Biomedical subjects

G E Pickard

Publications and source records attributed to G E Pickard.

At least 37 records · Page 2Linked to original sources

PubMed1995

Restoration of circadian behavior by anterior hypothalamic heterografts.

The suprachiasmatic nucleus (SCN) of the anterior hypothalamus (AH) is a circadian oscillator and an important component of the mammalian circadian system. To determine whether the SCN is the dominant circadian pacemaker responsible for generating a species-typical characteristic of circadian rhythms [i.e., period length (tau)], neural transplantation was conducted using fetal AH donors of different species and SCN-lesioned (SCNx) hosts. The circadian behavior of each of the three donor species is clearly distinguishable by its species-typical tau. The extent of SCN pacemaker autonomy was assessed by noting whether the period of the restored circadian rhythm following heterograft transplantation was characteristic of the donor or the host, or whether an atypical circadian period was established. Hamsters rendered arhythmic by SCN ablation were implanted with AH tissue from fetal hamsters (E13-E14, homograft controls) or fetal mice or rats (E15-E17). The AH homografts restored circadian activity rhythms with a tau similar to that of intact hamsters, and fetal mouse AH heterografts restored circadian rhythmicity with a tau similar to that of the donor mouse strain. However, fetal rat AH tissue implanted into SCNx hamsters renewed circadian rhythmicity with a period significantly shorter than either the species-typical tau of the rat donor or the hamster host. In both the mouse and rat AH heterograft experiments, immunocytochemical analysis performed with species-specific monoclonal antibodies revealed extensive fiber outgrowth from the implant into the host hypothalamus, evident up to 7 months postimplantation. The rat implants were consistently larger, more fully vascularized and exhibited less necrosis than the implanted mouse tissue. The histological appearance of the grafts, thus, provides no explantation for the difference in efficacy of the grafts to restore species-typical behavior. However, several interpretations are considered that are consistent with the combined behavioral results observed.

Animals↗

PubMed1994

Intergeniculate leaflet ablation alters circadian rhythms in the mouse.

The intergeniculate leaflet (IGL) receives retinal input and sends afferents to the hypothalamic suprachiasmatic nucleus (SCN), a circadian oscillator. The effect of IGL ablation on the circadian rhythm of wheel-running activity was examined in mice maintained in constant dark (DD) and in two intensities of constant light (LL). IGL-lesioned animals demonstrated significantly longer free-running rhythms in DD conditions than IGL-intact mice similarly housed; there was no effect of IGL ablation on the period of the free-running activity rhythm in LL of either 10 or 100 lux intensity. A change in the period of the free-running activity rhythm in DD following IGL destruction is evidence that the IGL exerts an endogenous influence on the SCN circadian system.

Animals↗

PubMed1994

Pineal photoreceptors rhythmically secrete melatonin.

Individual pineal cells secrete melatonin with a circadian period, reducing a vertebrate circadian system to the level of a single cell [Brain Res., 627 (1993) 141-146]. In the present study, dissociated pineal cells were identified as melatonin-secreting by a reverse hemolytic plaque assay (RHPA) and all melatonin-secreting cells were immuno-positive when analyzed for the photoreceptor protein S-antigen. The results are the first direct evidence that isolated photoreceptor cells secrete melatonin and taken together with our previous findings indicate that single pineal cells contain: (1) a circadian oscillator; (2) a photoreceptive capacity; and (3) the ability to secrete melatonin rhythmically.

Animals↗

PubMed1994

Retinohypothalamic projections and immunocytochemical analysis of the suprachiasmatic region of the desert iguana Dipsosaurus dorsalis.

Two separate and distinct retinal projections to the hypothalamus in the iguanid lizard Dipsosaurus dorsalis were described using horseradish peroxidase and cobalt-filling techniques. Both of the projections were unilateral and completely crossed; one terminated in the supraoptic nucleus and the other in the suprachiasmatic nucleus. Immunocytochemical analysis showed that the supraoptic nucleus contained cell bodies and fibers that cross-react with antibodies raised against arginine vasopressin, while the suprachiasmatic nucleus contained arginine vasopressin-like immunoreactive fibers emanating from cells in the nearby paraventricular nucleus. The suprachiasmatic nucleus contained a dense plexus of fibers that cross-reacted with neuropeptide-Y antibody. Antiserum against vasoactive intestinal polypeptide showed no reactivity in any part of the forebrain, while antiserum against serotonin showed sparse and uniform reactivity throughout the forebrain, including the suprachiasmatic nucleus. These results, together with other data, indicate that the suprachiasmatic nucleus of D. dorsalis is homologous to the suprachiasmatic nuclei of rodents, structures known to contain circadian pacemakers. We suggest that the suprachiasmatic nucleus may play a similar role in the circadian system of D. dorsalis.

