Understanding calcium waves and sparks in central neurons

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Reviews Neuroscience 13 (2012): 157-168, doi:10.1038/nrn3168.All cells use changes in intracellular calcium concentration [Ca2+]i to regulate cell signaling events In neurons, with their elaborate dendritic and axonal arborizations, there are clear examples of both localized and widespread Ca2+ signals. [Ca2+]i changes generated by Ca2+ entry through voltage gated and ligand gated channels are the best characterised. In addition, [Ca2+]i can increase by release from intracellular stores. These signals have been less studied, in part because they usually are not associated with specific changes in membrane potential. However, recent experiments have revealed dramatic widespread Ca2+ waves and localized spark-like events, particularly in dendrites. Here we review emerging data on the nature of these signals and their functions.Supported by a grant from the National Institutes of Health (NS-16295).2012-08-0

High Water Marks

Incentive fees for money managers are frequently accompanied by high-water mark provisions that condition the payment of the performance fee upon exceeding the previously achieved maximum share value. In this paper, we show that hedge fund performance fees are valuable to money managers, and conversely, represent a claim on a significant proportion of investor wealth. The high-water mark provisions in these contracts limit the value of the performance fees. We provide a closed-form solution to the cost of the high-water mark contract under certain conditions. Our results provide a framework for valuation of a hedge fund management company.

Sodium dynamics in pyramidal neuron dendritic spines : synaptically evoked entry predominantly through AMPA receptors and removal by diffusion

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Neuroscience 37 (2017): 9964-9976, doi:10.1523/JNEUROSCI.1758-17.2017.Dendritic spines are key elements underlying synaptic integration and cellular plasticity, but many features of these important structures are not known or are controversial. We examined these properties using newly developed simultaneous sodium and calcium imaging with single-spine resolution in pyramidal neurons in rat hippocampal slices from either sex. Indicators for both ions were loaded through the somatic patch pipette, which also recorded electrical responses. Fluorescence changes were detected with a high-speed, low-noise CCD camera. Following subthreshold electrical stimulation, postsynaptic sodium entry is almost entirely through AMPA receptors with little contribution from entry through NMDA receptors or voltage-gated sodium channels. Sodium removal from the spine head is through rapid diffusion out to the dendrite through the spine neck with a half-removal time of ∼16 ms, which suggests the neck has low resistance. Peak [Na+]i changes during single EPSPs are ∼5 mm. Stronger electrical stimulation evoked small plateau potentials that had significant longer-lasting localized [Na+]i increases mediated through NMDA receptors.This work was supported in part by National Institutes of Health Grants R21NS085729 and R01NS099122.2018-03-1

Ca2+ sparks and puffs are generated and interact in rat hippocampal CA1 pyramidal neuron dendrites

Author Posting. © The Authors, 2013. This article is posted here by permission of Society for Neuroscience for personal use, not for redistribution. The definitive version was published in Journal of Neuroscience 33 (2013): 17777-17788, doi: 10.1523/JNEUROSCI.2735-13.2013.1,4,5-Inositol trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) mediate release of Ca2+ from internal stores in many neurons. The details of the spatial and temporal characteristics of these signals and their interactions in dendrites remain to be clarified. We found that localized Ca2+ release events, with no associated change in membrane potential, occurred spontaneously in the dendrites of rat hippocampal CA1 pyramidal neurons. Their rate, but not their amplitude or time course, could be modulated by changes in membrane potential. Together, these results suggest that the spontaneous events are similar to RyR-dependent Ca2+ “sparks” found in cardiac myocytes. In addition, we found that we could generate another kind of localized Ca2+ release event by either a synaptic tetanus in the presence of 3-((R)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid and CNQX or by uncaging IP3. These events had slower rise times and decay times than sparks and were more heterogeneous. These properties are similar to Ca2+ “puffs” found in oocytes. These two localized signals interact. Low-intensity tetanic synaptic stimulation or uncaging of IP3 increased the decay time of spontaneous Ca2+ events without changing their rise time or amplitude. Pharmacological experiments suggest that this event widening is attributable to a delayed IP3R-mediated release of Ca2+ triggered by the synergistic action of IP3 and Ca2+ released by RyRs. The actions of IP3 appear to be confined to the main apical dendrite because uncaging IP3 in the oblique dendrites has no effect on the time course of localized events or backpropagating action potential-evoked Ca2+ signals in this region.This work was supported in part by National Institutes of Health Grant NS016295.2014-05-0

Simultaneous sodium and calcium imaging from dendrites and axons

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in eNeuro 2 (2015): ENEURO.0092-15.2015, doi:10.1523/ENEURO.0092-15.2015.Dynamic calcium imaging is a major technique of neuroscientists. It can reveal information about the location of various calcium channels and calcium permeable receptors, the time course, magnitude, and location of intracellular calcium concentration ([Ca2+]i) changes, and indirectly, the occurrence of action potentials. Dynamic sodium imaging, a less exploited technique, can reveal analogous information related to sodium signaling. In some cases, like the examination of AMPA and NMDA receptor signaling, measurements of both [Ca2+]i and [Na+]i changes in the same preparation may provide more information than separate measurements. To this end, we developed a technique to simultaneously measure both signals at high speed and sufficient sensitivity to detect localized physiologic events. This approach has advantages over sequential imaging because the preparation may not respond identically in different trials. We designed custom dichroic and emission filters to allow the separate detection of the fluorescence of sodium and calcium indicators loaded together into a single neuron in a brain slice from the hippocampus of Sprague-Dawley rats. We then used high-intensity light emitting diodes (LEDs) to alternately excite the two indicators at the appropriate wavelengths. These pulses were synchronized with the frames of a CCD camera running at 500 Hz. Software then separated the data streams to provide independent sodium and calcium signals. With this system we could detect [Ca2+]i and [Na+]i changes from single action potentials in axons and synaptically evoked signals in dendrites, both with submicron resolution and a good signal-to-noise ratio (S/N).This work was supported by NIH grant R21 NS085729 and the New York Medical College Intramural Research Support Program

