The ventral lateral geniculate nucleus and the intergeniculate leaflet: interrelated structures in the visual and circadian systems

The ventral lateral geniculate nucleus (vLGN) and the intergeniculate leaflet (IGL) are retinorecipient subcortical nuclei. This paper attempts a comprehensive summary of research on these thalamic areas, drawing on anatomical, electrophysiological, and behavioral studies. From the current perspective, the vLGN and IGL appear closely linked, in that they share many neurochemicals, projections, and physiological properties. Neurochemicals commonly reported in the vLGN and IGL are neuropeptide Y, GABA, enkephalin, and nitric oxide synthase (localized in cells) and serotonin, acetylcholine, histamine, dopamine and noradrenalin (localized in fibers). Afferent and efferent connections are also similar, with both areas commonly receiving input from the retina, locus coreuleus, and raphe, having reciprocal connections with superior colliculus, pretectum and hypothalamus, and also showing connections to zona incerta, accessory optic system, pons, the contralateral vLGN/IGL, and other thalamic nuclei. Physiological studies indicate species differences, with spectral-sensitive responses common in some species, and varying populations of motion-sensitive units or units linked to optokinetic stimulation. A high percentage of IGL neurons show light intensity-coding responses. Behavioral studies suggest that the vLGN and IGL play a major role in mediating non-photic phase shifts of circadian rhythms, largely via neuropeptide Y, but may also play a role in photic phase shifts and in photoperiodic responses. The vLGN and IGL may participate in two major functional systems, those controlling visuomotor responses and those controlling circadian rhythms. Future research should be directed toward further integration of these diverse findings.     

The role of the intergeniculate leaflet in entrainment of circadian rhythms to a skeleton photoperiod

Mammalian circadian rhythms are synchronized to environmental light/dark (LD) cycles via daily phase resetting of the circadian clock in the suprachiasmatic nucleus (SCN). Photic information is transmitted to the SCN directly from the retina via the retinohypothalamic tract (RHT) and indirectly from the retinorecipient intergeniculate leaflet (IGL) via the geniculohypothalamic tract (GHT). The RHT is thought to be both necessary and sufficient for photic entrainment to standard laboratory light/dark cycles. An obligatory role for the IGL-GHT in photic entrainment has not been demonstrated. Here we show that the IGL is necessary for entrainment of circadian rhythms to a skeleton photoperiod (SPP), an ecologically relevant lighting schedule congruous with light sampling behavior in nocturnal rodents. Rats with bilateral electrolytic IGL lesions entrained normally to lighting cycles consisting of 12 hr of light followed by 12 hr of darkness, but exhibited free-running rhythms when housed under an SPP consisting of two 1 hr light pulses given at times corresponding to dusk and dawn. Despite IGL lesions and other damage to the visual system, the SCN displayed normal sensitivity to the entraining light, as assessed by light-induced Fos immunoreactivity. In addition, all IGL-lesioned, free-running rats showed masking of the body temperature rhythm during the SPP light pulses. These results show that the integrity of the IGL is necessary for entrainment of circadian rhythms to a lighting schedule like that experienced by nocturnal rodents in the natural environment.     

Roles of suprachiasmatic nuclei and intergeniculate leaflets in mediating the phase-shifting effects of a serotonergic agonist and their photic modulation during subjective day

