Biomedical subjects

B Rusak

Publications and source records attributed to B Rusak.

At least 55 records · Page 3Linked to original sources

PubMed1994

Effects of ionophoretically applied bombesin-like peptides on hamster suprachiasmatic nucleus neurons in vitro.

Ionophoresis of the smaller bombesin-like peptides (gastrin releasing peptide [GRP]-(18-27), neuromedin B, and bombesin) evoked responses from 30-60% of hamster suprachiasmatic nucleus cells recorded in a hypothalamic slice preparation, depending on the circadian phase. We also demonstrated for the first time that the putative bombesin-like peptide receptor antagonists [D-F5,D-Phe6,D-Ala11]bombesin-(6-13)methyl ester (BIM 26226) and [D-Phe6,Des-Met14]bombesin-(6-14)ethyl amide can be applied ionophoretically to block physiological responses to bombesin-like peptides. Together with earlier findings, these results show that bombesin-like peptides administered by several methods can potently alter the firing rates of hamster suprachiasmatic nucleus neurons in vitro. These results indicate that bombesin-like peptides affect suprachiasmatic nucleus cells and could play a role in modulating suprachiasmatic nucleus-mediated circadian rhythm entrainment.

Animals↗

PubMed1994

Effects of serotonergic agonists on firing rates of photically responsive cells in the hamster suprachiasmatic nucleus.

Serotonergic neurons from the midbrain raphe nuclei innervate the suprachiasmatic nucleus (SCN) of the hypothalamus, which functions as the dominant pacemaker for mammalian circadian rhythms. We investigated the effects of serotonin (5-HT) on firing rates of light-activated SCN cells in urethane-anesthetized hamsters. Micro-iontophoretic application of 5-HT or 5-HT1A agonists (8-OH-DPAT and 5-CT) caused a dose-dependent inhibition of spontaneous activity and photic responses in the majority of SCN cells tested. Application of metergoline alone, a non-selective 5-HT antagonist, slightly increased firing rates during darkness and light exposure, suggesting a tonic serotonergic suppression of SCN activity. Metergoline also effectively attenuated suppression induced by the three 5-HT agonists. In addition, the effects of 8-OH-DPAT were blocked by a 5-HT1A antagonist, SDZ 216-525. However, other putative 5-HT antagonists were weak (propranolol and NAN-190) or ineffective (ketanserin) in blocking the action of 8-OH-DPAT. These results indicate that serotonin has a potent role in reducing photic effects on retinally activated SCN cells in hamsters, and that these effects are mediated by a receptor with properties similar to those of the 5-HT1A subtype.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1994

Physiological mechanisms regulating photic induction of Fos-like protein in hamster suprachiasmatic nucleus.

Immediate early genes including c-fos are selectively induced in cells of the hamster suprachiasmatic nucleus (SCN) by nocturnal light stimulation, suggesting that the Fos protein may play a role in the photic entrainment of circadian rhythms. To examine the physiological regulation of the induction of c-fos in the SCN, we studied the effects of antagonists of excitatory amino acids (EAA) receptors on photic induction of Fos-like immunoreactivity (Fos-lir) in the hamster SCN. We also examined the effects of electrical stimulation of the intergeniculate leaflet (IGL) to see whether neural input from IGL to SCN is involved in the induction of Fos protein in SCN cells. The results indicate that for most SCN cells EAA receptors mediate photic input involved in Fos induction but that another mechanism affects cells in restricted area of the caudal SCN. The neurochemical mechanisms and pathways by which these cells are activated by light remain undetermined.

Animals↗

PubMed1994

Activation of Fos-like immunoreactivity in the medial preoptic area and limbic structures by maternal and social interactions in rats.

The researchers examined the number of cells showing Fos-like immunoreactivity (Fos-lir) in the brains of hormonally primed parturient rat dams immediately following their first behavioral interactions with pups. Groups were exposed to newborn pups (pup), adult conspecifics (social), or a new food (food), or they were left alone in cages (control/isolate) for a 1-hr period. Rats were then killed, and their brains were prepared for immunohistochemical detection of Fos-lir. Rats in the pup group had higher numbers of cells showing. Fos-lir within the medial preoptic area (MPOA) nuclei than did the social, control/isolate, and, marginally, food groups and higher levels of Fos-lir in a number of amygdaloid nuclei (medial and cortical) and in cingulate and somatosensory cortices than did control/isolate or food groups. Fos-lir in amygdala did not differ between pup and social groups. There were also group differences in Fos-labeling in the olfactory bulbs, with the pup group showing the highest densities. These results show elevated expression of Fos-lir in brain structures that were activated during the expression of maternal behavior, including the olfactory structures, amygdala, and MPOA.

