Biomedical subjects

B Rusak

Publications and source records attributed to B Rusak.

At least 73 records · Page 4Linked to original sources

PubMed1990

Neurophysiological responses to melatonin in the SCN of short-day sensitive and refractory hamsters.

The pineal hormone melatonin plays a central role in the regulation of seasonal reproductive cycles in mammals and several studies have implicated the suprachiasmatic nucleus (SCN) as a target on which melatonin acts. The Syrian hamster is a long-day breeder which exhibits gonadal regression when housed in short (less than 12.5 h) daily photoperiods or injected daily with melatonin in long photoperiods. In the present paper we address the question whether melatonin affects firing rates of SCN neurones and whether these effects change as the animals become refractory to short photoperiods. In long-day (LD14:10) hamsters SCN neurones were suppressed (31%), activated (15%) or unaffected (54%) by melatonin. In contrast, there was an increased proportion of melatonin insensitive cells (88%) in short-day (refractory) hamsters. Melatonin-responsive cells were found primarily during the late projected day and early projected night in both long-day and short-day animals. This reduced responsiveness of SCN neurones to melatonin in hamsters refractory to short-day exposure may represent part of the mechanism underlying the development of gonadal refractoriness and the onset of gonadal growth in anticipation of long spring photoperiods.

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PubMed1990

Light pulses that shift rhythms induce gene expression in the suprachiasmatic nucleus.

Lighting cycles synchronize (entrain) mammalian circadian rhythms by altering activity of cells in the suprachiasmatic nucleus (SCN) of the hypothalamus, a circadian pacemaker. Exposure of hamsters and rats to light pulses at those phases of the circadian rhythm during which light can shift the rhythm caused increased immunoreactivity for the product of the immediate-early gene c-fos in cells in the region of the SCN that receives retinal fibers. Light pulses also increased messenger RNA for the Fos protein and for the immediate-early protein NGFI-A in the rat SCN. Similar increases in mRNA for NGFI-A were seen in the SCN of hamsters. Thus cells in this portion of the SCN undergo alterations in gene expression in response to retinal illumination, but only at times in the circadian cycle when light is capable of influencing entrainment.

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PubMed1990

Lesions dorsal to the suprachiasmatic nuclei abolish split activity rhythms of hamsters.

Constant light exposure (LL) can result in "splitting" of circadian rhythms into two components coupled about 12 hr apart. Splitting has been interpreted as evidence for the presence of two main oscillators or groups of oscillators underlying circadian rhythms. Abolition of splitting after unilateral suprachiasmatic nucleus ablation suggested that each suprachiasmatic nucleus could correspond to one of these component oscillators. We examined whether lesions outside the suprachiasmatic nuclei (SCN) would abolish split activity rhythms of hamsters in LL. Wheel-running activity was recorded for 3 months after surgery. Tissue damage was assessed by Klüver-Barrera staining. Damage to areas dorso-caudal to the SCN was able to abolish the split condition. Bilateral damage to the anterior SCN, partial unilateral SCN ablation or unilateral periventricular damage also abolished the split pattern. These results indicate that destruction of one SCN is not essential for the elimination of split rhythms since lesions dorsal to the SCN or partial bilateral SCN damage are also effective. Indirect lesion effects on SCN function or damage to extra-SCN oscillators may account for the loss of the split condition.

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PubMed1990

Neurotransmitters in the mammalian circadian system.

