1999 — 2002 |
Corbin, Joshua G |
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. |
Glial Cells Missing Gene in Mammalian Gliogenesis @ New York University School of Medicine
Work proposed in this fellowship is aimed at gaining a greater understanding of the genetic mechanisms that regulate the control of glial development in vertebrates. Toward this aim, the role that the glial cells missing (gcm) gene plays in this process will be investigated. Two gain of function approaches are proposed to address this question. In the first specific aim, a standard transgenic approach will be utilized to drive ectopic expression of this gene to the mouse embryonic nervous system. In the second and third specific aims, a retroviral approach is proposed better understand the mechanism of how this gene may be involved in gliogenesis in the mammalian CNS. Specific aims two and three will be accomplished by the use of the novel technology of ultrasound guided microinjection to deliver engineered retrovirus to the early embryonic nervous system of the mouse. Results from this work can potentially lead to further insight into how cancers of glial origin arise, and novel gene therapy approaches designed to correct detrimental genetic mutations.
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0.904 |
2006 — 2020 |
Corbin, Joshua G |
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. |
Development of the Basal Telencephalic Limbic System @ Children's Research Institute
The goal of the renewal proposal is to uncover how developmental programs establish brain circuitry controlling critical social and non-social behaviors. Our previous findings studying amygdala development have lead to a developmental transcription factor-centric model in which we hypothesize that development, connectivity and innate behavioral specificity of limbic subcircuits are differentially controlled by the embryonic expressed transcription factors, Dbx1 and Foxp2. We will test this model in three aims in which we will: 1) determine the limbic connectivity patterns of Dbx1- and Foxp2-derived neurons (Specific Aim 1), 2) the cell adhesion molecules regulated by Dbx1 and Foxp2 (Specific Aim 2) and 3) the function of Dbx1 and Foxp2 in the formation/maintenance of medial amygdala circuit function and social and non- social innate behaviors (Specific Aim 3). Testing of this hypothesis will be accomplished using a diverse and powerful combination of state of the art conditional mouse genetics, neuronal circuit mapping and gene profiling approaches along with electrophysiology and innate behavior tasks. By comprehensively integrating data from multiple levels of analyses, we will uncover how developmental programs establish brain circuitry that controls motivational and innate social and non-social behaviors. Moreover, as amygdala dysfunction is a prime feature of a host of prevalent human social and emotional disorders, including drug-addictive behaviors and autism spectrum disorders, this work is critical toward understanding how brain circuit dysfunction leads to substance abuse and addictive behaviors.
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0.931 |
2012 |
Corbin, Joshua G Huntsman, Molly-Maureen |
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. |
Testing the Excitability of Inhibitory Neurons @ University of Colorado Denver
DESCRIPTION (provided by applicant): Neurological disorders such as epilepsy and Fragile X Syndrome (FXS) are characterized with imbalances in excitatory and inhibitory neurotransmission. Patients with FXS exhibit a hyperexcitable phenotype evidenced by severe cognitive deficits, increased incidence of recurring seizures, social anxiety and hypersensitivity to sensory stimuli. We hypothesize that defects in inhibitory neurotransmission in primary somatosensory cortex underlie aspects of the hyperexcitable phenotype of FXS, including its comorbidity with epilepsy. In this project, we use a multidisciplinary approach combining electrophysiological and anatomical analyses with mouse genetic rescues to study the Fragile X phenotype in a cortical area relevant for both cognitive and sensory dysfunction. Our primary goals are to determine the mechanism of synaptic and network dysfunction in FXS. We will examine inhibitory neuron dysfunction through the view of two complementary theories that are hypothesized to lead to the hyperexcitable phenotype observed in FXS. We will additionally test whether altered excitability in inhibitory circuits can be rescued genetically in FXS mutant mice.
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0.931 |
2013 — 2017 |
Corbin, Joshua G |
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. |
Assembly and Function of Olfactory Circuitry From Dbxl-Derived Neural Progenitors @ Children's Research Institute
DESCRIPTION (provided by applicant): How neural developmental programs are linked to the establishment of mature brain circuits and related behavior remains a central question of neuroscience. Our previous studies revealed that a class of neural progenitors defined by the expression of the homeodomain encoding transcription factor, Dbx1, are dedicated for the generation of subsets of neurons of the limbic system including the olfactory bulb. Based on these findings, we hypothesize that Dbx1+ progenitors located in a distinct embryonic niche generate a functionally distinct interconnected subset of olfactory bulb output neurons that are dedicated to the processing of subsets of innate behaviors. Testing of this hypothesis will be accomplished using a combination of multidisciplinary approaches including genetic fate mapping, optogenetics and innate behavioral testing.