Amygdala↗

PubMed1993

Effects of serotonin agonists and melatonin on photic responses of hamster intergeniculate leaflet neurons.

Retinal input to the suprachiasmatic nuclei (SCN) and the intergeniculate leaflet (IGL) is involved in photic entrainment of mammalian circadian rhythms. The activating effects of light on firing rates of IGL cells may be regulated by serotonin (5-HT), since the IGL receives a dense serotonergic input from the midbrain raphe. We investigated the effects of 5-HT agonists and melatonin (a derivative of 5-HT) on single-unit discharges of light-sensitive cells in the hamster IGL area, using a microiontophoretic technique. 5-HT and a 5-HT1A-selective agonist, 8-OH-DPAT, potently suppressed both spontaneous and light-induced activity of IGL cells in a dose-related manner. This suppression was unchanged or potentiated by concurrently applied Mg2+, suggesting a direct action. Furthermore, the suppressive effects of both agonists were antagonized by a nonselective 5-HT antagonist, metergoline, and a 5-HT1A-directed antagonist, pindobind-5-HT1A. However, other putative 5-HT1A antagonists were weak (propranolol) or ineffective (pindolol and spiperone) in blocking the effects of 8-OH-DPAT. Neither of two 5-HT2 antagonists tested was able to block the effects of 5-HT. Melatonin generally mimicked the effects of 5-HT agonists on IGL cells, but these effects were not attenuated by 5-HT antagonists. The results indicate that both 5-HT and melatonin exert inhibitory effects on spontaneous activity and photic responses of cells in the hamster IGL, and that these effects are mediated via a 5-HT1A-like receptor and a melatonin receptor, respectively.

Action Potentials↗

PubMed1993

Daily variation in active glycogen phosphorylase patches in the molecular layer of rat dentate gyrus.

A larger number of discrete patches of active glycogen phosphorylase (alpha GP) were found in the molecular layer of the hippocampal dentate gyrus in rats sacrificed during the daily dark phase (mean = 28.7/section) than during the light phase (mean = 7.8/section). Light-dark differences in the patterns of alpha GP may reflect circadian differences in metabolic demand in the hippocampus. Patch sizes were consistent with increased activation of single astrocytes or perisynaptic astrocyte clusters by focal input at night.

Animals↗

PubMed1993

Localization of cholinergic neurons in the forebrain and brainstem that project to the suprachiasmatic nucleus of the hypothalamus in rat.

In mammals, the suprachiasmatic nucleus is responsible for the generation of most circadian rhythms and their entrainment to environmental cues. Cholinergic agents can alter circadian rhythm phase, and fibres immunoreactive for choline acetyltransferase, the biosynthetic enzyme for acetylcholine, are present in the suprachiasmatic nucleus. Since there are no cholinergic somata in the suprachiasmatic nucleus, these fibres must represent the terminals of cholinergic neurons whose cell bodies are located elsewhere in the brain. This study was aimed at locating the cholinergic neurons that project to the suprachiasmatic nucleus by retrograde and anterograde tract-tracing and immunohistochemistry for choline acetyltransferase in the rat. After injection of fluorogold, a retrograde tracer, into the suprachiasmatic nucleus, retrogradely labelled neurons that were immunopositive for choline acetyltransferase were located throughout the rostrocaudal extent of the cholinergic basal nuclear complex, with highest densities in the substantia innominata and the nucleus basalis magnocellularis. A few cells were also located in the medial septum and in the vertical and horizontal limbs of the diagonal band of Broca. In the brainstem, double-labelled neurons were located in the laterodorsal tegmental nucleus, pedunculopontine tegmental nucleus and the parabigeminal nucleus. Injections of the anterograde tracer biocytin in these three brainstem nuclei resulted in fibre labelling in the suprachiasmatic nucleus, consistent with the retrograde findings. No clearly double-labelled cells were located in the retina. These results suggest that the suprachiasmatic nucleus receives cholinergic afferents from both the basal forebrain and mesopontine tegmentum which may mediate cholinergic effects on circadian rhythms.

Animals↗

PubMed1993

Regulation of melatonin-sensitivity and firing-rate rhythms of hamster suprachiasmatic nucleus neurons: constant light effects.