Afferent Pathways↗

PubMed1993

Individual pineal cells exhibit a circadian rhythm in melatonin secretion.

Pineal glands and dissociated pineal cells exhibit a circadian rhythm of melatonin secretion in vitro which persists for several cycles under constant conditions. It is not known whether individual, physically isolated pineal cells are capable of generating a circadian oscillation in melatonin release. This question was addressed by utilizing a reverse hemolytic plaque assay for the detection of melatonin secretion from individual pineal cells. Dissociated pineal cells from the anole lizard, maintained in short term culture, displayed a marked variation in melatonin secretion for up to 72 h under both cyclic lighting conditions and in constant dark. The persistence of daily fluctuations of melatonin secretion from individual cells strongly suggests that individual pineal cells can function as circadian oscillators.

Animals↗

PubMed1993

Time course of fiber outgrowth from fetal anterior hypothalamic heterografts.

Fetal anterior hypothalamic (AH) heterografts can restore circadian rhythmicity to animals rendered arrhythmic following ablation of the suprachiasmatic nucleus (SCN). Behavioral restoration of circadian activity typically begins between two and six weeks post-implantation. The time course of fiber outgrowth from fetal AH heterografts was examined to determine whether neuronal outgrowth from the implants precedes the typically observed effects of such implants upon circadian behavior. Fetal mouse or rat AH tissue containing the SCN was implanted into the third ventricle of SCN-lesioned hamsters. Using species-specific monoclonal antibodies generated against mouse or rat neuronal elements, fiber outgrowth into the host hypothalamus was examined at 2, 4, 7, 14, 30 and 45 days after implantation. Fibers were observed to have emerged from the implant at the earliest time point examined. Four days after surgery, individual fibers had extended up to 0.6 mm into the host neuropil. By 14 days post-implantation, outgrowth from the implant had formed a dense fiber plexus in the host hypothalamus. This observation demonstrates that neuronal integration of the implant with the host brain begins within 48 hours of implantation, and is extensively established well before a restoration of rhythmicity is typically observed. Thus, on the basis of the time course of fiber outgrowth, it is clear that neuronal contact between graft and host may mediate the observed restoration of circadian rhythmicity.

Animals↗

PubMed1993

Light intensity and splitting in the golden hamster.

Hamster circadian activity rhythms split into two components during prolonged exposure to conditions of constant light (LL). Several aspects of this phenomenon were examined in this study. The frequency of splitting was significantly greater among animals exposed to LL of 100 lux intensity (LL100) compared with animals in LL10. Animals that split had significantly longer free-running periods (tau) compared to nonsplitters and the decrease in tau associated with splitting was highly correlated with the presplit tau. Splitting was also observed under continuous dim light which fluctuated rhythmically from 5-10 lux. Thus, splitting of the circadian rhythm of activity is positively correlated with LL intensity with an LL intensity threshold for the induction of splitting in the range of 3-5 lux.

Animals↗

PubMed1990

Circadian locomotor rhythms in the desert iguana. II. Effects of electrolytic lesions to the hypothalamus.

Desert iguanas, Dipsosaurus dorsalis, displaying freerunning circadian locomotor rhythms in conditions of constant darkness and temperature received electrolytic lesions to the hypothalamus. The locomotor activity of those lizards (N = 9) which sustained 80% or more damage to the suprachiasmatic nucleus (SCN) became arrhythmic whereas all animals that sustained less than 35% damage to the SCN remained rhythmic, even though they sustained significant damage to nearby regions of the hypothalamus and preoptic area. These results suggest strongly that the SCN plays a role in the regulation of circadian rhythms in the desert iguana. Taken together with other evidence, they support the view that this structure is homologous to the mammalian SCN, which acts as a pacemaker in the circadian system.

Animals↗

PubMed1989

Entrainment of the circadian rhythm of wheel-running activity is phase shifted by ablation of the intergeniculate leaflet.

The phase angle of entrainment of golden hamster wheel-running activity was determined before and after bilateral destruction of the intergeniculate leaflet (IGL). Animals were maintained under continuous dim light which rhythmically varied in intensity (10-5 lux) in the form of a sine wave with a 24 h period. The phase angle of entrainment changed significantly following IGL ablation suggesting a role for the IGL in entrainment.

