1985 |
Meredith, Gloria E. |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Mechanisms of Central Auditory Processing @ University of Amsterdam |
0.916 |
1986 — 1987 |
Meredith, Gloria E. |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Mechanisms of Efferent Activation in the Auditory System @ University of Amsterdam |
0.916 |
2001 — 2004 |
Meredith, Gloria E. |
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. |
Synaptic Proteins, Trophic Factors and Neurodegeneration @ Rosalind Franklin Univ of Medicine &Sci
Description (Provided by applicant): One of the most fundamental questions related to the progressive nature of neurodegeneration in human disease is how neurons die. Protecting nerve cells against morphological decline and death requires blocking intrinsic factors that inhibit neural repair. In the present proposal, we offer an innovative approach to study those factors that are active in Parkinson's disease (PD) in a new mouse model that shows synaptic loss and irreversible nigrostriatal degeneration. We propose to track changes of a key synaptic protein, a-synuclein, both in its native environment at presynaptic terminals and under neurotoxic conditions, when it becomes insoluble and accumulates. We will further correlate those changes with altered neurotrophic support. We have established an animal protocol by treating C57/bl mice with a combined regimen of 10 doses of probenecid at 250mg/kg and MPTP at 25mg/kg for 5 weeks. These mice show a slow, progressive loss of nigrostriatal dopaminergic function for at least 6 months, that mimics PD, with no signs of recovery. Three weeks after drug treatment, there is a significant reduction in the number of substantia nigra (SN) cells and dramatic changes in the subsynaptic distribution and density of a-synuclein-immunoreactive terminals. These changes could signal the beginning of a chain of events that leads to cell death. In this proposal, we will focus on the progressive deterioration of dopaminergic neurons in the SN and their inputs, and present three specific aims to be addressed through a series of hypotheses. Specifically, we plan to 1) ascertain the origin and neurochemical phenotype of synapses in the SN that contain a-synuclein and to establish whether MPTP + probenecid treatment leads to their degeneration; 2) determine, in the MPTP+P model, the temporal relationships between cell death and a-synuclein-positive synapses, decline in dopamine function and behavior; and 3) ascertain whether changes in a-synuclein expression and production are precipitated by altered neurotrophic support. The overall objective of our research is to understand the relationship between the synaptic protein, a-synuclein, neurotrophic support, especially brain-derived neurotrophic factor (BDNF) and their respective roles in the PD form of neurodegeneration. The findings of this research should shed light on target areas where neuroprotection strategies can be implemented.
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0.938 |
2003 — 2010 |
Meredith, Gloria E. |
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. |
Mechanisms Underlying Reward-Related Synaptogenesis @ Rosalind Franklin Univ of Medicine &Sci
When amphetamine is repeatedly associated with the same environmental context, the environment becomes a powerful stimulus to elicit memories of the drug experience. These memories bring out a strong, physiological response, even in the absence of drug. Such associative learning is maladaptive and contributes to the poor judgment of individuals who crave the drug. However, we know surprisingly little of the synaptic modifications that shape drug-related memories, even though memory retrieval appears critical for the persistence of drug-seeking behavior. Conditioned place preference (CPP) is a model of cue-elicited drug seeking. When amphetamine is repeatedly paired with the same environment, rats learn to associate the rewarding effects of the drug with the cues provided by the environment. Our work has shown that the neural circuitry underlying this behavior could involve synaptic interactions between the hippocampal formation and basolateral amygdala (BLA). We have shown that amphetamine-induced CPP (AM PH CPP) is accompanied by increased synapses and a significant elevation in synaptic drive from the hippocampal formation. We believe that drug-seeking behavior therefore requires both structural and functional plasticity of BLA pyramidal cells to consolidate the learned association of drug and environment. We hypothesize further that this plasticity is mediated by the hippocampal formation. Through experiments outlined herein, we have set 2 specific aims: (1) The first will determine how AMPH CPP rewires BLA pyramidal neurons. The goal is to examine how CPP alters the eXCitatory and inhibitory synaptic complements of pyramidal neurons, using light and electron microscopy, immunocytochemistry and stereology. (2) In the scond, we will determine if AM PH CPP causes enhanced eXCitatory synaptic drive of BLA pyramidal neurons. The goals are to determine, using in vivo intracellular electrophysiological recordings, if BLA pyramidal neurons are subjected to abnormal excitatory drive, and if the hippocampal formation contributes to the excitation. The neuronal structure (dendrites and spines) of recorded BLA neurons will be studied to establish whether morphogenesis (increased spines, dendritic length and branching) is indicative of the strong increases in synaptic drive.