This discussion of the roles of transmitters in the circadian system has focused mostly on the entrainment mechanism because it is not clear to what extent neurotransmission is important to the other major function of circadian systems, rhythm generation. Schwartz et al (1987) have presented evidence that the circadian pacemaker in the SCN continues to run, but cannot be entrained by light, when tetrodotoxin is used to block sodium-dependent action potentials. Although other forms of intercellular communication are not ruled out, these results suggest that classical synaptic neurotransmission is important for entrainment but not for rhythm generation. That the SCN contains a cholinergic marker like ChAT and is responsive to cholinergic agents but does not bind nicotine or ACh reflects a general problem in reconciling functional, physiological, and anatomical markers of neurotransmission. A mismatch between the anatomical distributions of transmitters and their receptor-binding sites is a common observation, the meaning of which remains enigmatic (Herkenham 1987). Also, the neurophysiological consequences of injections of drugs into parts of the brain involved in rhythm regulation remain largely unknown. Interpretations of the effects of these treatments on rhythms are predicated on assumptions that may not be valid; e.g. that a bolus injection of an excitatory substance has its primary effect by activating neurons. Still to be established is whether the effects of drugs when they are administered in behavioral pharmacology studies reflect their effects on cellular functions and on neuronal responses to photic cues when they are delivered at near-physiological levels to single neurons.

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PubMed1989

Photic sensitivity of geniculate neurons that project to the suprachiasmatic nuclei or the contralateral geniculate.

We applied tests of antidromic activation to identify cells in the hamster intergeniculate leaflet (IGL) that project to either the suprachiasmatic nucleus (SCN) or the contralateral IGL. IGL cells projecting to these targets were tested for photic responses; most showed sustained activation, while a few were suppressed by retinal illumination. Stimulation of one IGL typically suppressed firing in contralateral IGL cells and inhibited responses to immediately succeeding photic stimulation.

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PubMed1989

Photically responsive neurons in the hypothalamus of a diurnal ground squirrel.

The suprachiasmatic nuclei (SCN) function as a circadian pacemaker. Entrainment to the external light-dark cycle is mediated by the retina which gives rise to both direct and indirect projections to the SCN. The hypothalamic targets of the retinohypothalamic tract (RHT) were investigated in thirteen-lined ground squirrels (Spermophilus tridecemlineatus) following WGA-HRP injections. The results indicate that retinal fibers project to the entire SCN. Extracellular single-unit activity was recorded in and near the SCN of thiopental sodium anesthetized squirrels while the eyes were photically stimulated. A small population of hypothalamic cells were responsive to retinal illumination. About half of these cells were activated by light while the others were light-suppressed. The majority of these cells responded in a sustained way to light pulses. Light intensities of at least 1000 lux appeared necessary to induce a sustained response to light. No differences in light responsiveness were observed between visual cells inside and outside the SCN. The visual properties of SCN cells have previously been investigated in hamsters and rats, both nocturnal species. Hypothalamic cells in all 3 species were similar in that they showed predominantly sustained responses to retinal illumination. The diurnal squirrel differed from the other two species in that there was a higher proportion of photically suppressed cells in the squirrel, and in that higher light intensities were required to stimulate photically responsive neurons.

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PubMed1989

Hamster circadian rhythms are phase-shifted by electrical stimulation of the geniculo-hypothalamic tract.

The suprachiasmatic nuclei (SCN) contain the major pacemaker for mammalian circadian rhythms. The SCN receive photic input both directly, via the retinohypothalamic tract (RHT), and indirectly, via the geniculohypothalamic tract (GHT), which originates in cells in the intergeniculate leaflet (IGL) and anterior portions of the ventral lateral geniculate nucleus (vLGN). We tested whether electrical stimulation of the GHT would induce phase shifts in wheel-running activity rhythms of Syrian hamsters housed in continuous darkness or continuous illumination. In both lighting conditions, electrical stimulation of the GHT induced mainly phase advances when given during the late subjective day and small phase delays when given during the late subjective night and early subjective day. Stimulation in the thalamus outside the GHT failed to produce similar phase shifts. Repeated daily stimulation had only a weak entraining effect on the activity rhythm. Activation of GHT neurons appears to influence the pacemaker for activity rhythms in a phase-dependent manner.

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PubMed1989

Photic responses of geniculo-hypothalamic tract neurons in the Syrian hamster.