Serotonin (5-HT) has been implicated in the phase adjustment of the circadian system during the subjective day in response to nonphotic stimuli. Two components of the circadian system, the suprachiasmatic nucleus (SCN) (site of the circadian clock) and the intergeniculate leaflet (IGL), receive serotonergic projections from the median raphe nucleus and the dorsal raphe nucleus, respectively. Experiment 1, performed in golden hamsters housed in constant darkness, compared the effects of bilateral microinjections of the 5-HT1A/7 receptor agonist, 8-hydroxydipropylaminotetralin (8-OH-DPAT; 0.5 microgram in 0.2 microliter saline per side), into the IGL or the SCN during the mid-subjective day. Bilateral 8-OH-DPAT injections into either the SCN or the IGL led to significant phase advances of the circadian rhythm of wheel-running activity (p < .001). The phase advances following 8-OH-DPAT injections in the IGL were dose department (p < .001). Because a light pulse administered during the middle of the subjective day can attenuate the phase-resetting effect of a systemic injection of 8-OH-DPAT, Experiment 2 was designed to determine whether light could modulate 5-HT agonist activity at the level of the SCN and/or the IGL. Serotonergic receptor activation within the SCN, followed by a pulse of light (300 lux of white light lasting 30 min), still induced phase advances. In contrast, the effect of serotonergic stimulation within the IGL was blocked by a light pulse. These results indicate that the respective 5-HT projections to the SCN and IGL subserve different functions in the circadian responses to photic and nonphotic stimuli.     

Phosphoglycopeptide, a major constituent of the spermatophoric plasma of the octopus (Octopus dofleini martini)

A phosphoglycopeptide, accounting for approximately 90% of the characteristically high content of acid-soluble organically-bound phosphorus in the octopus spermatophoric plasma (4 mg P/ml), was identified. Electrophoretic and chromatographic purification, followed by chemical and enzymic hydrolysis, yielded D-galactose phosphate as a degradation product. The galactose and peptide moieties of the compound were linked via a phosphoryl rather than a glycosidic linkage but the peptide was devoid of aromatic amino acids.     

Fodrin is a constituent of the cortical lattice in outer hair cells of the guinea pig cochlea: immunocytochemical evidence

Localization of fodrin, a membrane skeletal protein, in the outer hair cell of the guinea pig cochlea was examined by immunocytochemical techniques. By immunofluorescence microscopy, fodrin was observed in the cuticular plate, in the infracuticular network and along the lateral wall. By immunoelectron microscopy of ultrathin cryosections, labeling for fodrin along the lateral wall was localized between the cell membrane and the outermost layer of the subsurface cisternae. Furthermore, pre-embedding immunoelectron microscopy of permeabilized specimens showed that most immunogolds for fodrin were on the thin cross-linking component of the cortical lattice. The results indicate that fodrin is a constituent of the cortical lattice which is thought to play an important role in outer hair cell motility.     

Morphine-naloxone interaction in the central cholinergic system: the influence of subcortical lesioning and electrical stimulation

1 The opiate antagonist naloxone, injected or topically applied to the cerebral cortex, had no significant effect on the spontaneous output of cortical acetylcholine (ACh) in rats. 2 Morphine (2.5 mg/kg) administered intravenously inhibited the release of cortical ACh. A subsequent injection of naloxone rapidly reversed morphine-induced inhibition, and produced a sustained increase in the release of ACh. Topical application of naloxone solutions, after morphine, produced a slow and weak reversal of its inhibitory action. 3 Destruction of the medial thalamus abolished both the inhibitory effects of morphine on the cortical ACh release, and its antagonism by naloxone administered after the agonist. 4 Injection of naloxone in a low dose (0.1 mg/kg) increased the release of cortical ACh provoked by electrical stimulation of either the medial thalamus or the reticular formation in normal rats. In the morphine-dependent rat, naloxone also facilitated the evoked release and its action was greater than in control animals. The facilitatory effect of naloxone on the cortical release evoked by stimulation of the medial thalamus was greater than its effect on the release evoked by stimulation of the reticular formation in both normal and morphine-dependent rats. 5 Naltrexone, a narcotic antagonist, also facilitated the electrically stimulated release of cortical ACh. 6 It is suggested that (a) morphine and naloxone act at a subcortical site, probably the medial thalamus, to modify the cortical ACh release and that (b) naloxone may facilitate the electrically-induced release of ACh in the CNS by antagonizing the effect of the endogenous morphine-like factor, enkephalin.     