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0.938 |
2015 — 2018 |
Jin, Sha Rozners, Eriks (co-PI) [⬀] Ye, Kaiming [⬀] Meredith, Gloria |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Mri: Acquisition of a Multiphoton Confocal Laser Scanning Microscope For Life Science and Biomedical Research and Training At Suny Binghamton
This proposal seeks to acquire a Zeiss LSM 880 NOL 3-channel multiphoton confocal laser scanning microscope to upgrade SUNY Binghamton University's (BU) eight-year-old Leica SP 5 single photon confocal microscope that has helped BU faculty to successfully develop top-ranked research programs. The existing microscope was originally configured for thin tissue sample and microorganism imaging. With the expansion of BU research programs in neuroscience, stem cell and regenerative medicine, 3D tissue bioprinting, nanomedicine, etc., the University is in urgent need of a more advanced multiphoton confocal microscope for live cell imaging. LSM880 NOL is a two photon confocal microscope capable of subcellular imaging. Access to this state-of-the-art microscope will propel BU's recent Health Science Initiative, boost faculty research capabilities in Biomedical Engineering, Biological Science, Chemistry, and Psychology Departments and the newly-formed Pharmacy School. It will also help more individuals on campus obtain preliminary results to seek for NSF and NIH funding. The outcome of this project would have a broader impact on our fundamental understanding of how cell and protein behave dynamically in vivo. This project address unmet needs to study cell biology, gene regulation, neuron firing, and tissue regeneration/remodeling in live cells, tissues, and small animals at single cell and single molecule level. Furthermore, its acquisition will foster BU's collaboration with industries to accelerate the translation of life science and biomedical engineering discoveries into bioproducts. A comprehensive management plan will ensure that the instrument always runs at peak and near peak capacity. The strong financial and management commitment from BU and the researchers involved in this project will sustain the facility after the project period.
This proposal seeks to acquire a Zeiss LSM 880 NOL 3-channel multiphoton confocal laser scanning microscope to upgrade SUNY Binghamton University's (BU) eight-year-old Leica SP 5 single photon confocal microscope that has helped BU faculty to successfully develop top-ranked research programs. LSM880 NOL is a two photon confocal microscope. Its pulsed, ultrafast infrared laser excites fluorescent dyes or proteins only at the focal point, where photon density is high enough to produce fluorescence. The red excitation light penetrates much deeper into tissue close to 1 mm. It can resolve 140 nm laterally and 400 nm axially at 488 nm, allowing for subcellular imaging. The breadth of research interests, coupled with the current funding of investigators involved in this project poses urgent need for the acquisition of the microscope at BU. The acquisition of this advanced multiphoton microscope will immediately affect more than 17 research labs across six Departments in three schools. More labs will be impacted once the system is set up on campus. The investigators involved in this project are well funded by NSF, NIH, etc. and have research projects that are directly related to the microscope. The acquisition of the instrument will not only permit them to develop more collaborative projects with researchers across the campus, state and nation, but it will also allow faculty to pursue new directions of research and contribute greatly to the growth of BU's research and academic programs. It will enable investigators to study interaction between cell-cell and cell-extracellular matrix; to track cell migration, differentiation, and proliferation; to investigate cell recruitment during wound healing, organ transplantation and tissue regeneration/remodeling; and to measure biochemical reactions such as diffusion, receptors/ligand interaction within live cells, tissues, 3D printed organoids or small animals. Knowledge gained from these studies will significantly advance both bioscience and bioengineering. The acquisition of the microscope will propel and accelerate these advances. It will remarkably enhance BU's research infrastructure in life science and biomedical engineering by providing a multiuser imaging facility that is open to all investigators and students across the campus, state, and nation. Furthermore, it will provide a powerful resource for teaching modern biology and bioengineering. A new lab course focusing on live cell and tissue multiphoton microscopy will be developed and offer to both undergraduate and graduate students. Workshops and open house will be held to train and attract new users to access to the microscope and to reach out to K-12 and local communities, especially those from underrepresented groups. It will offer additional research training opportunities for summer REU students. Finally, it will serve as an excellent recruiting tool for attracting top-notch faculty to the university.
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0.901 |