Leveraging adolescent plasticity mechanisms to enhance adult frontal dopaminergic circuit function
NIDA - National Institute on Drug Abuse
About This Grant
Abstract My goal is to head an independent research program studying dopaminergic system dysfunction in neurodevelopmental disorders. I have extensive in vivo two-photon microscopy, neural circuit dissection, microglial physiology, and behavioral assay experience. Under my proposed training plan, I will work closely with my co-mentors, Drs. Kuan Wang, Zhigang He, Yi Zuo, and Julie Fudge to broaden and strengthen my research expertise to prepare for full research independence. Dr. Wang is an expert in the developmental plasticity and function of dopaminergic projections to the frontal cortex and in vivo imaging. Dr. He is an expert in sequencing and bioinformatic analyses of transcriptomic changes in microglia in response to CNS milieu disruption. Dr. Zuo is an expert on behavioral assays and circuit plasticity. Dr. Fudge is an expert in the dopaminergic system and psychiatric conditions. Collectively, my mentorship team and experimental plans will provide me with the technical skills and conceptual expertise to become an independent researcher in the fields of dopaminergic development and neuroimmune interactions. The Del Monte Institute of Neuroscience will provide a rich and collaborative training environment with an extensive network of investigators working on neurodevelopmental disorders within the URMC UR-IDDRC. In the Wang Lab, I have explored the mechanisms which drive mesocortical plasticity. Previous published work in the Wang lab established that the mesocortical dopaminergic projections from the ventral tegmental area (VTA) to the frontal cortex undergo activity dependent axonal bouton formation in response to VTA stimulation in adolescents but not adults. However, dopamine receptor 2 (D2R) inhibition paired with stimulation reopens adult plasticity. Interestingly, chemogenetic stimulation of dopaminergic VTA projections during adolescence ameliorates circuit and behavioral deficits in mice with genetic mutations disrupting mesocortical circuit function. My postdoctoral work shows that activity-dependent changes in the adolescent mesocortical circuit increase microglial surveillance of the parenchyma and microglial contacts with axonal boutons and that DR manipulation disrupts these interactions. My immediate goals are to understand the signals which regulate mesocortical dopaminergic plasticity, and to evaluate the therapeutic potential of reopening plasticity after developmental insult. (Aim 1) I will evaluate if microglia are necessary for the reopening of mesocortical plasticity in adult animals. (Aim 2) I will determine if reopening plasticity in adult mice with circuit disruptions from juvenile Δ-9-tetrahydrocannabinol exposure is effective at rescuing both dopaminergic hypofrontality and behavioral deficits. (Aim 3) I will use single-cell sequencing to identify changes in dopaminergic receptor signaling pathways between adolescent and adult animals which close the window of mesocortical plasticity. These experiments will provide a mechanistic understanding of mesocortical plasticity regulation and they will evaluate the therapeutic potential of reopening plasticity in the adult mesocortical circuit.
Grant Summary
Leveraging adolescent plasticity mechanisms to enhance adult frontal dopaminergic circuit function is a NIDA - National Institute on Drug Abuse grant providing up to $157K for university, nonprofit, healthcare org. Applications are due 2031-04-30 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $157K
2031-04-30
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- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
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Leveraging adolescent plasticity mechanisms to enhance adult frontal dopaminergic circuit function: Frequently Asked Questions
Who is eligible for the Leveraging adolescent plasticity mechanisms to enhance adult frontal dopaminergic circuit function?
Leveraging adolescent plasticity mechanisms to enhance adult frontal dopaminergic circuit function is offered by NIDA - National Institute on Drug Abuse and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Leveraging adolescent plasticity mechanisms to enhance adult frontal dopaminergic circuit function provide?
Leveraging adolescent plasticity mechanisms to enhance adult frontal dopaminergic circuit function provides up to $157K per award from NIDA - National Institute on Drug Abuse. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Leveraging adolescent plasticity mechanisms to enhance adult frontal dopaminergic circuit function deadline?
Applications for Leveraging adolescent plasticity mechanisms to enhance adult frontal dopaminergic circuit function are due 2031-04-30 (open). Because deadlines can change, verify the date with the funder, NIDA - National Institute on Drug Abuse, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Leveraging adolescent plasticity mechanisms to enhance adult frontal dopaminergic circuit function?
To apply for Leveraging adolescent plasticity mechanisms to enhance adult frontal dopaminergic circuit function, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIDA - National Institute on Drug Abuse.