The putative neural pacemaker controlling circadian rhythms in mammals is contained in the suprachiasmatic nuclei of the hypothalamus. These nuclei receive a projection, the geniculo-hypothalamic tract (GHT), from neurons in the intergeniculate leaflet (IGL) and portions of the ventral lateral geniculate nucleus (vLGN) of the thalamus. We examined the responses of putative GHT neurons to diffuse illumination using extracellular electrophysiological recordings. The great majority of IGL neurons showed sustained ON responses to diffuse retinal illumination; vLGN neurons showed more variation in their responses. Discharge rates of sustained ON neurons increased monotonically as light intensity was increased and saturated over 2-3 log units of intensity changes. Many IGL neurons had binocular input, and input from the ipsilateral eye was often inhibitory. These results indicate that GHT neurons may provide information about ambient light intensity to the suprachiasmatic nuclei.

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PubMed1989

The mammalian circadian system: models and physiology.

Mammalian circadian rhythms have been studied in great detail using primarily two different methods. One method is usually referred to as the formal analysis of rhythms. Its goal is to describe the properties of both rhythms and their underlying mechanisms, and it aims at the development of adequate mathematical models of the circadian system. The other method is the physiological analysis of the mechanisms that generate and entrain rhythms. Its goal is the identification of the anatomical components of the circadian system and the elucidation at a cellular and molecular level of how these components work. This paper reviews how the formal analysis of circadian systems, primarily in rodents, set the agenda for physiological studies, and the degree to which this agenda has been fulfilled. It then discusses how physiological analyses of the system have helped to redefine issues such as the nature and identity of the pacemaker, the nature of the entrainment process, the roles of photic and nonphotic cues, and the role of feedback in the circadian system. The continued commerce between these two approaches has led to a sophisticated appreciation of the complexities and subtleties of circadian organization in mammals. The further integration of formal and physiological analyses remains a challenging goal for the future.

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PubMed1988

Daily hoarding opportunity entrains the pacemaker for hamster activity rhythms.

The effects on activity rhythms of a daily 30 min opportunity to leave the home cage and hoard seeds from an open field were assessed in Syrian hamsters housed in continuous dim illumination. Six of ten hamsters responded with clear entrainment of their activity rhythms to the hoarding opportunity, as demonstrated by responses to phase shifts and by the onset phase of subsequent freerunning rhythms. No entrainable component separate from the freerunning rhythm was ever observed. Two hamsters showed phase shifts in response to the hoarding opportunity, but they did not meet the criteria for stable entrainment, and two did not respond with noticeable changes in rhythmicity. Ablations of the suprachiasmatic nuclei (SCN) were attempted in three hamsters that had entrained stably to the hoarding time. The effects of partial lesions in two animals indicated that the entrained rhythm was controlled by the light-entrainable pacemaker represented by the SCN. The one animal with an apparently complete lesion, however, developed a clear, but irregular, increase in activity in anticipation of the daily hoarding time. SCN ablation apparently unmasked an oscillator system separate from the SCN and susceptible to entrainment by a nonphotic cue. The oscillator mechanism affected by daily hoarding opportunities in hamsters appears to be tightly coupled to the SCN pacemaker, in contrast to the system in rats that is synchronized by daily feeding schedules.

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PubMed1988

Ablation of the geniculo-hypothalamic tract alters circadian activity rhythms of hamsters housed under constant light.

Retino-recipient cells in the hamster lateral geniculate nucleus project to the suprachiasmatic nucleus via the geniculo-hypothalamic tract (GHT). GHT-ablation alters phase advance shifts to light pulses in a hamster's late subjective night. In this study, the effects of GHT-ablation on wheel-running rhythms of hamsters housed under continuous illumination (LL) were assessed. In the first experiment, hamsters received GHT-ablation or sham surgery while under a light:dark schedule and were subsequently exposed to 250 days of LL. GHT-ablated hamsters showed rhythms with shorter periods and were less likely to show split activity rhythms than sham-operated or partial-lesion controls. In the second experiment, hamsters were housed under LL until rhythms split into two components; hamsters then received either GHT-ablation or sham surgery. Four of seven GHT-ablated hamsters showed re-fusion of their activity pattern into one component, while none of the eight sham-operated animals showed such re-fusion. The results of these two experiments indicate that GHT-ablation alters the responsiveness of the activity rhythm pacemaker to LL exposure.

