Key Dates

Related Announcements

• September 27, 2023 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship (Parent F32). See NOFO PA-23-262
• September 23, 2023- Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship for Students at Institutions Without NIH-Funded Institutional Predoctoral Dual-Degree Training Programs (Parent F30). See NOFO PA-23-261
• September 12, 2023- Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (Parent F31-Diversity). See NOFO PA-23-271
• August 17, 2023- Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31). See NOFO PA-23-272
• August 16, 2023 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship for Students at Institutions with NIH-Funded Institutional Predoctoral Dual-Degree Training Programs (Parent F30). See NOFO PA-23-260
• March 26, 2021 - Cutting-Edge Basic Research Awards (CEBRA) (R21 Clinical Trial Optional). See NOFO PAR-21-208
• May 20, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185
• May 20, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed). See NOFO PA-20-195
• May 7, 2020 - NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed). See NOFO PA-20-200
• May 6, 2020- Mentored Research Scientist Development Award (Parent K01--Independent Clinical Trial Not Allowed). See NOFO PA-20-190
• May 5, 2020- NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Not Allowed). See NOFO PA-20-188 

Issued by

National Institute on Drug Abuse (NIDA)

Purpose

The purpose of this Notice of Special Interest (NOSI) is to encourage innovative research on the roles of oligodendrocytes and myelination in addiction-related neurocircuit functions.

Background

Myelin formation and remodeling play essential roles in the brain throughout life. Myelination is one of the fundamental mechanisms that coordinates appropriate formation, growth and integrity of brain development and fine-tunes circuit functions. Because myelination exerts an additional form of plasticity in that it can mediate long-lasting changes in neural circuit function, experience-induced myelination has been associated with cognitive function, attention, learning, and memory. However, the mechanisms by which myelination is involved in behaviors relevant to substance use disorder (SUD) or addiction are unknown. Likewise, the effects of drug use on myelination as part of the pathophysiology of addiction have not been well-studied.

Early-life stress is associated with altered oligodendrocyte function and decreased myelination and can cause long-lasting changes in brain plasticity that lead to increased drug use behaviors. Many abused substances also have profound impacts on brain myelination. Recent findings showed white matter impairments in patients with cocaine use disorder that were associated with a decrease in myelination-related proteins in the prefrontal cortex. The endocannabinoid system can modulate oligodendrocyte functions in different physiopathological settings, and Δ9-Tetrahydrocannabinol (THC) administration can promote oligodendrocyte maturation and CNS myelination via CB1 and CB2 cannabinoid receptors. Evidence also suggests that opioid signaling has significant impacts on developmental oligodendrocyte differentiation and brain myelination. And exogenous opioids may alter the timing of developmental brain myelination. Early histological analyses and imaging demonstrated that heroin and morphine misuse in adult humans can result in severe myelin damage. Acute overdose of prescription opioids can produce similar myelin damage in the adult brain. Conversely, pre-clinical studies suggest that THC promotes oligodendrocyte development and CNS myelination. It is unclear how changes in myelination during brain development may affect drug use behaviors later in life, also, whether alterations in myelin dynamics are associated with drug-induced behavioral changes remains unknown.

Recent evidence suggests that myelin may be adaptable in response to circuit activity. However, the roles of myelination dynamics in circuit functional regulation throughout life are unknown. Subtle changes in the overall pattern of myelination along an axon could profoundly change neuronal activities and circuit functions. Recent evidence suggest microglia and astrocytes may influence neuronal excitability by stabilizing myelin integrity. Additionally, studies show that microglia depletion can dysregulate myelination, and mild COVID can cause persistent microglia reactivity and myelin dysregulation. Since glia-neuron communications and myelination contribute to re-wiring neural circuits, it is important to understand how neuronal activities change oligodendrocyte function, especially how drugs can affect CNS resident cells to coordinate myelination processes. Understanding the underlying mechanisms of myelination dynamics involved in the addiction circuitry could present new avenues for developing diagnostics and treatment for addiction.

Research Objectives

• Understand how acute or chronic substance use affects oligodendrocyte dynamics and myelination homeostasis throughout different stages of life.
• Investigate mechanisms of microglia-regulated myelin growth and integrity in the context of SUD.
• Investigate how CNS resident cells mediate myelin dynamics and their interactions with extracellular matrix components in the context of SUD.
• Target neuromodulation therapy to modulate neural activity required for myelination in the neurocircuitry of addiction.
• Explore molecular and cellular signaling pathways that mediate myelin dynamics.
• Leverage tools and in vivo imaging studies to understand the dynamics of myelination in the context of SUD.
   

Application and Submission Information

This notice applies to due dates on or after June 5, 2024 and subsequent receipt dates through January 8, 2027

Submit applications for this initiative using one of the following notices of funding opportunities (NOFOs) or any reissues of these announcements through the expiration date of this notice.

• PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed).
• PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed).
• PAR-21-208 - Cutting-Edge Basic Research Awards (CEBRA) (R21 Clinical Trial Optional).
• PA-20-200 - NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed).
• PA-20-188 - NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Not Allowed).
• PA-20-190 - Mentored Research Scientist Development Award (Parent K01--Independent Clinical Trial Not Allowed).
• PA-23-260 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship for Students at Institutions with NIH-Funded Institutional Predoctoral Dual-Degree Training Programs (Parent F30).
• PA-23-261 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship for Students at Institutions Without NIH-Funded Institutional Predoctoral Dual-Degree Training Programs (Parent F30).
• PA-23-262 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship (Parent F32).
• PA-23-271 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (Parent F31-Diversity).
• PA-23-272 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31).

All instructions in the SF424 (R&R) Application Guide and the notice of funding opportunity used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-DA-25-028” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed notice of funding opportunity.

Scientific/Research Contact(s)

Shang-Yi Anne Tsai, Ph.D.
National Institute on Drug Abuse (NIDA)
Phone: 301-827-5842
Email: stsai@nih.gov