Cellular and nuclear morphology…and calcium signaling: revealing the interplay between structure and function

Poster presentation: Calcium plays a pivotal role in relaying electrical signals of the cell to subcellular compartments, such as the nucleus. Since this one ion type is used by the cell for many processes a neuron needs to establish finely tuned calcium pathways in order to be able to differentiate multiple tasks, [1-3]. While it is known that neurons can actively change their shape upon neuronal activity, [4-7], we here present novel findings of activity-regulated nuclear morphology, [8,9]. With the help of an experimental and computational modeling approach, we show that hippocampal neurons can change the previously spherical shape of their nuclei to complex and infolded morphologies. This morphology regulation is demonstrated to be regulated by NMDA-receptor gated calcium, while synaptic and extra-synaptic NMDA-receptors elicit opposing effects on nuclear morphology, [8]. The structural alterations of the cell nucleus have significant effects on nuclear calcium dynamics. Compartmentalization of the nucleus, due to membrane infoldings, changes calcium frequencies, amplitudes and spatial distributions, [8,10]. Since these parameters have been shown to control downstream events towards gene transcription, [11,12], the results elucidate the cellular control of nuclear function with the help of morphology modulation. With respect to processes downstream of calcium, we show that histone H3 phosphorylation is closely linked to nuclear morphology. Investigating the nuclear morphologies of hippocampal neurons, two major classes were identified [9,10]. One class contains non-infolded nuclei that have the function of calcium signal integrators, while the other class contains highly infolded nuclei, which function as frequency detectors of nuclear calcium, [10]. Extending this interdisciplinary approach of investigating structure/function relationships in neurons, the effects of cellular morphology – as well as the morphology of the endoplasmic reticulum and other organelles – on neuronal calcium signals is currently being investigated. This endeavor makes use of highly detailed, three-dimensional models of neuronal calcium dynamics, including the three-dimensional morphology of the cell and its organelles

Late Cretaceous marine transgressions in Ecuador and northern Peru: a refined stratigraphic framework.

Study of ammonites and bivalves along selected sections on the Andean margin of northern Peru and Ecuador has made it possible to recognize correlatable marine transgressions and to propose a refined stratigraphic framework for the Upper Cretaceous of the region. Six maximum flooding events are recognized: latest Turonian–early Coniacian (major event), late Coniacian–early Santonian, late Santonian–early Campanian, mid Campanian–early late Campanian (major event), early Maastrichtian (major event), and terminal early Maastrichtian. Most of these events can be correlated with global eustatic sea-level rises, but their relative manifestations indicate that the Andean margin was already being deformed by the late Cretaceous “Peruvian” tectonic events. The onset of fine-grained clastic sedimentation in the Oriente and East-Peruvian basins in the mid Turonian–earliest Coniacian is taken as the first event of the “Peruvian” phase. The Campanian regional transgression in the Peruvian-Ecuadorian forearc zones concealed the “Peruvian” deformational event. The latter caused a palaeogeographic upheaval, indicated by the subsequent development of a NNE-trending forearc basin, which extended from Paita in northwestern Peru to northern Ecuador. In the forearc zones only short-lived transgressions are recorded in the late Campanian and early Maastrichtian as a result of nearly continuous tectonic activity. This culminated with a significant tectonic event in the late Maastrichtian, causing a widespread hiatus

A quantitative method to assess extrasynaptic NMDA receptor function in the protective effect of synaptic activity against neurotoxicity

<p>Abstract</p> <p>Background</p> <p>Extrasynaptic NMDA receptors couple to a CREB shut-off pathway and cause cell death, whereas synaptic NMDA receptors and nuclear calcium signaling promote CREB-mediated transcription and neuronal survival. The distribution of NMDA receptors (synaptic versus extrasynaptic) may be an important parameter that determines the susceptibility of neurons to toxic insults. Changes in receptor surface expression towards more extrasynaptic NMDA receptors may lead to neurodegeneration, whereas a reduction of extrasynaptic NMDA receptors may render neurons more resistant to death. A quantitative assessment of extrasynaptic NMDA receptors in individual neurons is needed in order to investigate the role of NMDA receptor distribution in neuronal survival and death.</p> <p>Results</p> <p>Here we refined and verified a protocol previously used to isolate the effects of extrasynaptic NMDA receptors using the NMDA receptor open channel blocker, MK-801. Using this method we investigated the possibility that the known neuroprotective shield built up in hippocampal neurons after a period of action potential bursting and stimulation of synaptic NMDA receptors is due to signal-induced trafficking of extrasynaptic NMDA receptors or a reduction in extrasynaptic NMDA receptor function. We found that extrasynaptic NMDA receptor-mediated calcium responses and whole cell currents recorded under voltage clamp were surprisingly invariable and did not change even after prolonged (16 to 24 hours) periods of bursting and synaptic NMDA receptor activation. Averaging a large number of calcium imaging traces yielded a small (6%) reduction of extrasynaptic NMDA receptor-mediated responses in hippocampal neurons that were pretreated with prolonged bursting.</p> <p>Conclusion</p> <p>The slight reduction in extrasynaptic NMDA receptor function following action potential bursting and synaptic NMDA receptor stimulation could contribute to but is unlikely to fully account for activity-dependent neuroprotection. Other factors, in particular calcium signaling to the nucleus and the induction of survival promoting genes are more likely to mediate acquired neuroprotection.</p