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PubMed1988

Interactive effects of stress and photoperiod history on gonadal condition in male Syrian hamsters.

A study of the effects of melatonin injections given to male Syrian hamsters (Mesocricetus auratus) late in the light phase in a 14L:10D photoperiod included control, oil-injected hamsters that had been transferred from a 16L:8D photoperiod. Many oil-injected hamsters underwent gonadal regression under these conditions. A literature review indicated that endocrine effects of 'control' injections are fairly common but that they might depend on previous photoperiodic history. A second study found that hamsters born and raised in 16L:8D had larger testes at 150 days of age than those raised in 14L:10D. Transfer from 16L:8D to 14L:10D caused some unhandled hamsters to show gonadal regression while transfer to 14L:10D combined with daily oil injections caused most hamsters to undergo gonadal regression. Injections in animals maintained in 14L:10D throughout the study did not cause gonadal regression. These results indicate that stress effects can confound interpretation of drug treatments that require daily injections. They also demonstrate that the endocrine system of male Syrian hamsters distinguishes two photoperiods that are longer than the critical daylength (12.5 h). The effects of shortening daylengths may be potentiated by environmental stressors; together these may trigger gonadal regression at variable annual phases in anticipation of the critical daylength.

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PubMed1987

Electrophysiological responses of hamster suprachiasmatic neurones to neuropeptide Y in the hypothalamic slice preparation.

The rate and pattern of neuronal discharge in the hamster suprachiasmatic nucleus (SCN) was studied using an in vitro hypothalamic slice preparation. The firing rate of hamster SCN neurones (n = 183 cells) exhibited a circadian variation similar to that reported in the rat. SCN neurones tested for responses to pressure ejection of neuropeptide Y (NPY) (n = 49) were either tonically excited (65%) or unresponsive (35%). There was a tendency for more NPY-responsive cells to be recorded during the light phase of the circadian light-dark cycle.

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PubMed1987

Double-labeling of neuropeptide Y-immunoreactive neurons which project from the geniculate to the suprachiasmatic nuclei.

A projection from the ventral geniculate area to the suprachiasmatic nuclei (SCN) has been demonstrated in rats and hamsters. Large lesions in this area of the geniculate cause a dramatic decrease in neuropeptide Y-immunoreactivity in the SCN. Since numerous neuropeptide Y-immunoreactive neurons are found in the lateral geniculate area, we and others proposed that these immunoreactive neurons project to the SCN. In the present study, neurons in the lateral geniculate area of golden hamster brains were examined for both neuropeptide Y-immunoreactivity and a retrograde tracer transported from the SCN. Two days after a pressure injection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the SCN of hamsters, labeled neurons were found in the intergeniculate leaflet and in the external lamina of the anterior ventral lateral geniculate nucleus (VLGN). These neurons were compared with similarly located neurons which showed immunoreactivity for neuropeptide Y. Morphometric comparisons of neuropeptide Y- and WGA-HRP-labeled neurons indicated that they were comparable in terms of soma size, number of dendrites, orientation and location. In additional hamsters, neurons double-labeled with a retrograde tracer and neuropeptide Y-immunoreactivity were localized in the intergeniculate leaflet and in the external lamina of the anterior VLGN. These results demonstrate that many neuropeptide Y-immunoreactive neurons located in both the intergeniculate leaflet and in the external lamina of the anterior VLGN project to the SCN in hamsters.

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PubMed1987

Palatable daily meals entrain anticipatory activity rhythms in free-feeding rats: dependence on meal size and nutrient content.