An alternate pathway for visual signal integration into the hypothalamo-pituitary axis: retinorecipient intergeniculate neurons project to various regions of the hypothalamus and innervate neuroendocrine cells including those producing dopamine

Using tract tracing and immunocytochemistry, this study explored the connectivity between lateral geniculate efferents and neurons of the hypothalamus, including those producing dopamine, that have direct access to fenestrated capillaries. It was also determined whether the intergeniculate neurons that give rise to hypothalamic projections are targeted by retinal axons. Within the hypothalamus, Phaseolus vulgaris leucoagglutinin-labeled, lateral geniculate efferents were observed in the suprachiasmatic nucleus, subparaventricular area, periventricular nuclei, medial preoptic areas, and between the arcuate and ventromedial nuclei. In these sites, intergeniculate efferents contacted populations of neurons that were retrogradely labeled from fenestrated capillaries by the intraperitoneal injection of fluorogold. Hypothalamic dopamine neurons, a population of which was neuroendocrine, were also synaptic targets of lateral geniculate efferents. After injection of the retrograde tracer fluorogold into these hypothalamic projection sites in parallel with bilateral enucleation, retrogradely labeled perikarya were restricted to the intergeniculate leaflet. All of the labeled perikarya contained infolded nuclei, and their distal dendrites were frequently found to be contacted by degenerated, retinal fibers. This study provides morphological evidence for a signaling pathway from the retina through the intergeniculate leaflet to hypothalamic cells that participate in neuroendocrine regulations. These observations raise the possibility that visual signals independent of the circadian clock may also influence the hypothalamo-pituitary axis. In light of the overlapping distribution of intergeniculate and suprachiasmatic efferents in the hypothalamus and their similar relationship with neuroendocrine cells, it is suggested that integration of circadian and visual signals can occur outside of the suprachiasmatic nucleus to regulate endocrine rhythms.     

A retrograde fluorescent-labeling study of direct relationship between the limbic (anterodorsal and anteroventral thalamic nuclei) and the visual system in the albino rat

Case-control methodology was used to assess lung cancer risk from exposure to arsenic in air, employing data from former workers in different units at the Chuquicamata copper mine and smelter complex. Thirty two workers from this complex were identified among the lung cancer deaths that occurred in the Northern region of Chile between 1987 and 1991. Each case was matched on age and sex, with controls that had a similar date of enrolment in the company. Available data on arsenic concentrations in air for six work sites were compiled from 1952 to 1991 and these were used to categorize the workplaces: Administrative area (1.6 micrograms/m3), Mine (2.3 micrograms/m3), Oxid Plant (3.1 micrograms/m3), Workshop and Services (9.8 micrograms/m3), Sulphur Plant (8.4 micrograms/m3) and Smelter (201.7 micrograms/m3). The results indicate an Odds Ratio of 5.7 (Fisher's p = 0.016) of dying from lung cancer among workers of the smelter compared with the rest of the workers.     

Thrombopoietin, the c-mpl ligand, is a major regulator of platelet production

Hematopoiesis is regulated by a family of glycoproteins, the hematopoietic growth factors. Although the cytokines that influence the late stages of granulopoiesis (granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor) or erythropoiesis (erythropoietin) have been identified, characterized, and cloned, and have been in clinical use since that late 1980's, the cytokine that stimulates thrombopoiesis had remained elusive. By using strategies based on the c-mpl receptor, several groups have recently succeeded in purifying and cloning thrombopoietin [1-6]. This study outlines the cloning and biological characterization in vitro and in vivo of thrombopoietin, a major regulator of platelet production.     

Fibronectin lacking the ED-B domain is a major structural component of tracheal cartilage

Fibronectin is a highly conserved dimeric glycoprotein found in high concentrations in plasma and widely distributed in low concentrations in the extracellular matrix of tissues. The protein is the product of a single gene, but multiple splicing variants are expressed that show tissue specificity. Three exons (IIIA, IIIB, and V) can be alternatively spliced to produce different fibronectin isoforms. We report here that fibronectin is a remarkably abundant component of the extracellular matrix of bovine tracheal cartilage, increasing with age to more than 20% of the tissue, dry weight. This matrix form of fibronectin is inextractable by 4 M guanidine HCl, indicating that it is a covalently cross-linked structural component. By protein sequence analysis, the main molecular form of fibronectin in bovine tracheal cartilage was shown to lack the ED-B domain encoded by exon IIIB.     

