# Examining the regulation of resident mRNAs in myelinplasticity

> **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2024 · $74,284

## Abstract

PROJECT SUMMARY
 Synaptic plasticity is well accepted as the basis of behavioral adjustability in the face of a constantly
changing environment. Our lived experience is transmitted to our brain as electrical impulses along axons.
Oligodendrocytes (OLs) increase the rate at which these electrical impulses are transmitted by insulating
axons with myelin sheaths. Surprisingly, motor learning, sensory stimulation, and social enrichment induce the
differentiation of precursor cells into myelinating OLs resulting in quantifiable structural changes in white
matter. These findings point to myelin plasticity as a concurrent, and equally important contributor to the
adaptability of neural circuits. However, the molecular and cellular mechanisms underlying myelin plasticity are
not well understood.
 Single OLs can give rise to sheaths of different lengths and thicknesses to accommodate the needs of
diverse axons. These observations suggest a local and independent regulation of myelination at the level of
individual sheaths. How do sheaths assess the needs of specific axons? Action potentials cause axons to, not
only release vesicles at their terminal ends, but also along their shafts. Our lab and others have shown that
axons signal to myelin sheaths via these alternative release sites and that myelin sheaths express the
canonical post-synaptic factors required to interpret these signals. These data suggest that the use of a shared
transmission machinery enables synaptic and myelin plasticities to occur in parallel as a response to the same
stimulus.
 While some components of axo-myelin communication have been elucidated, the intracellular
mechanisms bridging signal receipt to myelin production remain unknown. In dendrites, the localization of
mRNA transcripts and ribosomes to individual spines support their rapid, tailored adaptive responses.
Similarly, diverse groups of mRNAs, along with ribosomes localize to myelin sheaths raising the possibility that
local RNA translation underlies the ability of individual OL sheaths to fine-tune their responses to signals from
various axons. Due to the dynamic nature of RNA translation, it would be best understood if studied in vivo.
However, limitations in technological approaches stood in the way for decades. Using diverse transgene
expression systems, protein photoconversion technology, and my expertise with 2-photon laser severing, I will
determine if local translation of myelin-resident transcripts occurs in zebrafish. Additionally, I will investigate
whether the myelin localization of an enriched group of transcripts we identified contributes to myelin plasticity.
To accomplish this, I will create a loss-of-function mutation of Khdrbs1, an RNA binding protein predicted to
bind to members of this enriched group. Finally, I will test if manipulating neuronal activity alters the translation
of targeted myelin resident mRNAs. This work will add to our understanding of how axo-myelin exchanges
impact the efficiency of...

## Key facts

- **NIH application ID:** 11023020
- **Project number:** 5F32NS131216-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** KADIDIA PEMBA ADULA
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,284
- **Award type:** 5
- **Project period:** 2023-05-09 → 2026-05-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11023020

## Citation

> US National Institutes of Health, RePORTER application 11023020, Examining the regulation of resident mRNAs in myelinplasticity (5F32NS131216-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11023020. Licensed CC0.

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