Circadian wheel-running rhythms were monitored continuously in 3 groups of female Sprague-Dawley rats under different palatable food availability schedules. All rats had free access to standard rat chow and water throughout the study. In addition, Group 1 rats received a palatable nutrient-rich mash for 2 hr each day for 28 days, beginning 3 hr after light onset of a 12:12 LD cycle. Group 2 rats received the same mash but were limited to 4 g daily. Group 3 rats received a palatable non-nutritive mash. Ten of 13 Group 1 rats, 2 of 13 Group 2 rats, and 0 of 13 Group 3 rats showed anticipatory running prior to the daily palatable meal. Palatable mash intake was generally lower among Group 3 rats than among Group 1 rats. However, several Group 3 rats consumed non-nutritive mash in amounts which equalled or exceeded the nutritive mash intake of Group 1 rats showing anticipatory running. The results indicate that temporally limited daily access to a palatable food can entrain anticipatory wheel-running in rats that are not food-deprived. They also indicate that entrainment to periodic food availability depends on stimuli associated with the concentrated intake of nutrients rather than on the absolute size or palatability of a meal.

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PubMed1986

Carbachol phase shifts circadian activity rhythms in ovariectomized rats.

Ovariectomy in the rat abolishes alpha-bungarotoxin (alpha-BTX) binding within the suprachiasmatic nucleus (SCN), a putative circadian pacemaker, and markedly reduces cholinergic activation of SCN cells. Circadian rhythms of running wheel activity were monitored continuously in intact male and female and chronically ovariectomized rats before and after intraventricular carbachol injections. Carbachol produced similar phase shifts of the free-running rhythms in all groups. The results suggest that carbachol can influence the circadian system of rats by activation of cholinergic receptor sites independent of those binding alpha-BTX within the SCN.

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PubMed1986

Luminance coding in a circadian pacemaker: the suprachiasmatic nucleus of the rat and the hamster.

The hypothalamic suprachiasmatic nuclei (SCN) of mammals function as a pacemaker driving circadian rhythms. This pacemaker is entrained to the daily light-dark cycle in the environment via the retina and central retinal projections to the anterior hypothalamus. We carried out a comparative study of the visual properties of rat and hamster SCN neurons. Extracellular single cell activity was recorded in the SCN of urethane-anaesthetized animals. In both species, visual SCN neurons responded to retinal illumination with a sustained increase or a sustained decrease in electrical discharge. The majority (75%) of these cells were activated by light. In both the rat and the hamster SCN, visually responsive cells altered their discharge rate as a monotonic function of luminance. The intensity-response curve could be described by a Michaelis function with a small working range between threshold and saturation (2-3 log units) and a relatively high threshold. Intensity-response curves in both species were occasionally different for increasing as opposed to decreasing luminance. Thus, hysteresis effects of illumination may occur in the SCN. The spontaneous firing rates as well as the responsiveness of visual SCN cells were subject to marked variations between and within cells. The overall photic responsiveness of SCN neurons, however, indicated that they are specialized for luminance coding in the range of light intensities naturally occurring at dawn and dusk. This property makes these cells suitable to mediate photic entrainment of circadian rhythms as well as the measurement of photoperiod.

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PubMed1986

Lesions of the thalamic intergeniculate leaflet alter hamster circadian rhythms.

We have investigated the effects of destruction of the geniculo-hypothalamic tract (GHT) on the circadian system of golden hamsters. In the first experiment, intact hamsters were housed in constant darkness, and phase shifts in running-wheel activity rhythms were assessed following 15-min light pulses administered at circadian time (CT) 12 (defined as the beginning of activity), CT 14, CT 18, and CT 20. Responses to light pulses at the same CTs were then reassessed after GHT lesions. Hamsters with complete lesions showed decreases in phase advances caused by light pulses at CT 18 and CT 20. Phase delays elicited by light at CT 12 and CT 14 were not altered. In a second study, intact and GHT-ablated hamsters housed in constant light received 6-hr dark pulses at various CTs. Hamsters with complete GHT ablation showed smaller advances than controls to dark pulses centered on CT 8-10. After 110 days in constant light, 7 of 10 intact hamsters showed splitting of their activity rhythms into two components, while only 1 of the 8 similarly treated ablated hamsters displayed dissociated activity components. Ablated hamsters had significantly shorter free-running periods during the first 35 days of exposure to constant light than did the intact hamsters. These results demonstrate that destruction of the GHT in the hamster alters phase shifting in response to periods of light or dark, and they indicate a role for the GHT in mediating several photic effects on the circadian system.

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