Low dietary iron availability is a major cause of anemia: a nutrition survey in the Lindi District of Tanzania

Two years after upgrading its nursing programme to university level, Israel experienced a massive wave of immigration from the former Soviet Union. Previous studies have shown that Russian immigrants in general, and in nursing in particular, have several unique characteristics that need to be taken into consideration in planning curricula and absorption programmes. The aim of the present work was to update these data, focusing on the reasons new immigrants choose nursing as a career, their image of the profession and their satisfaction with it. The study population consisted of 302 students attending five major academic schools of nursing in Israel. Students were divided into two groups: new immigrants (less than 4 years in Israel) and long-time Israelis (more than 4 years in Israel). All completed a 30-item questionnaire of proven validity and reliability. Findings were analysed by length of time in Israel and year of study. Using a series of statistical tests, we found that compared with the long-time Israelis, the new immigrants came from a higher socio-economic/professional stratum (in their mother country), had a less 'technical' perception of nursing, and were attracted to the profession primarily for extrinsic reasons ('close to medicine', economics). Both groups showed highest satisfaction in the clinical domain; however, the difference was significant only in the long-time Israeli group, even though the new immigrants had rated this domain highest in importance. The new immigrants showed least satisfaction in the academic domain. These results could be explained by several factors: the financial and housing problems that accompany immigration; the higher proportion of married students in the new immigrant group; and especially language difficulties, which are multiplied in Israel, where mastery in both Hebrew and English is necessary. Of particular interest was the fact that many of the immigrant students had already begun or completed medical school in their old country but were forced to compromise their dreams on immigration. This affected both their image of nursing and their reasons for choosing it as a career. We believe these findings will help nurse educators identify areas in which they can help ease the absorption process for maximal benefit to both the students and the profession.     

Outcome and cost of trauma among the elderly: a real-life model of a single-payer reimbursement system

BACKGROUND: As our population ages, the number of elderly trauma patients (age > or = 65 years) increases. Studies have demonstrated increased mortality and cost for a given injury severity in the elderly compared with younger patients. The financial viability of trauma centers in the United States has been an area of concern for many years. As reimbursement diminishes for privately insured patients, the ability to finance the care of the indigent is jeopardized. Medicare, the single-payer insurance plan for the elderly, reimburses at a lower rate than standard private insurance carriers. We examined the differences in outcome and cost between the elderly and younger patients and the financial burden imposed by care for elderly trauma. Our hypothesis was that elderly trauma patients would have poorer outcomes, higher cost, and generate greater financial losses than younger patients. METHODS: All patients admitted to the University of Virginia Trauma Service from July 1, 1994, to July 1, 1997 were included. Trauma registry and patients records were examined. Patients with incomplete financial data (cost, reimbursement, and payer source) were excluded. Patients were grouped by age (18-64 and > or =65 years), Injury Severity Score, and payer source. RESULTS: One thousand one hundred twenty-seven patients met the entry criteria. One hundred forty patients had incomplete financial or patient data and were excluded. Nine hundred eighty-seven patients were included in the study, of which 159 were elderly and 828 were 18 to 64 years of age. Injury Severity Scores were significantly higher in the elderly group. Only 2% of elderly patients were uninsured (76% were insured by Medicare), whereas 25% of younger patients were uninsured. Medicare reimbursement rates actually exceeded those of all other carriers (114% of costs). Elderly patients had a higher mortality rate, but the z score did not reach significance. The W score, however, indicated that there were more unexpected, negative outcomes among elderly patients. As injury severity increased, profit per case increased in the elderly and decreased in the younger group. CONCLUSION: Despite higher injury severity and lower survival probability for the elderly, the length of hospital and intensive care unit stays, as well as the percentage of admissions to the intensive care unit, were similar. The per capita cost of hospital care for the elderly was lower than for younger patients, whereas reimbursement was higher, primarily because 98% of elderly patients were insured. Medicare, the single-payer insurance plan for the elderly, adequately reimburses for elderly trauma care. This implies that universal insurance coverage for all trauma patients would be desirable, even if reimbursement rates decreased significantly. The increased mortality in the elderly requires continued study and diligence.     

