonin infusions of appropriate number and duration may fail to invoke a gonadal response if they are presented at inappropriate frequencies.

Are nuclear receptors involved in pituitary responsiveness to melatonin?

Evidence suggests that the pineal hormone melatonin modulates prolactin (PRL) secretion in part through direct effects on the anterior pituitary. However, high-affinity membrane receptors for melatonin are only found in the pars tuberalis (PT) of the anterior pituitary, whereas lactotrophs are confined to the pars distalis (PD). This study therefore sought to determine whether melatonin might have direct effects on the PD, through alternate pathways.

Phosphorylation of CREB in ovine pars tuberalis is regulated both by cyclic AMP-dependent and cyclic AMP-independent mechanisms.

This study used a combination of Western blotting and immunocytochemistry to test whether signalling pathways independent of cyclic AMP have the potential to induce phospho-CREB (pCREB)-like immunoreactivity (-ir) in the oPT. Western blot analysis of extracts of primary cultures of oPT using an antiserum against CREB, revealed a major band of CREB-ir at 44 KDa. The intensity of this band did not vary systematically with treatment.

Production of a prolactin releasing factor by the ovine pars tuberalis.

The anterior pituitary hormone prolactin is involved in the regulation of a wide variety of processes including mammary growth, lactation, reproduction and pelage growth (1). Correspondingly, in seasonal breeders, pronounced photoperiod-driven, seasonal changes occur in the levels of prolactin secretion (2). These effects are thought to be mediated by the pineal hormone melatonin, which acts as a humoral indicator of photoperiod (3).

The tau mutation in the Syrian hamster alters the photoperiodic responsiveness of the gonadal axis to melatonin signal frequency.

This study investigated the role of the circadian timing system (CTS) in photoperiodic time measurement by examining the response of the tau mutant hamster to programmed infusions of melatonin. The mutation is a single Mendelian gene defect which accelerates circadian period from 24 h in the wild-type (WT) to 20 h in the homozygote. If the CTS does not contribute to the photoperiodic interpretation of the melatonin signal, then the tau mutation would not influence photoperiodic responses of pinealectomised (PX) animals to systemic infusions of melatonin (10 h) once every 20, 24 or 25 h, mimics short-daylengths and causes gonadal involution.

Effects of low-frequency underwater sound on hair cells of the inner ear and lateral line of the teleost fish Astronotus ocellatus.

Fish (Astronotus ocellatus, the oscar) were subject to pure tones in order to determine the effects of sound at levels typical of man-made sources on the sensory epithelia of the ear and the lateral line. Sounds varied in frequency (60 or 300 Hz), duty cycle (20% or continuous), and intensity (100, 140, or 180 dB re: 1 muPa). Fish were allowed to survive for 1 or 4 days posttreatment.

Serotonergic antagonists impair arousal-induced phase shifts of the circadian system of the syrian hamster.

Single episodes of arousal of Syrian hamsters 2 h before projected activity onset (i.e., CT 10) phase-advanced their free-running circadian rhythm of wheel-running.

Lesions of the melatonin- and androgen-responsive tissue of the dorsomedial nucleus of the hypothalamus block the gonadal response of male Syrian hamsters to programmed infusions of melatonin.

The objective of this study was to characterize a site at which it is likely that melatonin mediates photoperiodic control of reproduction in the male Syrian hamster. The first experiment was a comparison of the distributions of iodomelatonin (IMEL)-binding sites and cells immunoreactive to androgen receptors (AR-ir) in the medio-basal hypothalamus (MBH). AR-ir cells extended throughout the MBH, whereas IMEL binding was restricted to the dorsomedial nucleus (DMN).

FosB in the suprachiasmatic nucleus of the Syrian and Siberian hamster.

The suprachiasmatic nucleus (SCN) generates circadian rhythms of behavior and hormone secretion in mammals, and integrates responses to light and nonphotic stimuli to synchronize such rhythms with the external environment. Previous studies have demonstrated a close association between the induction of the immediate early gene (IEG) c-fos in the SCN by light and phase shifts of circadian rhythms induced by light, but nonphotic stimuli (e.g.