Rhythms of spontaneous firing rate and of responsiveness to pressure ejection of melatonin were recorded from neurons in the Syrian hamster suprachiasmatic nuclei (SCN) in a slice preparation. In animals taken from light-dark cycles (LD 14:10), SCN cells had high firing rates during the projected day and lower rates during the projected night. The proportion of melatonin-suppressed cells (35% overall) was also high during the day and fell during the night, while melatonin activated approximately 23% of cells at all phases. To assess the source of the melatonin-responsiveness rhythm, hamsters were exposed for approximately 48 h to constant illumination (LL) to suppress melatonin secretion. LL exposure before slice preparation altered both firing-rate and melatonin-responsiveness rhythms. Firing rates failed to show a morning peak and remained at low levels, with no indication of daily rhythmicity. Melatonin responsiveness also failed to show the usual rhythm and even tended to rise at night. Overall melatonin responsiveness rose after LL exposure so that 50% of cells were suppressed and 21% activated. LL exposure also increased the proportions of cells which showed regular baseline firing rates. Control studies indicated that pressure artifacts did not account for either suppression or activation by melatonin, while the composition of the saline vehicle appeared to be responsible for the activations recorded. The results indicate that brief LL exposure alters SCN sensitivity to melatonin and SCN rhythmicity in Syrian hamsters, perhaps as a result of the loss of the daily melatonin secretion rhythm. Physiological melatonin patterns may have important effects on the rodent circadian pacemaker.

Animals↗

PubMed1993

Regulation of melatonin-sensitivity and firing-rate rhythms of hamster suprachiasmatic nucleus neurons: pinealectomy effects.

As a test of the origin of the melatonin-sensitivity rhythm recorded from SCN cells in brain slices from intact Syrian hamsters, hamsters were either pinealectomized to remove the influence of endogenous melatonin, or sham operated. Cells from sham-operated hamsters showed a trough in responsiveness during the projected night. Pinealectomy eliminated the daily rhythm of melatonin responsiveness, reduced the proportions of cells responding to melatonin, and raised response thresholds in those cells that did not meet the criterion for responsiveness. Pinealectomy also altered the firing-rate rhythm so that the morning peak in firing rate was not sustained and the nocturnal trough was attenuated, leading to a firing-rate rhythm with reduced amplitude compared to those recorded from sham-operated or intact animals. These results indicate a role for endogenous melatonin in regulating both melatonin sensitivity and the integrity of the SCN firing-rate rhythm, and they suggest why pinealectomy can disrupt circadian organization in some situations.

Animals↗

PubMed1993

Electrophysiological effects of pressure-ejected bombesin-like peptides on hamster suprachiasmatic nucleus neurons in vitro.

The suprachiasmatic nuclei (SCN) of the rodent hypothalamus function as a light entrainable circadian pacemaker. The SCN contain moderate to high concentrations of a number of neuropeptides including peptides showing structural homology with the amphibian derived tetradecapeptide, bombesin (BN), called bombesin-like peptides (BNLPs). BNLPs include the 27 amino acid peptide, gastrin releasing peptide (GRP1-27), a smaller decapeptide (GRP18-27) and another decapeptide with less structural homology, neuromedin B (NmB). Immunoreactivity for BN and receptors for BNLPs have been demonstrated in the region of the rat SCN receiving photic input. We studied the effects of local pressure ejections of BNLPs dissolved in saline/1% bovine serum albumin (BSA) vehicle on the extracellularly recorded firing rates of Syrian hamster SCM neurons in a hypothalamic slice preparation. In one study, an ejecting electrode containing BN (10(-8) to 10(-4) M) was positioned 20 to 60 microm from a recording electrode. Of 74 cells tested with BN, 50 (67.6%) showed significant increases in firing rate, while 3 of 29 cells (15.8%) tested with vehicle ejections were activated. In a second study, a single electrode was used for both recordings and pressure ejections. Of 48 cells tested, BN (10(-6) to 10(-4) M) activated 30 (62.5%) and suppressed firing in 4 (8.3%). Of 208 cells tested with GRP1-27 (10(-9) to 10(-4) M), 105 (50.5%) were activated and 2 (1.0%) were suppressed. The percentage of cells responding increased with the concentration of GRP1027 used in the electrode. No circadian variation in responsiveness to GRP1-27 was detected. GRP18-27 (5 x 10(-5) to 10(-4) M) activated 10 out of 18 cells tested (55.6%), while NmB (10(-4) M) activated 2 out of 30 cells tested (6.7%) and vehicle ejections activated 1 out of 36 cells tested (2.8%). GRP1-27, GRP18-27 and BN, the BNLPs showing the greatest degree of structural homology, activate approximately 50% of SCN cells, apparently via the BN/GRP-preferring receptor subtype, and may play a role in photic entrainment.