Animals↗

PubMed1987

Circadian rhythm of nociception in the golden hamster.

The response latency of golden hamsters to nociceptive stimuli was measured under cyclic lighting conditions and during constant illumination. A day-night rhythm of nociception was demonstrated; response latencies were significantly longer during the day. A circadian rhythm of nociception was displayed by hamsters maintained for 30 days in constant dim light. Short response latencies noted under these conditions were associated with the inactive period of the animals circadian cycle (subjective day). The experiments provide data which indicate the phase relationship between the circadian rhythms of nociception and locomotor activity differs under entrained and free-running conditions.

Animals↗

PubMed1987

The intergeniculate leaflet partially mediates effects of light on circadian rhythms.

Photic signals affect circadian activity rhythms by both phasic and tonic mechanisms that modulate pacemaker phase and period. In mammals, the effects of light on circadian activity are mediated by the retina, which communicates with the suprahiasmatic nucleus (SCN) by two different anatomical routes: the retino-hypothalamic tract (RHT), originating in the retina, and the geniculo-hypothalamic tract (GHT), arising from a retino-recipient nucleus, the intergeniculate leaflet (IGL). We assessed the roles of these two afferent systems in mediating phasic and tonic effects of light on circadian activity in IGL-lesioned animals. Destruction of the IGL significantly affected phase shifts produced by brief light pulses (phasic effect) and modified the change in period (tau) of the free-running activity rhythm produced by changing the level of constant light (LL) (tonic effect). Phase advances produced by brief light pulses were decreased in amplitude while phase delays were increased in IGL-lesioned animals as compared to controls. The free-running period in constant dark (tau DD) of IGL-lesioned animals was greater than tau DD of controls, and the lengthening of tau normally produced by LL was not observed or was greatly reduced in IGL-lesioned animals. Entrainment to light-dark cycles was unaffected by the lesions, as were other aspects of the circadian activity rhythm that normally change in response to LL (e.g., activity-rest ratio, total activity, splitting). Our data support the interpretation that the IGL plays a significant role in relaying information regarding illumination intensity to the SCN.

Animals↗

PubMed1986

Influence of deuterium oxide on circadian activity rhythms of hamsters: role of the suprachiasmatic nuclei.

The period of the free-running circadian activity rhythm of Syrian hamsters was measured before and during treatment with 10% deuterium oxide (D2O). Deuteration increased period length by approximately 0.5 h per cycle both pre- and postoperatively in hamsters sustaining complete, incomplete or no unilateral lesions of the suprachiasmatic nuclei (SCN). Neither coupling between the bilaterally paired SCN, nor elimination of 50% of SCN tissue affected period length during D2O treatment. However, variability of the response to D2O was much greater in lesioned than in intact hamsters. We propose that a small percentage of the normal complement of SCN neurons is sufficient to permit full responsiveness of the circadian system to D2O and that there is substantial redundancy in the neural system that responds to deuterium. Stability of the circadian system appears to be increased by the full complement of SCN neurons.

Animals↗

PubMed1985

Persistence of circannual rhythms in ground squirrels with lesions of the suprachiasmatic nuclei.

Golden-mantled ground squirrels (Spermophilus lateralis) sustained complete ablation of the suprachiasmatic nuclei (SCN) while being maintained under constant conditions of photoperiod, temperature and food availability. After SCN ablation, most squirrels observed for up to 3 years postsurgically underwent normal circannual cycles in body mass. Other squirrels with similar SCN damage evidenced various anomalies in their circannual body weight cycles. Response of squirrels to SCN ablation was not related to the phase of the annual cycle in which lesions were produced. The variable nature of the effect of SCN ablation on circannual body mass cycles suggests that the SCN are non-essential components of the system underlying the generation or expression of circannual rhythms.

Animals↗

PubMed1985

Bifurcating axons of retinal ganglion cells terminate in the hypothalamic suprachiasmatic nucleus and the intergeniculate leaflet of the thalamus.

At least some retinal axons afferent to the hypothalamic suprachiasmatic nucleus (SCN; a circadian oscillator) bifurcate in the optic chiasm (O.E. Millhouse, Brain Res., 137 (1977) 351-355). The termination site(s) of the axonal branch that continues in the optic tract is unknown. Injection of the fluorescent tracer, True Blue, into the SCN and the fluorescent dye, Nuclear Yellow, into the lateral geniculate complex resulted in the labeling of individual retinal ganglion cells with both tracers. However, only Nuclear Yellow injections which included the intergeniculate leaflet (IGL) resulted in double-labeled ganglion cells in the retinae. These results indicate that individual retinal ganglion cells innervate both the hypothalamic SCN and the IGL of the thalamus by means of divergent axonal collaterals. Moreover, neurons of the IGL are afferent to the SCN, thereby forming a complex circuit within which photic information from the same retinal ganglion cell may influence the SCN both directly and after thalamic processing.