Extrasynaptic NMDA Receptors : Mediators of Excitotoxic Cell Death

The N-methyl-D-aspartate (NMDA) type of glutamate receptor is a calcium-permeable ion channel with important functions in the physiology and pathology of the mammalian brain. NMDA receptors are critical for long-lasting, activity-induced changes in synaptic transmission, a process thought to be involved in learning and memory. NMDA receptors also control neuronal survival and cell death. How can the biological consequences of NMDA receptor activation be so diametrically opposed? The outcome of NMDA receptor activation appears to be determined by its localization. Stimulation of synaptic NMDA receptors (by synaptically-released glutamate) activates gene expression mediated by the transcription factor, cAMP-response element-binding-protein (CREB) and induces pro-survival events. In contrast, calcium flux through extrasynaptic NMDA receptors overrides these functions, shutting off CREB activity, and causing mitochondrial dysfunction and cell death. These differences in the biological response are likely due to differences in the intracellular signaling complexes associated with synaptic vs. extrasynaptic NMDA receptors. As extrasynaptic NMDA receptors are thought to be activated following hypoxic/ischemic insults, specific blockade of extrasynaptic NMDA receptors or its signaling complex may efficiently reduce neuron loss following stroke

Spatial and temporal variation in otolith chemistry for tautog (Tautoga onitis) in Narragansett Bay and Rhode Island coastal ponds

The elemental composition of otoliths may provide valuable information for establishing connectivity between fish nursery grounds and adult fish populations. Concentrations of Rb, Mg, Ca, Mn, Sr, Na, K, Sr, Pb, and Ba were determined by using solution-based inductively coupled plasma mass spectrometry in otoliths of young-of-the year tautog (Tautoga onitis) captured in nursery areas along the Rhode Island coast during two consecutive years. Stable oxygen (δ18O) and carbon (δ13C) isotopic ratios in young-of-the year otoliths were also analyzed with isotope ratio mass spectrometry. Chemical signatures differed significantly among the distinct nurseries within Narragansett Bay and the coastal ponds across years. Significant differences were also observed within nurseries from year to year. Classification accuracy to each of the five tautog nursery areas ranged from 85% to 92% across years. Because accurate classification of juvenile tautog nursery sites was achieved, otolith chemistry can potentially be used as a natural habitat tag

A transcription-dependent increase in miniature EPSC frequency accompanies late-phase plasticity in cultured hippocampal neurons

<p>Abstract</p> <p>Background</p> <p>The magnitude and longevity of synaptic activity-induced changes in synaptic efficacy is quantified by measuring evoked responses whose potentiation requires gene transcription to persist for more than 2-3 hours. While miniature EPSCs (mEPSCs) are also increased in amplitude and/or frequency during long-term potentiation (LTP), it is not known how long such changes persist or whether gene transcription is required.</p> <p>Results</p> <p>We use whole-cell patch clamp recordings from dissociated hippocampal cultures to characterise for the first time the persistence and transcription dependency of mEPSC upregulation during synaptic potentiation. The persistence of recurrent action potential bursting in these cultures is transcription-, translation- and NMDA receptor-dependent thus providing an accessible model for long-lasting plasticity. Blockade of GABA_A-receptors with bicuculline for 15 minutes induced action potential bursting in all neurons and was maintained in 50-60% of neurons for more than 6 hours. Throughout this period, the frequency but neither the amplitude of mEPSCs nor whole-cell AMPA currents was markedly increased. The transcription blocker actinomycin D abrogated, within 2 hours of burst induction, both action potential bursting and the increase in mEPSCs. Reversible blockade of action potentials during, but not after this 2 hour transcription period suppressed the increase in mEPSC frequency and the recovery of burst activity at a time point 6 hours after induction.</p> <p>Conclusion</p> <p>These results indicate that increased mEPSC frequency persists well beyond the 2 hour transcription-independent phase of plasticity in this model. This long-lasting mEPSC upregulation is transcription-dependent and requires ongoing action potential activity during the initial 2 hour period but not thereafter. Thus mEPSC upregulation may underlie the long term, transcription-dependent persistence of action potential bursting. This provides mechanistic insight to link gene candidates already identified by gene chip analysis to long lasting plasticity in this in vitro model.</p