Amino Acid Sequence↗

PubMed1993

Neurophysiological analysis of circadian rhythm entrainment.

We review recent studies in our laboratory that have investigated the neural mechanisms underlying photic entrainment of the mammalian circadian system. The results from studies of extracellular single-unit recordings and of photic induction of Fos-like immunoreactivity (Fos-lir) indicate that excitatory amino acid (EAA) transmission, and particularly activation of the N-methyl-D-aspartate (NMDA) receptor subtype, is important for conveying photic information to suprachiasmatic nucleus (SCN) cells. We have also found that a subregion of the SCN still shows Fos-lir after blockade of EAA receptors, and we have evidence suggesting that these cells are innervated by a distinct subdivision of the retinal projection to the SCN. In addition, we have found that photic responses of cells in the intergeniculate leaflet (which projects to the SCN) and of SCN cells are modulated by serotonin (5-HT) via a receptor that resembles the 5-HT1A subtype.

Animals↗

PubMed1992

Stimulation of the hamster ventral lateral geniculate nucleus induces Fos-like immunoreactivity in suprachiasmatic nucleus cells.

The suprachiasmatic nucleus (SCN) functions as a pacemaker for circadian rhythms in rodents. Its activity and, therefore, circadian rhythms, are synchronized by light information from both a direct retinal projection and an indirect projection from the thalamic intergeniculate leaflet (IGL) and ventral lateral geniculate nucleus (vLGN) (geniculohypothalamic tract; GHT). The GHT also appears to be important for synchronizing circadian rhythms to non-photic cues. Light can activate expression of several immediate-early genes in the SCN, including c-fos. We examined whether electrical stimulation of the IGL/vLGN region would induce Fos-like immunoreactivity (lir) in the hamster SCN. Electrical stimulation was given for one hour during the dark period of the lighting cycle. Stimulation at night of the IGL and adjacent LGN regions induced Fos-lir in cells in the SCN. Labeled cells were found in the dorsolateral part of the caudal SCN, and not in rostral or central regions of the SCN, nor in the ventral part of the caudal SCN. These results indicate that activation of cells contributing to the hamster GHT can induce Fos-lir in a restricted region of the caudal SCN.

Animals↗

PubMed1992

The relation between light-induced discharge in the suprachiasmatic nucleus and phase shifts of hamster circadian rhythms.

The role of neurophysiological activation of suprachiasmatic nucleus (SCN) cells in phase shifting the circadian pacemaker of the hamster was investigated in a combined behavioural and electrophysiological study. An electrophysiological study examined the relation between the pattern of light presentation and the induced discharge rate in the SCN. Behavioural experiments examined the relation between the pattern of light presentation and the magnitude of phase shift induced. The combination of these results provides an indirect assay of the relations between induced neural discharge in the SCN and phase shifts of the circadian activity rhythm. The data indicate that the magnitude of phase shifts is monotonically, but not linearly, related to photically induced changes in discharge rate.

Action Potentials↗

PubMed1992

Circadian variation in photic regulation of immediate-early gene mRNAs in rat suprachiasmatic nucleus cells.

Exposure of rodents to light at daily times at which it can phase-shift circadian rhythms (subjective night) induces an increase in immunoreactivity for the immediate-early gene product Fos in cells of the circadian pacemaker, the suprachiasmatic nuclei (SCN). Light exposure at other phases (subjective day) does not increase Fos immunoreactivity in SCN cells, but it is not known whether this failure reflects the inability of light to induce transcription of appropriate mRNAs, or a post-transcriptional block. We used in situ hybridization studies to examine levels of mRNA in the SCN of rats exposed to light during the subjective day and subjective night. We studied levels of mRNAs for several immediate-early genes: c-fos, NGFI-A, NGFI-B, c-jun, junB and junD, before and after light exposure at these phases. Levels of mRNAs for all of the genes tested were unaffected by light exposure during the subjective day, and all were increased in response to light during the subjective night. With the exception of a weak constitutive label for junD, none of the genes were expressed in the SCN in darkness at either phase. Light-induced increases in the levels of several mRNAs in the SCN occur only during the subjective night; the mechanisms which prevent such responses during the subjective day remain unknown.

Animals↗

PubMed1992

NMDA and non-NMDA receptor antagonists inhibit photic induction of Fos protein in the hamster suprachiasmatic nucleus.

