1986 |
Ross, William Noel |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Analysis of Graded Visual Signals @ New York Medical College
We will study synaptic integration, regional membrane properties, and control of internal calcium in neurons of the supraesophageal ganglion of the giant barnacle Balanus nubilus. We are particularly, but not exclusively, interested in these properties in neurons in the visual pathway where information is processed and transmitted by graded potentials and not action potentials. The barnacle ganglion has several advantageous morphological and physiological features for studying these properties. Most of these events occur on the dendrites or presynaptic terminals of cells and hence cannot be easily examined using microelectrodes. We will employ optical methods using voltage-senstive dyes to record simultaneously from many positions on individual cells, including fine processes. With this technique we will determine passive membrane properties at many positions on the cell, regional variations in ionic conductance mechanisms, synapse locations and the propagation of synaptic potentials within a cell. For some selected neurons, we will attempt to combine all of these properties into a unified electrical model. In addition, we will examine the control of internal calcium in the presynaptic terminal of the median photoreceptor. This is an example of a non-fatiguing, graded synapse. With the same apparatus used for the membrane potential measurements we will measure changes in absorption in the dye Arsenazo III to indicate changes in internal calcium at different positions and under a variety of physiological conditions in the photoreceptor.
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1987 — 1991 |
Ross, William Noel |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Optical Analysis of the Regional Properties of Neurons @ New York Medical College
We will study synaptic integration, regional membrane properties, and control of internal calcium in neurons of the supraesophageal ganglion of the giant barnacle, Balanus nubilus and the stomatogastric ganglion of the crab, Cancer borealis. Many of the interesting aspects of these problems occur on the dendrites or presynaptic terminals of these cells and therefore cannot be easily examined with microelectrodes. Therefore we will employ optical methods which we have been developing to examine these previously inaccessible regions. Using both voltage sensitive dyes and calcium indicator dyes we will map the spread of electrical potentials and properties of calcium transients simultaneously throughout these neurons. From these measurements we will determine the passive membrane properties at many locations, regional variations in ionic conductance mechanisms, synapse locations and the propagation of synaptic and action potentials in the cell. In addition, the threshold and time course of calcium transients will be examined to reveal regional variations in the properties of calcium channels and calcium buffering mechanisms. Both the techniques we develop and the conclusions we reach should be of general value in understanding cellular and synaptic mechanisms in a wide variety of preparations, from single neurons in culture to neurons in the mammalian brain.
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1989 — 1999 |
Ross, William Lasser-Ross, Nechama |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Optical Analysis of Synaptic Integration in Cerebellar Purkinje Cells @ New York Medical College
9514266 Ross The central nervous system often appears like a dense, bewildering array of neurons and of neuronal synaptic interactions. Part of the problem is that the functional significance of specific locations at which synapses occur on cells is largely unknown. The focus of research funded by this grant is on determining the significance of the spatial arrangement of synapses on Purkinje cells, which are the largest neurons in the cerebellum and which provide the only output to other parts of the brain. This focus relates to the complex problem of how voltage-dependent membrane conductances in Purkinje cell input regions, the dendrites, and the architecture of these neurons influence the integration process. Experiments are designed to determine the functional significance of the spatial patterns of these synaptic inputs. The primary technique is optical recording of calcium concentrations through the use of indicator dyes in slices of brain tissue. Calcium concentrations, when combined with an electrical recording, are good indicators of changes in intracellular potentials throughout neurons and hence of local neuronal activity. The relatively stereotyped circuitry of the cerebellar cortex provides a favorable model system for studying the functional significance of cell geometry and synaptic interactions in detail. These studies should provide much needed, detailed descriptions of synaptic interactions in critically important cerebellar neurons. Such descriptions will greatly enhance knowledge of information processing in mammalian neurons at the single cell level.
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0.915 |
1993 |
Ross, William Noel |
F06Activity Code Description: Undocumented code - click on the grant title for more information. |
Analysis of Active Properties of Cns Dendrites @ New York Medical College |
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1994 — 2003 |
Ross, William Noel |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Calcium and Integration in Pyramidal Cells @ New York Medical College
DESCRIPTION: (Applicant's Abstract) The long-term goal of this project is to contribute to the understanding of dendritic mechanisms underlying synaptic integration and plasticity. These fundamental cellular processes play an important role in the more global mechanisms of information processing, learning and memory. In the current proposal, we are focusing our attention on neurons in the CA1 region of the rat hippocampus, studied in the brain slice preparation. We are interested in how neuromodulators, normally released from diffuse fibers in the hippocampus, affect spike propagation and associated [Ca2+]i changes in the dendrites of pyramidal neurons. We will analyze the modulation of [Ca2+]i changes due to changes in the voltage profile of the spikes, modulation of dendritic Ca2+ channels, and control of the release of Ca2+ from internal stores. We also will analyze spike propagation and [Ca2+]i changes in interneurons. We will analyze these problems using a combination of high-speed fluorescence imaging of individual neurons filled with Ca2+-sensitive indicators, and whole-cell recording from cell bodies and dendrites. The electrical recordings directly reveal information about spike propagation at the site of recording. The imaging data give a more global picture of spike propagation in different parts of the neuron as well as directly revealing information about activity-dependent [Ca2+]i changes.