Versican V2 is a major extracellular matrix component of the mature bovine brain

We have isolated and characterized the proteoglycan isoforms of versican from bovine brain extracts. Our approach included (i) cDNA cloning and sequencing of the entire open reading frame encoding the bovine versican splice variants; (ii) preparation of antibodies against bovine versican using recombinant core protein fragments and synthetic peptides; (iii) isolation of versican isoforms by ammonium sulfate precipitation followed by anion exchange and hyaluronan affinity chromatography; and (iv) characterization by SDS-polyacrylamide gel electrophoresis and Coomassie Blue staining or immunoblotting. Our results demonstrate that versican V2 is, together with brevican, a major component of the mature brain extracellular matrix. Versicans V0 and V1 are only present in relatively small amounts. Versican V2 migrates after chondroitinase ABC digestion with an apparent molecular mass of about 400 kDa, whereas it barely enters a 4-15% polyacrylamide gel without the enzyme treatment. The 400-kDa product is recognized by antibodies against the glycosaminoglycan-alpha domain and against synthetic NH2- and COOH-terminal peptides. Our preparations contain no major proteolytic products of versican, e.g. hyaluronectin or glial hyaluronate-binding protein. Having biochemical quantities of versican V2 available will allow us to test its putative modulatory role in neuronal cell adhesion and axonal growth.     

Prevalence and correlates of major depressive episode among the elderly in a community in Japan

A random sample of 205 persons from a community of about 45,500 residents, aged 65 years or older, in a city in Japan, was surveyed using an interview schedule including a structured psychiatric interview to analyze prevalence of major depressive episode (DSM-III-R). A total of 157 (77%) participated in the study. Results were as follows: 1) The Prevalence of major depressive episode during the past 6 months was 2.1% for males and 3.7% for females among the 155 respondents who completed the psychiatric interview. 2) Significantly higher prevalence during the past 6 months was observed in those who were physically inactive in the past year than in those physically active (p < 0.05). 3) Levels of satisfaction with available social support were significantly lower in those who experienced major depressive episode during the past six months than in those who experienced no depressive episode (p < 0.05). 4) Levels of life satisfaction (PGC scale score) and cognitive functioning were significantly lower in those experienced major depressive episode during the past six months than in those who experienced no depressive episode (p < 0.05).     

Dementia is the major cause of functional dependence in the elderly: 3-year follow-up data from a population-based study

OBJECTIVES: The purpose of this investigation was to study the role of dementia and other common age-related diseases as determinants of dependence in activities of daily living (ADL) in the elderly. METHODS: The study population consisted of 1745 persons, aged 75 years and older, living in a district of Stockholm. They were examined at baseline and after a 3-year follow-up interval. Katz's index was used to measure functional status. Functional dependence at baseline, functional decline, and development of functional dependence at follow-up were examined in relation to sociodemographic characteristics and chronic conditions. RESULTS: At baseline, factors associated with functional dependence were age, dementia, cerebrovascular disease, heart disease, and hip fracture. However, only age and dementia were associated with the development of functional dependence and decline after 3 years. In a similar analysis, including only nondemented subjects. Mini-Mental State Examination scores emerged as one of the strongest determinants. The population attributable risk percentage of dementia in the development of functional dependence was 49%. CONCLUSIONS: In a very old population, dementia and cognitive impairment make the strongest contribution to both the development of long-term functional dependence and decline in function.