We previously reported that systemic treatment with a noncompetitive antagonist affecting the NMDA subtype of excitatory amino acid (EAA) receptor, MK-801, inhibits photic induction of Fos-like immunoreactivity (Fos-lir) in the hamster suprachiasmatic nucleus (SCN). Because MK-801 blocks the Ca2+ channel associated with the NMDA receptor, it may also influence the activity of other transmitters acting through Ca2+ channels. To assess the specificity of these effects, we compared the effects on photic induction of Fos-lir of several treatments: central injection of a competitive NMDA antagonist, CPP; central injection of a non-NMDA antagonist, DNQX; and systemic injection of the non-competitive NMDA antagonist, ketamine. Fos-lir was induced in SCN cells of vehicle-injected hamsters exposed to a light pulse 4-5 h after dark onset. Pretreatment with CPP (greater than 2 nmoles) or ketamine (greater than 100 mg/kg) caused a dose-related inhibition of photic induction of Fos-lir in portions of the SCN. These treatments reduced Fos-lir mainly in the rostral SCN and ventrolateral, but not dorsolateral, portions of the caudal SCN. Pretreatment with DNQX (greater than 20 nmoles) also inhibited photic induction of Fos-lir in the same regions of the SCN. These results indicate that photic induction of Fos protein in a portion of the hamster SCN is regulated by both NMDA and non-NMDA types of EAA receptor.

Animals↗

PubMed1992

Anticipatory activity and entrainment of circadian rhythms in Syrian hamsters exposed to restricted palatable diets.

Activity rhythms were recorded from hamsters in three conditions: during timed feedings of an attractive diet with free access to regular food, during restriction to 70% of normal food consumption, and during moderate food deprivation with limited temporal access to an attractive diet. An attractive diet given to intact animals did not induce anticipatory activity or entrainment, but damage to the suprachiasmatic nuclei (SCN) led to the development of anticipatory activity. Food restriction to 70% of normal intake led to anticipatory components in some intact animals, without entraining the dominant circadian pacemaker. The combination of a palatable diet and food restriction led to anticipatory activity before the daily feeding times and entrainment of a previously free-running circadian rhythm in some animals. Ablation of the SCN did not eliminate anticipatory activity in experimental animals, but did eliminate the free-running component of the rhythms. These results indicate that hamsters have a mechanism separate from the SCN that can anticipate daily feeding times, as rats do, and that they may show entrainment of the SCN-based pacemaker to such feeding schedules.

Activity Cycles↗

PubMed1991

Luminance coding properties of intergeniculate leaflet neurons in the golden hamster and the effects of chronic clorgyline.

Cells in the intergeniculate leaflet (IGL) project to the suprachiasmatic nuclei, a mammalian circadian pacemaker. Chronic treatment with clorgyline alters hamster circadian rhythms in ways similar to alterations seen after ablation of the IGL. Chronic clorgyline also alters the light intensity dependence of phase-shifting. In this study luminance coding properties of IGL cells were measured in control hamsters and in hamsters chronically treated with clorgyline. In control animals three patterns of response to increasing and decreasing luminance were observed. Type I cells showed a monotonic pattern. Type II cells were similar to Type I with additional increases in firing rate at several specific luminance levels. Type III cells only coded increases in luminance. Cells from clorgyline-treated animals did not differ from those from control animals in the pattern of luminance response but IGL cells from these animals showed decreased firing rate in both light and dark conditions. These results suggest that the effects of clorgyline on the photic sensitivity of circadian rhythms may be related to a clorgyline-induced decrease in firing rate of IGL cells. They also indicate that some IGL cells show complex patterns of response to luminance changes in addition to those showing simple monotonic responses.

Animals↗

PubMed1991

Photic induction of Fos protein in the suprachiasmatic nucleus is inhibited by the NMDA receptor antagonist MK-801.

Exposure of rodents to light can induce expression of a number of immediate-early genes, including c-fos, in cells of the suprachiasmatic nucleus (SCN), a dominant pacemaker in the mammalian circadian system. We examined the effects of pre-treatment with the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, on the induction of Fos-like immunoreactivity (Fos-lir) in cells in the hamster SCN. At doses of 3 and 5 mg/kg, MK-801 treatment blocked photic induction of Fos-lir in the rostral SCN and ventrolateral portions of the caudal SCN but failed to block induction of Fos-lir in a discrete region of the dorsolateral SCN. These results suggest that photic induction of Fos-lir in most of the SCN depends on activation of an NMDA-type receptor which is sensitive to MK-801, but that Fos-lir in one portion of the SCN is induced by a mechanism which is not antagonized by MK-801.

Animals↗