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0.931 |
2020 |
Corbin, Joshua G |
S10Activity Code Description: To make available to institutions with a high concentration of NIH extramural research awards, research instruments which will be used on a shared basis. |
Vevo 3100 High Resolution Ultrasound For Small Animal Imaging @ Children's Research Institute
Project Summary We propose to acquire a VisualSonics Vevo 3100 preclinical ultrasound imaging system to support a large cohort of NIH-funded investigators at the Children?s Research Institute (CRI) of Children?s National Medical Center (CNMC). This system will be utilized by at least 15 principal investigators for a wide array of applications including cardiovascular, developmental biology, urology, neuroscience and cancer biology research programs. Currently there is no onsite imaging system that can address the needs of these investigators for high resolution imaging and real-time physiological measurements. Acquisition of the Vevo 3100 system will allow for ultra-high frequency ultrasound imaging of rodent models of human diseases to simultaneously obtain in vivo anatomical, hemodynamic, functional and physiological data in real-time and with an imaging resolution down to 30 ?m. The Vevo 3100 System will replace our obsolete Vevo 770 System (circa 2006), which is housed in the District of Columbia Intellectual and Developmental Disabilities Research Center (DC-IDDRC) Animal Neurobehavioral Evaluation Core (ANEC) located within our research animal facility. Compared to the Vevo 3100, the Vevo 770 has outdated technology with lower resolution imaging capacity, single array, mechanical transducers and slower image acquisition. Novel features of the Vevo 3100 System will allow for applications not possible with the Vevo 770 in a fraction of the time such as Color Doppler to measure direction and velocity of blood flow, rapid 3D and 4D imaging capabilities, functional analysis of the heart and vasculature using Vevo Strain and Vevo Vasc software as well as contrast imaging. The Vevo 3100 System will be made available to members of the DC- IDDRC and other NIH funded investigators at CNMC through the infrastructure of the ANEC. The ANEC is staffed with a research director (Joshua Corbin, PhD) and a full-time manager (Li Wang, MD) and our investigator base includes individuals with extensive experience utilizing high frequency ultrasound for animal imaging. Notably, Linda Leatherbury, MD and Joshua Corbin, PhD have over 45 years combined experience training and utilzing high frequency ultrasound in rodents and will play a key role in training new investigators on the Vevo 3100 and data analysis. As director of the ANEC, Dr. Corbin will manage and oversee maintenance of the instrument, design and implement appropriate training programs, method development as well as compliance management. We will also create an interest group to disseminate results and approaches within our research community. Members of the advisory committee will assist the principal investigator and the broader user group to collectively managing future modifications to the user base and prioritization of access. CNMC will support workstations throughout the institution so that investigators can analyze their data in a convenient setting. Acquisition of the Vevo 3100 imaging system will address a large existing unmet scientific need, positively impact pediatric related NIH-funded research programs and create new collaborative venues for complementary basic and translational research programs that fit within the mission of the Children?s Research Institute.
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0.931 |
2021 |
Corbin, Joshua G Sorrells, Shawn (co-PI) [⬀] |
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.) |
Origin and Timing of Development of Late-Maturing Neurons in the Amygdala @ Children's Research Institute
Project Summary The amygdala is a major processing center for emotional and social behaviors, aspects of which are altered in developmental disorders such as Autism Spectrum Disorders (ASD). In humans, the paralaminar nucleus of the amygdala (PL), located adjacent to basolateral amygdala amygdala (BLA), contains a large population of immature neurons that persist into post-natal stages, well past the maturational time course of the overwhelming majority of neurons in the brain. Our recent studies have revealed that human PL neurons mature prominently during childhood and adolescence (Sorrells et al., Nature Communications, 2019). This raises the intriguing possibility that these neurons are essential for social/emotional changes that occur during critical periods of postnatal development. Our preliminary data reveal that this population is also present in mice. This opens up an exciting opportunity to use the mouse to model this interesting neuronal population. The goals of this exploratory R21 application are to: 1) characterize the post-natal morphological, molecular and electrophysiological maturational profiles of mouse PL neurons during the pre-pubertal critical period temporally coinciding with emergence of emotional processing in humans and 2) determine the developmental timing and origin of mouse PL neurons. As embryonic origin and identity are intimately tied to adult neuronal function, these studies are also a important first step to ultimately dissecting neural connectivity, function and role that these specialized cells play in neuro-typical and -atypical social-emotional development.
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0.931 |