2007 — 2011 |
Jin, Xiaoming |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Excitatory and Inhibitory Synaptic Connectivity in Posttraumatic Epileptogenesis @ Indiana Univ-Purdue Univ At Indianapolis
Trauniatic brain injury often results in epilepsy that is poorly controlled by antiepileptic drugs. Although there is evitjence that axonal sproutingvenhanced excitatory synaptic connectivity and reduced inhibitory synaptic tranismisision are associated with posttraurriatic epileptogenesis, further information on how these changes occur and contribute to epileptogenesis is inconriplete. This information is crut^ial in providing a rational basis for the development of new therapies aimed to disrupt posttraumatic epileptogenesis. in the jai-pposed;study, I will use the partial cortical isolation ("undercut") niodel and,a novel prganotypic slice culture model of posttraumatic epileptogenesis to investigate alterations in excitatory and inhibitory synaptic connectivity, Three specific questions will be addressed: (1) Does axonal sprouting play a critical role in posttraumatic epileptogienesis? (2) is there an incfeaise in excitatory synaptic coupling;between layer V pyramidal neurons after a chronic partial cortical isolation? I will use a combination of single and paired vvhole ceil recording, laser scanning photostimulation (LSP), transgenic mice, organotypic brain slice culture, gene gun transfectibn, and time-lapse confocal microscopy techniques. An LSP-guided dual whole cell recording tiechiiit^ue will be developed to improve efficiency of paired recordings. The resiilts of these experiments will identify and characterize alterations in excitatory synaptic transmission in the epileptogenic neocortex, document morphological dynamics during axonal sprouting after traumatic brain injury, and establish a novel in vitro model of posttraumatic epileptogenesis. Results from the pi'bposed study will contribute to a further understanding of normal synaptic circuitry and pathological ciianges involved in posttraumatic epilepsy and provide insights for- development of noveltherapies for preventing epileptogenesis after brain trauma.
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1 |
2014 — 2017 |
Jin, Xiaoming |
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. |
Homeostatic Plasticity in the Control of Neuropathic Pain @ Indiana Univ-Purdue Univ At Indianapolis
DESCRIPTION (provided by applicant): Neuropathic pain (NP) is caused by a primary lesion of the nociceptive pathway. Hyperexcitability of this pathway resulting from peripheral and central sensitization is believed to be the neurophysiological hallmark of NP. Correspondingly, the standard paradigm of pharmacological management of NP is to suppress this hyperexcitability, as exemplified by the clinical use of certain antiepileptic drugs for the treatment of NP. However, the frequent refractoriness of NP to these drugs suggests that neuronal hyperexcitability should be approached differently. Because the pathophysiological process in NP exhibits a transition from an initial loss of afferent input to subsequent hyperexcitability and eventual paroxysmal discharges, it may be regarded as a functional compensatory response of the nervous system, similar to homeostatic regulation of neuronal activity. Therefore, we hypothesize that the hyperexcitability underlying NP results from excessive homeostatic compensation to the initial loss of activity and that stimulating neuronal activity will suppress this overcompensation and control NP. This hypothesis is supported by our preliminary data showing that enhancing cortical neuronal activity by either ontogenetic stimulation or focal drug release is effective in controlling pain in animal models of NP. In this project, we will employ a well-established transient spinal cord ischemia model of NP in mice to determine whether controlled ontogenetic stimulation of specific populations of cortical neurons or pharmacological enhancement of cortical activity will prevent this progression and control NP, and whether injury of the nervous system will induce pathological homeostatic regulation, which progresses to cortical hyperexcitability. The direct effect and mechanism of ontogenetic stimulation on neuronal hyperexcitability will be further determined. The success of this project will establish the role of excessive homeostatic compensation in the development of NP and will verify a novel strategy for controlling NP by stimulating neuronal activity. Establishing this nove strategy not only will provide a theoretical basis for the current use of cortical stimulation for P (e.g., repetitive transcranial magnetic stimulation), but also will open a door for discovering new drugs for controlling NP by promoting neuronal activity. Because of its unconventional concept, innovative approach, and significant relevance to public health, this proposal is particularly suited to the EUREKA mechanism.