Modeling and measuring lateral line excitation patterns to changing dipole source locations.

In order to determine excitation patterns to the lateral line system from a nearby 50 Hz oscillating sphere, dipole flow field equations were used to model the spatial distribution of pressures along a linear array of lateral line canal pores. Modeled predictions were then compared to pressure distributions measured for the same dipole source with a miniature hydrophone placed in a small test tank used for neurophysiological experiments. Finally, neural responses from posterior lateral line nerve fibers in the goldfish were measured in the test tank to demonstrate that modeled and measured pressure gradient patterns were encoded by the lateral line periphery.

Regulation of mitogen-activated protein kinase in the pars tuberalis of the ovine pituitary: interactions between melatonin, insulin-like growth factor-1, and forskolin.

The pars tuberalis (PT) of the anterior pituitary is notable for the expression of levels of melatonin receptors that consistently exceed those in all other tissues in mammals. For this reason and because of its anatomical position, it has been suggested that the PT may play a role in seasonal reproductive responsiveness. However, no data have been forthcoming on the nature of the melatonin-responsive cells in this tissue or on the interaction of melatonin with other hormonal signals in the control of PT cells.

Melatonin receptors in the rat brain and pituitary.

2-(125I)iodomelatonin binding has been mapped and characterized in the brain and pituitary of the male laboratory rat using quantitative in vitro autoradiography. Specific binding was defined as that completely displaced in the presence of 1 microM melatonin. In the brain high levels of binding were localized over the suprachiasmatic nucleus (SCN), the area postrema (AP), and the spinal tract of the trigeminal nerve (Sp5).

Gating of retinal inputs through the suprachiasmatic nucleus: role of excitatory neurotransmission.

The mammalian circadian clock, located in the hypothalamic suprachiasmatic nucleus (SCN) is important in the regulation of many circadian rhythms, including regulation of pineal gland metabolism and melatonin secretion. Transsection of the optic nerves, disrupting the retinohypothalamic pathway, lesion of the SCN, or lesion of the hypothalamic paraventricular nucleus (PVN) abolish the regulation of pineal serotonin N-acetyltransferase activity by light. Therefore, the pathways linking the retina and the pineal gland must be channelled from the retina through the SCN and the PVN.

Gonadal responses of the male tau mutant Syrian hamster to short-day-like programmed infusions of melatonin.

Changes in the duration of the nocturnal peak of the circadian rhythm of melatonin secretion by the pineal gland mediate pohotoperiodic control of reproductive cycles in mammals. The present study examined whether the tau mutation of the circadian clock of the Syrian hamster altered the ability of the animals to exhibit photoperiodic, gonadal responses to timed infusions of exogenous melatonin. Pinealectomized tau mutant and wild-type hamsters received s.

Effects of N-methyl-D-aspartate (NMDA) on seasonal cycles of reproduction, body weight and pelage colour in the male Siberian hamster.

Siberian hamsters (Phodopus sungorus) transferred from stimulatory photoperiods (long days: LD) to inhibitory photoperiods (short days: SD) undergo testicular regression within 8 weeks. This reproductive response to photoperiod was blocked by systemic daily treatment with the glutamatergic agonist N-methyl-D-aspartate (NMDA: 20 mg/kg BW, sc). This powerful effect of NMDA demonstrates the potential for endogenous glutamate to regulate reproductive function.

The inhibitory action of melatonin in the ovine pars tuberalis is not dependent on changes in plasma membrane potential.

Treatment of ovine pars tuberalis (oPT) cultures with forskolin activates adenylyl cyclase, leading to increased levels of cyclic AMP, activation of protein kinase A, phosphorylation of the calcium/cyclic AMP response-element binding protein and the increased synthesis and secretion of several proteins. Simultaneous treatment with melatonin inhibits or reverses these effects of forskolin. In the neonatal rat pituitary, the inhibitory effects of melatonin are mediated by changes in membrane potential.