Sodium Dynamics in Pyramidal Neuron Dendritic Spines: Synaptically Evoked Entry Predominantly Through AMPA Receptors and Removal by Diffusion

Dendritic spines are key elements underlying synaptic integration and cellular plasticity, but many features of these important structures are not known or are controversial. We examined these properties with newly developed simultaneous sodium and calcium imaging that had single spine resolution in pyramidal neurons in rat hippocampal slices from either sex. Indicators for both ions were loaded through the somatic patch pipette, which also recorded electrical responses. Fluorescence changes were detected with a high speed, low noise CCD camera. Following subthreshold electrical stimulation postsynaptic sodium entry is almost entirely through AMPA receptors with little contribution from entry through NMDA receptors or voltage gated sodium channels. Sodium removal from the spine head is through rapid diffusion out to the dendrite through the spine neck with a half removal time of about 16 ms, which suggests the neck has low resistance. Peak [Na+]i changes during single EPSPs are about 5 mM. Stronger electrical stimulation evoked small plateau potentials that had significant longer lasting localized [Na+]i increases mediated through NMDA receptors.SIGNIFICANCE STATEMENTDendritic spines are small structures that are difficult to investigate, but are important elements in the fundamental processes of synaptic integration and plasticity. Although calcium imaging has been the main tool for examining these structures there are limits to the kinds of information it reveals. We used newly developed, high speed, simultaneous sodium and calcium imaging to examine ion dynamics in spines in hippocampal pyramidal neurons. We found that following single subthreshold synaptic activation most sodium entry was through AMPA receptors and not through NMDA receptors or voltage gated sodium channels and that the spine neck is not a significant resistance barrier. Most spine mechanisms are linear. However, regenerative NMDA conductances can be activated with stronger stimulation

Synaptically activated Ca2+ waves and NMDA spikes locally suppress voltage-dependent Ca2+ signalling in rat pyramidal cell dendrites

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of The Physiological Society for personal use, not for redistribution. The definitive version was published in Journal of Physiology 589 (2011): 4903-4920, doi:10.1113/jphysiol.2011.216564.Synaptically activated changes in dendritic [Ca2+]i affect many important physiological processes including synaptic plasticity and gene expression. The location, magnitude, and time course of these changes can determine which mechanisms are affected. Therefore, it is important to understand the processes that control and modulate these changes. One important source is Ca2+ entering through voltage gated Ca2+ channels opened by action potentials backpropagating over the dendrites (bAPs). Here we examine how [Ca2+]i changes, caused by regenerative Ca2+ release from internal stores (Ca2+ waves) or by regenerative Ca2+ entry through NMDA receptors (NMDA spikes) affect subsequent bAP evoked [Ca2+]i changes. These large [Ca2+]i increases suppressed the bAP signals in the regions where the preceding [Ca2+]i increases were largest. The suppression was proportional to the magnitude of the large [Ca2+]i change and was insensitive to kinase and phosphatase inhibitors, consistent with suppression due to Ca2+ dependent inhibition of Ca2+ channels.Supported in part by NIH grant NS-016295.2012-08-1

Evaluating susceptibility of red-cockaded woodpecker cavity trees to southern pine beetle in Texas

Characteristics of loblolly (Pinus fuedu L.) and shortleaf (Pinus echinutu Mill.) pine trees favored by the endangered red-cockaded woodpecker, Picuides borealis (Vieillot) for nesting and roosting cavities over much of eastern Texas, tend to make these trees highly vulnerable to mortality from bark beetle attack. Resin flow and xylem moisture potential, often used as indicators of pine susceptibility to bark beetle mortality, were measured in several red-cockaded woodpecker cavity tree clusters in the Angelina and Davy Crockett National Forests. No differences in xylem moisture potential were found, while resin flow varied by site, tree species, and cavity tree type. With over half of cavity tree mortality in Texas caused by southern pine beetle, Dendroctonusfrontalis Zimmerman, pro-active management to reduce bark beetle hazard in southern pine stands is imperative

Improvements in simultaneous sodium and calcium imaging

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Frontiers in Cellular Neuroscience 12 (2019): 514. doi: 10.3389/fncel.2018.00514.High speed imaging of ion concentration changes in neurons is an important and growing tool for neuroscientists. We previously developed a system for simultaneously measuring sodium and calcium changes in small compartments in neurons (Miyazaki and Ross, 2015). We used this technique to analyze the dynamics of these ions in individual pyramidal neuron dendritic spines (Miyazaki and Ross, 2017). This system is based on high speed multiplexing of light emitting diodes (LEDs) and classic organic indicators. To improve this system we made additional changes, primarily incorporating lasers in addition to the LEDs, more sophisticated imaging protocols, and the use of newer sodium and calcium indicators. This new system generates signals with higher signal to noise ratio (S/N), less background fluorescence, and less photodynamic damage. In addition, by using longer wavelength indicators instead of indicators sensitive in the UV range, it allows for the incorporation of focal uncaging along with simultaneous imaging, which should extend the range of experiments.This work was supported in part by National Institutes of Health Grants R21NS085729 (WR), R01NS099122 (WR), and R01NS103168 (JL)