Jason Tait Sanchez - US grants
Affiliations: | Oto-HNS | University of Washington, Seattle, Seattle, WA | |
| Northwestern University, Evanston, IL |
Area:
Cell Imaging & Electrophysiology, Hearing SciencesWe are testing a new system for linking grants to scientists.
The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Jason Tait Sanchez is the likely recipient of the following grants.| Years | Recipients | Code | Title / Keywords | Matching score |
|---|---|---|---|---|
| 2009 — 2011 | Sanchez, Jason Tait | 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. |
Developmental Profile of Glutamate Receptors in Nucleus Laminaris @ University of Washington DESCRIPTION (provided by applicant): Understanding auditory development requires knowledge of events that influences the ontogeny of neural structure and function. This research will examine the developmental role of glutamate and its receptors in a circuit used for binaural hearing. Nucleus laminaris (NL), a third-order auditory structure in birds, provides an ideal model system to address this issue. NL receives excitatory information from nucleus magnocellularis and functionally, these glutamatergic inputs provide initial cues for sound localization. It is unclear how ionotropic glutamate receptors (iGluRs) develop in NL and more importantly, the functional role they play in synaptogenesis, synaptic refinement, and dendritic arborization. This research will characterize the developmental profile of the AMPA- and NMDA-type glutamate receptors (AMPA-R and NMDA-R, respectively) and determine how developmental changes in their biophysical response properties influence the structure and function of NL neurons. My proposed research will address a general question of synaptic development. What are the properties and developmental significances of glutamate transmission and receptor function at NL synapses? My hypotheses are: (1) excitatory postsynaptic currents (EPSCs) in NL are mediated by both AMPA- and NMDA-Rs, (2) biophysical properties of AMPA- and NMDA-Rs are regulated developmentally and tonotopically and (3) activity mediated by NMDA-Rs is essential for NL structure and function. The specific aims to test these hypotheses are: (1) characterize synaptic iGluR function developmentally and tonotopically in NL and (2) block NMDA-R activity and characterize structural and functional changes in NL. The general methods I will use to test these aims are whole-cell voltage clamp recordings from acute brainstem slices, pharmacological manipulations of iGluRs, and NMDA-R inactivation from culture brainstem slices. Lay description: The proposed research studies how excitatory events during development establish connections between auditory neurons responsible for binaural hearing. Understanding how these events influence the development of auditory properties may contribute to the improvement of appropriate therapies for individuals deprived of auditory information early in life. |
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| 2015 — 2017 | Sanchez, Jason Tait | R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Mechanisms Regulating Synaptic Function in the Developing Auditory System @ Northwestern University ? DESCRIPTION (provided by applicant): The goal of this research is to identify mechanisms that give rise to fast neural encoding of sound critical for normal auditory function. However, developmental mechanisms are poorly understood in the brainstem, where deficits in fast neural encoding underlie aspects of auditory temporal processing disorders. At mature auditory synapses, fast neural encoding is mediated by AMPA-type glutamate receptors (AMPA-Rs) due largely in part to their subunit arrangement, which is distinct from other brain regions. Their unique subunit arrangement raises important biological questions: are the mechanisms that regulate the development of specialized AMPA- R properties in the auditory system similar to mechanisms that regulate AMPA-Rs elsewhere in the brain? If so, what mechanisms govern this different arrangement of AMPA-R subunits? If not, are alternative mechanisms regulating AMPA-Rs exclusive to the auditory system? This study will address these questions by investigating the regulation of synaptic AMPA-Rs properties in the avian auditory brainstem. Elsewhere in the developing brain, NMDA-Rs assist in regulating normal AMPA-R properties and during specific diseased states; NMDA-Rs are implicated as a molecular target in controlling synaptic AMPA-R dysfunction. NMDA-Rs also play a negative role in diseases of the auditory system, including tinnitus, noise- induced hearing loss and neural presbycusis. However, the causal role NMDA-Rs plays in regulating synaptic AMPA-Rs and the extent to which they contribute to fast neural encoding of sound in the developing auditory brainstem are not known. This study will test the hypothesis that the establishment of fast neural encoding requires NMDA-R dependent regulation of synaptic AMPA-R properties in the developing brainstem, critical for precise auditory temporal processing abilities. Investigating the regulator role of NMDA-Rs on AMPA-Rs will be a significant first step in understanding pathologies associated with auditory temporal processing disorders. Using innovative methods, the project aims to determine the extent to which NMDA-Rs (1) regulate the number and subunit composition of synaptic AMPA-R in the developing avian nucleus magnocellularis (NM) and (2) to determine the extent to which temporal speed and precision are mediated by AMPA-Rs at functionally mature NM synapses following genetic manipulation of NMDA-Rs. I will combine in-ovo genetic manipulations, pharmacological/biochemical assays, and in-vitro patch clamp electrophysiology to test the above Aims during developmental time periods corresponding to synapse formation, hearing onset, and functional maturation. Gaining an understanding of NMDA-Rs contribution to synaptic development and refinement should shed light on the role of subunit-specific AMPA-Rs in the auditory system. A better understanding of molecular-level NMDA-R mechanisms may identify pharmacological targets to improve disorders in which synaptic AMPA-R dysfunction has either a direct or causal role in pathologies related to auditory temporal processing. |
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| 2020 — 2021 | Sanchez, Jason Tait | 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. |
Molecular Mechanisms of Tonotopy Development in the Brain Stem @ Northwestern University ABSRACT Normal nervous system maturation is dependent on neurotrophin signaling. Neurotrophins are proteins, and along with their signaling receptor pathways, help regulate the development, maintenance and function of vertebrate nervous systems, making it a dynamic factor that promotes biologically relevant tasks. Irregular neurotrophin signaling results in pathophysiological conditions throughout the peripheral and central nervous system. In the auditory periphery for example, this includes atypical arrangement of innervation patterns along the frequency gradient (i.e., tonotopic axis) of the inner ear and hearing loss. Beyond the auditory periphery of all vertebrates, however, the establishment of functional specialization in the central auditory pathway via neurotrophin signaling are lacking. Understanding gradients of neurotrophin signaling is a significant and timely problem in developmental neurobiology in general, and the avian auditory pathway proves to be a particularly advantageous model system for experimentally examining it. A better understanding of normal auditory circuit assembly ? along with the unique functional properties of brainstem neurons ? will provide a significant foundation for developing stem cell-based therapies for auditory-related disorders. Stem cell-derived auditory neurons will only prove useful, therapeutically, if they are able to re-create specialized functional properties that are characteristic of normal auditory circuit maturation. A careful characterization of neurotrophin signaling, the underlying molecular mechanism by which they operate, the role it plays in establishing normal auditory properties and the functional consequence of altering this biological process is necessary and appropriate. The research proposed here aims at addressing these issues by providing a comprehensive understanding of developmental properties associated with neurotrophin signaling and its role in establishing normal functional phenotypes along the tonotopic axis in the cochlear nucleus: a brainstem structure essential for the temporal processing of sound. |
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