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FGF Receptor Signaling in Oligodendrocytes Regulates Synaptic Plasticity, Learning, and Memory in the Adult Brain
1Department of Neuroscience, University of Connecticut Medical School, Farmington, Connecticut, USA.
Glia
|December 8, 2025
Summary
Fibroblast Growth Factor Receptor (FGFR) signaling in oligodendrocytes (OLs) is crucial for maintaining synaptic activity and memory in adult brains. Loss of FGFR1/2 signaling impairs long-term potentiation and memory, revealing a novel role in OL-neuron communication.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Oligodendrocytes (OLs) myelinate axons, supporting neuronal function.
- Fibroblast Growth Factor Receptor (FGFR) signaling is known to be vital for oligodendrocyte precursor cell (OPC) development and myelin maintenance.
- The role of OL-lineage cells in adult synaptic function and memory remains largely unexplored.
Purpose of the Study:
- To investigate the role of FGFR1/2 signaling in adult OL-lineage cells on synaptic plasticity and memory.
- To determine if FGFR1/2 signaling in OLs impacts neuronal communication and cognitive functions during aging.
Main Methods:
- Utilized conditional knockout mouse models with tamoxifen-inducible FGFR1/2 ablation in OL-lineage cells.
- Assessed synaptic function using electrophysiology (long-term potentiation).
- Evaluated memory and learning through hippocampal-based behavioral tests.
- Examined synaptic structure and markers of neurodegeneration and neuroinflammation.
Main Results:
- Loss of FGFR1/2 signaling in adult OLs impaired long-term potentiation (LTP) and hippocampal memory.
- Reduced docked synaptic vesicles and increased beta-amyloid precursor protein (β-APP) accumulation were observed.
- No significant changes in OL/OPC numbers, myelin integrity, or glial activation were detected.
- Conditional ablation of FGFR1 or FGFR2 individually also impaired LTP.
Conclusions:
- FGFR1/2 signaling in adult OL-lineage cells is critical for maintaining synaptic plasticity and memory.
- This signaling pathway plays a previously unrecognized role in OL-neuron communication for cognitive function.
- FGFR1/2 signaling in OLs is essential for synaptic health and memory, independent of myelin integrity or neuroinflammation.
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