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0.912 |
2014 — 2017 |
Beggs, John [⬀] Jin, Xiaoming Mackie, Ken |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Mri: Acquisition of a High-Density Microelectrode Array For Recording and Stimulating Hundreds of Neurons
An award is made to Indiana University, Bloomington, to acquire a 512 micro-electrode array instrument (512MEA) for recording and stimulating electrical activity in samples of brain tissue. The 512MEA can be used to measure how groups of several hundred neurons send information back and forth to each other. The ability to map information transfer in networks of this size is expected to be very valuable. Many theories predict that information transfer will change in networks of hundreds of neurons after learning, after exposure to drugs of addiction or toxins, after seizures and after traumatic injury. Other theories predict that brain networks process information in a nearly optimal way, an idea that has remained largely untested. Use of the 512MEA is therefore expected to provide new knowledge relevant to understanding how learning occurs, how drug addiction begins, how poisons affect brain health, how epileptic seizures start, how the brain responds to injury, and how the brain optimizes information processing. Ultimately, this work could benefit society by helping to improve teaching and learning in schools, by helping in the treatment of epilepsy patients, people exposed to harmful substances, war veterans, and by suggesting new ways to design brain-like computers. To maximize the number of students and laboratories using this device, it will be rotated between the Department of Physics, the Department of Brain and Psychological Sciences, and the Medical School.
The research and training opportunities that are opened by the 512MEA center on two topics of investigation: (1) emergent properties, and (2) information transfer. Emergent Properties: Many basic emergent properties of the brain like pattern recognition, associative memory, formation of cell assemblies, neuronal avalanches, synchronized pulses, and collective computations are predicted to arise first in populations of hundreds of interconnected neurons. Although most of these phenomena have been predicted for decades, they have remained largely unexplored for lack of proper instrumentation. The 512MEA would allow all of these topics to be researched in detail, many for the first time. Information transfer: It is almost completely unknown how information transfer differs in networks from naive animals and those that have learned; between networks exposed to neuro-active substances and those that have not; between developing networks and those that have matured. Because the 512MEA can record neural activity at millisecond resolution, it can identify which brain cell became active first in a chain of activity. This ability is crucial, as it will indicate the direction of influence between neurons. Optical methods of recording activity between hundreds of neurons often do not have this capability. The 512MEA can thus permit many of these topics to be researched for the first time.
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0.957 |
2018 — 2021 |
Horstmyer, Jeffrey Khizroev, Sakhrat [⬀] Jin, Xiaoming |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Goali: Collaborative - Magnetoelectric Nanodevices For Wireless Repair of Neural Circuits Deep in the Brain @ Florida International University
The GOALI project at the intersection of engineering and medicine aims to address the following gap in the broad area of neurodegenerative diseases. Stimulation of the neural network by electric fields can repair the abnormal neural activity responsible for various neurodegenerative diseases such as Alzheimer's Disease (AD) and many others. Further, recently it has been shown that electric fields have fundamental effects on cell fate and neurogenesis. However, the existing approaches such as (1) direct deep-brain stimulation (DBS) by establishing direct electrical contact to the neural network and (2) less-invasive indirect transcranial magnetic stimulation (TMS) don't provide spatial and temporal resolutions required for adequate control of the neural network at the cellular level to effectively cure these diseases using electricity, without causing any devastating side effects. This project fills this gap by implementing a nanotechnology approach, according to which magnetoelectric nanoparticles (MENs) are used to combine the main advantages of electric and magnetic fields to enable wirelessly controlled high-efficacy, high-specificity and high-selectivity stimulation of selective regions in the brain to treat specific neurodegenerative diseases without any side effects. The potential applications are far-reaching into engineering electromagnetic and multiferroic nanoparticle-driven systems which could impact the emerging field of personalized precision medicine, cognitive neuroscience, neuroimaging, clinical neurology, and psychiatry. The proposed system can help reverse engineer the brain and thus open a pathway to fundamental understanding of the brain. An important component of the project is to motivate underrepresented minorities to pursue cross-disciplinary degrees at the intersection of engineering and medicine. A special emphasis will be made to attract local K-12 and undergraduate students to continue their research at FIU and Indiana University.
