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D K Welsh

Publications and source records attributed to D K Welsh.

12 recordsLinked to original sources
PubMed2001

A sleep diary and questionnaire study of naturally short sleepers.

Whereas most people require more than 6 h of sleep to feel well rested, there appears to be a group of people who can function well on between 3 and 6 h of sleep. The aims of the present study were to compare 12 naturally short (3-6 h) sleepers (9 males 3 females, mean age 39.6 years, SD age 10.1 years) recruited by a media publicity campaign with age, gender and chronotype matched medium length (7-8.5 h) sleepers on various measures. Measurement instruments included diaries and questionnaires to assess sleep duration and timing, as well as questionnaire assessments of sleep pathology, morningness-eveningness, extroversion, neuroticism, pathological daytime sleepiness, subclinical hypomania, optimism, depressive symptoms, exercise, and work habits. Few measures showed reliable differences between naturally short sleepers and controls except the obvious ones related to sleep duration. There was, however, some evidence for subclinical hypomanic symptoms in naturally short sleepers.

Adult↗
PubMed1996

Gap junctions couple astrocytes but not neurons in dissociated cultures of rat suprachiasmatic nucleus.

Individual neurons dissociated from rat suprachiasmatic nucleus can express independently phased circadian firing rhythms in culture. The phases of these rhythms are unperturbed by reversible blockade of neuronal firing lasting 2.5 days, indicating that multiple circadian clocks continue to operate in the absence of conventional synaptic transmission. The possibility remains, however, that these circadian rhythms might depend on some other form of intercellular communication. In the present study, a potential role for gap junctional coupling in SCN cultures was evaluated by introduction of the tracer molecule Neurobiotin into both neurons (n = 98) and astrocytes (n = 10), as well as by immunolabeling for specific connexins, the molecular components of gap junctions. Astrocytes were extensively coupled to each other by connexin 43-positive gap junctions, but no evidence was found for coupling of neurons to each other or to astrocytes. These data support the hypothesis that neurons expressing independently phased circadian rhythms in SCN cultures ('clock cells') are autonomous, single cell circadian oscillators, but do not exclude a role for glia in synchronizing neuronal clock cells in vivo.

Animals↗
PubMed1995

Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms.

Within the mammalian hypothalamus, the suprachiasmatic nucleus (SCN) contains a circadian clock for timing of diverse neuronal, endocrine, and behavioral rhythms. By culturing cells from neonatal rat SCN on fixed microelectrode arrays, we have been able to record spontaneous action potentials from individual SCN neurons for days or weeks, revealing prominent circadian rhythms in firing rate. Despite abundant functional synapses, circadian rhythms expressed by neurons in the same culture are not synchronized. After reversible blockade of neuronal firing lasting 2.5 days, circadian firing rhythms re-emerge with unaltered phases. These data suggest that the SCN contains a large population of autonomous, single-cell circadian oscillators, and that synapses formed in vitro are neither necessary for operation of these oscillators nor sufficient for synchronizing them.

Action Potentials↗
PubMed1990

Lithium lengthens circadian period in a diurnal primate, Saimiri sciureus.

Lithium lengthens the period of free-running circadian rhythms in a variety of species, but this effect has not been demonstrated unequivocally in primates. Because of the possible link between lithium's action on the circadian clock and its therapeutic action in human mood disorders, we tested the ability of lithium to lengthen circadian period in a diurnal primate with circadian properties similar to those of humans. Lithium carbonate was administered in food pellets to 8 adult male squirrel monkeys (Saimiri sciureus) for at least 27 consecutive days. Serum lithium levels on the last day of lithium administration ranged from 0.76 to 2.02 mEq/liter, comparable to the therapeutic range for treatment of bipolar disorder in humans (0.6-1.2 mEq/liter). Circadian periods of perch-hopping activity were longer during lithium treatment than during baseline in 7 of the 8 monkeys (changes of -0.08 to +1.41 hr, mean +0.55 hr, p = 0.01), and returned toward baseline values when lithium was discontinued. In most cases, the period change was evident within a few days after beginning full lithium dose, and was not accompanied by changes in level or pattern of activity, nor in amplitude of the circadian rhythm. Food consumption and body weight were reduced during lithium treatment, and rebounded on return to lithium-free diet. Period change was related to lithium dose (p less than 0.05), but did not correlate with food consumption, body weight, or baseline circadian period. These results, by establishing that lithium lengthens circadian period in primates, suggest that studying the cellular mechanisms of this circadian effect may be relevant to understanding lithium's therapeutic effect on mood in humans.