Animals↗

PubMed1984

Immunohistochemical localization of luteinizing hormone-releasing hormone (LHRH) in the hypothalamus of adult female hamsters treated neonatally with monosodium glutamate or hypertonic saline.

The immunohistochemical localization of luteinizing hormone-releasing hormone (LHRH) was studied in paraffin and vibratome-sectioned tissue from adult female hamsters that were treated neonatally with monosodium glutamate (MSG) or hypertonic saline. There appeared to be a reduction in LHRH-positive fibers in the median eminence of animals with an MSG-induced lesion of the arcuate nucleus in paraffin-embedded tissue. However, when unembedded tissue was cut on a vibratome, the distribution of LHRH-positive fibers and perikarya was similar in both groups of animals. Fibers were seen coursing through the periventricular area and lateral hypothalamus to the median eminence. In addition, LHRH-positive fibers were seen in the organum vasculosum of the lamina terminalis, subfornical organ, septal and preoptic areas, fasciculus retroflexus, habenular complex, and several regions in the basal forebrain. Animals that were pretreated with colchicine had LHRH-positive perikarya in the medial habenular nucleus, diagonal band of Broca, and the medial olfactory tract.

Animals↗

PubMed1984

Splitting of the circadian rhythm of body temperature in the golden hamster.

The circadian rhythm of hamster locomotor activity "splits" into two distinct circadian components during conditions of constant illumination. To determine if the circadian rhythm of body temperature also splits under these conditions, body temperature and locomotor activity were monitored concurrently in animals housed in constant illumination. Splitting of the body temperature rhythm into two circadian components was observed in animals manifesting split activity rhythms. Concurrent splitting of both rhythms suggests a common mechanism either for the generation or coupling of these rhythms.

Animals↗

PubMed1983

The hypothalamic paraventricular nucleus mediates the photoperiodic control of reproduction but not the effects of light on the circadian rhythm of activity.

Photoperiods of less than 12.5 h of light/24 h induce gonadal regression in the golden hamster. Photic information is relayed from the retina to the hypothalamic suprachiasmatic nucleus (SCN), a structure responsible for the generation of many circadian rhythms including the circadian rhythms in locomotor activity and pineal melatonin synthesis and release. Although pineal melatonin mediates the photoperiodic-neuroendocrine response, the complete neural circuit from the SCN to the pineal gland is unknown. Complete destruction of the hypothalamic paraventricular nucleus (PVN) prevented short-day-induced testicular regression without affecting the circadian rhythm of locomotor activity. The results indicate that the PVN plays an important role in the photoperiodic-neuroendocrine circuit and is responsible for relaying information from the SCN to the pineal. A different efferent pathway connects the SCN to structures in the brain responsible for locomotor activity.

Animals↗

PubMed1983

The suprachiasmatic nuclei: two circadian clocks?

Unilateral lesions of the bilaterally paired suprachiasmatic nuclei of the hypothalamus were made in golden hamsters maintained in constant light (LL). Prior to surgery, the circadian rhythm of locomotor activity had dissociated or 'split' into two distinct components in 19 out of 30 hamsters, while in the remaining 11 animals (i.e. non-splitters) a normal rhythm with a single bout of activity was maintained. Following destruction of a major portion (i.e. 50-100%) of a single suprachiasmatic nucleus (SCN) in 6 'split' and 5 'non-split' hamsters, a single circadian bout of activity was observed in all animals. In 9 of these 11 animals the circadian period of the activity rhythm was altered following unilateral SCN lesions. In two split animals sustaining lesions which missed the SCN, but disrupted efferents caudal to the SCN, the split condition was also abolished. Lesions which destroyed less than 50% of a single SCN did not abolish the split condition (n = 6) and had little effect on the circadian pattern of the non-splitters (n = 5). In contrast, bilateral destruction of the suprachiasmatic nuclei eliminated the circadian pattern of activity in both 'split' (n = 5) and 'non-split' (n = 1) animals. These results demonstrate that each SCN is capable by itself of maintaining circadian rhythmicity and that at least two circadian oscillators, or oscillating systems, reside within the suprachiasmatic nuclei.

Animals↗