The GOALI proposal aims to conduct comprehensive studies to engineer magnetoelectric nanoparticles (MENs) based system for wireless stimulation of local regions deep in the brain to repair disease specific impediments. MENs can bridge local intrinsic electric fields deep in the brain with magnetic fields and thus enable an external control of local electric stimulation for repairing neural circuits locally. Like traditional magnetic nanoparticles, MENs can be used as image contrast agents in magnetic resonance imaging and navigated across the blood-brain barrier via application of magnetic field gradients. In addition, unlike traditional nanoparticles, MENs display an entirely new property due to the presence of a non-zero magnetoelectric (ME) effect. The ME effect, which exists due to coupled magnetostrictive and piezoelectric components, allows to efficiently couple intrinsic electric fields deep in the brain to magnetic fields which in turn can be wirelessly controlled from outside the skull. Thus, MENs allow to use d.c. and a.c magnetic fields for separating the two functions, (i) application of a d.c. magnetic field gradient for image-guided navigation of MENs across BBB and into a disease-specific local region(s) and (ii) application of an a.c. magnetic field to stimulate this local region(s) locally via inducing local a.c. electric fields, respectively. Based on the physics of metastable systems, using a system of electromagnets, the nanoparticles can be effectively maintained in a quasi-diamagnetic state and thus moved to any point deep in the brain for further local electric stimulation via application of a.c. magnetic fields. Due to the ME effect, the image provided by MENs not only contains structural information but also reflects a local electric field due to the neuronal activity. All these effects will be studied in vitro and in vivo using animal models to understand field-controlled local effects of MENs on the underlying mechanisms of activation of neurons and synapses, the cortical neuronal activity, neuronal excitability, and synaptic transmission.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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0.954 |
2018 |
Blesch, Armin [⬀] Jin, Xiaoming |
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.) |
Sensorimotor Training and Cortical Mechanisms of Pain After Spinal Cord Injury @ Indiana Univ-Purdue Univ At Indianapolis
Abstract In addition to impairment of motor, autonomic and sensory function, severe pain is highly prevalent in patients after spinal cord injury. This project aims to better understand the cortical mechanisms and changes underlying the development of central neuropathic pain after spinal cord injury challenging the assumption that hyperexcitability of neuronal circuits can only be modified by directly blocking excitation or increasing the activity of inhibitory circuits. Our previous work has characterized the onset and maintenance of chronic central neuropathic pain in a mouse model of contusion injury. Our preliminary data also show that sensory cortical activity is initially decreased after a transient spinal cord ischemia followed by hyperactivity paralleling the onset of pain behavior. This hyperactivity and the associated pain behavior can be diminished by optogenetic stimulation of somatosensory cortex early after injury. In addition, we have shown that treadmill training can prevent the development and partially reverse pain-associated behavior in mice. We now aim to characterize in detail changes in somatosensory cortical activity after traumatic spinal cord injury in mice using patch- clamping and in vivo calcium imaging in transgenic mice. We also aim to determine whether modulating cortical activity by somatosensory training can modulate cortical hyperactivity after spinal cord injury and thereby ameliorate neuropathic pain. Thereby, we will advance our understanding of the development and maintenance of chronic pain after spinal cord injury, identify cortical mechanisms underlying the development of chronic pain that can be translated into novel pharmacological and rehabilitative treatments that interfere with homeostatic plasticity for a comprehensive pain management.
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0.912 |