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2004 — 2011 |
Ross, William Noel |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
Calcium Waves in Pyramidal Neurons @ New York Medical College
DESCRIPTION (provided by applicant): Postsynaptic [Ca2+]i changes in pyramidal neurons in the hippocampus play an important role in the induction of various forms of synaptic plasticity, gene expression, and modulation of membrane conductances. All of these mechanisms can affect the behavior of these neurons in circuits involved in learning and memory. Therefore, a detailed understanding of these processes is important for understanding brain function. There are three clear sources of Ca2+ in pyramidal neurons that can be activated by synaptic mechanisms in the hippocampus: Ca2+ entry through NMDA receptors, entry through voltage-dependent Ca2+ channels, and Ca2+ release from internal stores. We will investigate the properties and functions of Ca2+ released from stores mediated by activation of IP3 receptors and ryanodine receptors in pyramidal cells in slices from the CA1 region of the hippocampus in Sprague Dawley rats. The first set of experiments will examine the properties of newly discovered spontaneous elementary events in the main dendrites of these neurons. These local events can be modulated by membrane potential and mGluR mediated synaptic transmission and could have important signaling functions by themselves. The second set of experiments will examine the properties of these events in the oblique dendrites, soma, and axon. Previous experiments established that Ca2+ release waves, which are probably built from these events, are not found in these regions. We will try to understand the restricted spatial distribution of waves and more widespread distribution of elementary events. The location and time course of these events will be examined with high speed imaging and 2-photon microscopy. Stimulation with synaptic transmission will be supplemented with focal uncaging of extracellular glutamate and carbachol and intracellular IP3 and Ca2+ to achieve precise localization of signaling events in thick or thin dendritic regions. We will investigate the function of Ca2+ released from stores in several important physiological processes, with particular emphasis on the different consequences of Ca2+ released in different dendritic regions. One set of experiments will examine the role of Ca2+ release in the induction of plasticity of cell excitability. A second set of experiments will examine the role of the Ca2+ waves in suppressing synaptic inhibition onto pyramidal neurons mediated by endogenous cannabinoids. PUBLIC HEALTH RELEVANCE: This project will examine the properties and function of synaptically activated calcium release from internal stores in pyramidal neurons. Information about this source of calcium could be relevant for understanding plastic changes in brain circuits and therefore important for understanding the cellular mechanisms underlying learning and memory. Defects in these processes have been implicated in several pathological conditions including Alzheimer's disease, schizophrenia and depression.
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2014 — 2015 |
Ross, William Noel |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Sodium Imaging of Synaptic Function @ New York Medical College
DESCRIPTION (provided by applicant): There has been a revolution in optical methods that now make it possible to peer into the brain and monitor its function. However, optical methods for measuring the strength of individual synapses have been lacking. The availability of such a method would revolutionize our ability to monitor single synapses and make it possible, by optical methods, to detect and monitor the changes in synaptic strength that underlie learning and memory. We propose to adapt modern technologies to improve methods for imaging [Na+]i changes in small neuronal compartments like dendritic spines. These improvements will include using LED light sources and fast CCD cameras to improve the detection of small rapid fluorescence changes and the use of a new generation of more sensitive sodium indicator dyes. We will also use several techniques to separate spine signals from dendrite signals without the need for a 2- photon microscope system. These spine localized sodium fluorescence signals can be interpreted as reflecting synaptically activated Na+ currents. Measuring these currents will reveal information about the receptor types involved in synaptic signaling at individual synaptic sites. We will also measure how these signals change following stimulation protocols related to synaptic plasticity.
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2016 — 2019 |
Ross, William Noel |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Combined Sodium and Calcium Imaging of Dendritic Function @ New York Medical College
Abstract Synaptic integration and calcium signaling are two of the most fundamental functions of neurons. Although models emphasizing the passive spread of potentials dominated early thinking we now know that there are many channel types and signaling molecules distributed over the dendritic arborization that contribute to the amplification of potentials and the activation of regenerative events in different dendritic regions and under different conditions. Exactly how these events are generated and interact is incompletely understood. Several postsynaptic mechanisms appear to particularly important since they are localized in specific dendritic regions and generate large calcium concentration changes. These include NMDA spikes, calcium waves, and localized spine calcium signals. We will use a recently developed a method to simultaneously image sodium and calcium changes in dendrites with high sensitivity and good spatial and temporal resolution. With this technique, combined with classic hippocampal slice electrophysiology and focal glutamate uncaging we will examine the properties of these events. We will explore the heterogeneous generation and propagation of NMDA spikes and calcium release events, determining their spatial boundaries and how they interact to synergistically amplify potentials and generate calcium signals. We will extend these measurements to an examination of some properties of dendritic spines, including the role of voltage dependent sodium channels, spine neck resistance, and the relative contribution of AMPA and NMDA receptor channels on individual spines. Knowledge of these properties is important for both an understanding of basic brain function and for elucidation of how their dysfunction might impact disease processes.
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