The Abundance of Harbor Seals in the Gulf of Alaska

The abundance of harbor seals (Phoca vitulina richardii) has declined in recent decades at several Alaska locations. The causes of these declines are unknown, but there is concern about the status of the populations, especially in the Gulf of Alaska. To assess the status of harbor seals in the Gulf of Alaska, we conducted aerial surveys of seals on their haul-out sites in August-September 1996. Many factors influence the propensity of seals to haul out, including tides, weather, time of day, and time of year. Because these “covariates” cannot simultaneously be controlled through survey design, we used a regression model to adjust the counts to an estimate of the number of seals that would have been ashore during a hypothetical survey conducted under ideal conditions for hauling out. The regression, a generalized additive model, not only provided an adjustment for the covariates, but also confirmed the nature and shape of the covariate effects on haul-out behavior. The number of seals hauled out was greatest at the beginning of the surveys (mid-August). There was a broad daily peak from about 1100-1400 local solar time. The greatest numbers were hauled out at low tide on terrestrial sites. Tidal state made little difference in the numbers hauled out on glacial ice, where the area available to seals did not fluctuate with the tide. Adjusting the survey counts to the ideal state for each covariate produced an estimate of 30,035 seals, about 1.8 times the total of the unadjusted counts (16,355 seals). To the adjusted count, we applied a correction factor of 1.198 from a separate study of two haul-out sites elsewhere in Alaska, to produce a total abundance estimate of 35,981 (SE 1,833). This estimate accounts both for the effect of covariates on survey counts and for the proportion of seals that remained in the water even under ideal conditions for hauling out

The Abundance of Harbor Seals in the Gulf of Alaska

The abundance of harbor seals (Phoca vitulina richardii) has declined in recent decades at several Alaska locations. The causes of these declines are unknown, but there is concern about the status of the populations, especially in the Gulf of Alaska. To assess the status of harbor seals in the Gulf of Alaska, we conducted aerial surveys of seals on their haul-out sites in August-September 1996. Many factors influence the propensity of seals to haul out, including tides, weather, time of day, and time of year. Because these “covariates” cannot simultaneously be controlled through survey design, we used a regression model to adjust the counts to an estimate of the number of seals that would have been ashore during a hypothetical survey conducted under ideal conditions for hauling out. The regression, a generalized additive model, not only provided an adjustment for the covariates, but also confirmed the nature and shape of the covariate effects on haul-out behavior. The number of seals hauled out was greatest at the beginning of the surveys (mid-August). There was a broad daily peak from about 1100-1400 local solar time. The greatest numbers were hauled out at low tide on terrestrial sites. Tidal state made little difference in the numbers hauled out on glacial ice, where the area available to seals did not fluctuate with the tide. Adjusting the survey counts to the ideal state for each covariate produced an estimate of 30,035 seals, about 1.8 times the total of the unadjusted counts (16,355 seals). To the adjusted count, we applied a correction factor of 1.198 from a separate study of two haul-out sites elsewhere in Alaska, to produce a total abundance estimate of 35,981 (SE 1,833). This estimate accounts both for the effect of covariates on survey counts and for the proportion of seals that remained in the water even under ideal conditions for hauling out

Sedimentary record of terminal Cretaceous accretions in Ecuador: the Yunguilla Group in the Cuenca area

15 pages Sous presse dans le: "Journal of South American Earth Sciences"A reappraisal of the “Late Cretaceous Yunguilla Formation” of the Cuenca area made it possible to define four distinct formations, correlatable with those of southwestern Ecuador. A mid to late Campanian marine transgression (Jadán Fm) is overlain by quartz-rich conglomerates of fan-delta to turbiditic fan environment (Quimas Fm) of latest Campanian-earliest Maastrichtian age, which are interpreted as evidence of the accretion of a first oceanic terrane (San Juan). Disconformable, arkosic turbidites and cherts (Tabacay Fm) of early Maastrichtian age are thought to represent the erosion of the newly accreted oceanic terrane. A major unconformity of late Maastrichtian age, caused by the accretion of a second oceanic terrane (Guaranda), is followed by the deposition of quartz-rich micaceous shelf sandstones (Saquisilí Fm) of Paleocene age. A third accretion event (late Paleocene) is recorded in coastal Ecuador. Each accretion event correlates with the uplift and erosion of the Eastern Cordillera, and with a sedimentary hiatus in the eastern areas. This suggests that in Ecuador, accretion of oceanic terranes contributed to the build-up of the Andes through tectonic underplating of low-density material, and that the eastern areas did not behave as a flexural foreland basins during late Cretaceous-Paleogene times