Animals↗
PubMed1990

Aluminum fluoride reveals a phosphoinositide system within the suprachiasmatic region of rat hypothalamus.

The phosphoinositide (PI) transduction system has proven to be of major importance in several regions of mammalian brain. In this report, we examined in rats whether a PI system is present in the hypothalamic suprachiasmatic nuclei (SCN), the site of a biological clock that generate circadian rhythms. Autoradiographic localization of phorbol ester binding revealed moderate levels of protein kinase C, a component of the PI system, in the SCN. Hypothalamic explants containing SCN showed substantial incorporation of [3H]myoinositol into lipids. AlF4-, a non-specific activator of G proteins, produced a dose-dependent increase in inositol monophosphate (IP1) levels in the explants in calcium-free medium, with a maximum increase of 216% of control at 50 mM NaF. Medium containing 1.8 mM calcium stimulated a similar increase in IP1 levels, but the stimulatory effects of AlF4- and calcium were not additive, so that the effect of Al4- was obscured in medium containing calcium. AlF4- stimulated accumulation of IP1, as well as inositol bis-, and trisphosphate, over a 40-min time course in the presence and absence of lithium (10 mM LiCl). Lithium, a known inhibitor of phosphatases in the inositol phosphate recycling pathway, raised levels of all 3 inositol phosphates in SCN explants both at baseline (without A1F4-) and after 30 min AlF4- stimulation. The results show the existence of a lithium-sensitive PI system within the suprachiasmatic region of the rat hypothalamus.

Aluminum↗
PubMed1986

Precision of circadian wake and activity onset timing in the mouse.

In each circadian cycle, a mouse begins its major activity period with discrete wake onset and activity onset events. The precision with which these events are timed in constant darkness was analyzed using the approach outlined by Pittendrigh and Daan (1976). Negative serial correlations of observed circadian period values (mean r1 = -0.471 for wake data, -0.409 for activity data) imply that deviations in period tend to be compensated by opposite deviations in the following cycle. As a result, precision of the circadian pacemaker must be better than that of observed rhythms. Standard deviation of the pacemaker period sigma(tau) was estimated at 5.1 min. Some individual data series had estimates s(tau) = 0, implying a nearly perfect pacemaker. Previous speculation was that wake onset would be under more direct pacemaker control than activity onset, and would therefore be timed more precisely (Pittendrigh and Daan 1976; Richardson et al. 1985). Contrary to this prediction, intervals between successive wake onsets exhibited significantly greater variance than intervals between successive activity onsets. Two possible interpretations of this finding were proposed.

Animals↗
PubMed1986

Effect of age on the circadian pattern of sleep and wakefulness in the mouse.

In elderly humans, daytime naps are common, nocturnal sleep is poorly consolidated, and the sleep period often begins and ends earlier than in young adults. Because previous work has suggested that rodents may provide a useful animal model for these changes, we conducted a detailed investigation of sleep patterns in 11 young adult and 9 old mice. Mice were surgically implanted for chronic EEG recording, and sleep state was monitored over multiple circadian cycles. During the active phase, old mice spent more time asleep and had shorter wake episodes compared with young mice. During the rest phase, old mice spent more time awake than young mice, and tended to have shorter episodes of sleep. No evidence was found, however, for earlier timing of sleep in older mice. These results suggest that the mouse may provide a suitable animal model for further study of certain age-related changes in temporal distribution of sleep and wakefulness.

Aging↗
PubMed1985

A circadian rhythm of hippocampal theta activity in the mouse.

Hippocampal theta activity dominates the cortical EEG of the mouse during certain behaviors. We have therefore been able to study the circadian distribution of hippocampal theta activity by means of chronic EEG implantation and computerized EEG state scoring. Observations in six mice indicate consistent and significant circadian patterns of theta-dominated EEG, both during wakefulness (theta-dominated wake, or TDW) and during sleep (REM sleep). The probability of REM rises gradually to a maximum during the sleep period and then falls abruptly at activity onset and then falls gradually. The complementary circadian patterns of REM and TDW suggest that they may be two episodes of each coincide remarkably, as do their circadian distributions. The probability of TDW rises to a very high level at activity onset and then falls gradually. The complementary circadian patterns of REM and TDW suggest that they may be two halves of a single circadian rhythm of theta probability. This concept would be relevant in interpreting the abnormally phase-advanced pattern of REM sleep observed in human depressives.

Animals↗