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Merlin modulates process outgrowth and synaptogenesis in the cerebellum
1Institute of Anatomy, Anatomy and Cell Biology, Bonn University, 53115, Bonn, Germany.
Brain Structure & Function
|June 6, 2019
Summary
Merlin, a protein linked to Neurofibromatosis type 2, fine-tunes synapse organization in the cerebellum. Its absence alters presynaptic terminal size and function, impacting neuronal communication without affecting overall brain development.
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Neurofibromatosis type 2 (NF2) is associated with tumors, often glial-derived.
- The Nf2 gene product, Merlin, is present in central nervous system (CNS) neurons, but its function there is unclear.
- Merlin's role in neuronal development and synaptic function requires further investigation.
Purpose of the Study:
- To investigate the function of Merlin in cerebellar neurons.
- To determine Merlin's impact on synaptic structure and function in the CNS.
- To elucidate Merlin's role in neuronal development and associated behaviors.
Main Methods:
- Utilized isoform-specific Merlin-deficient mice models (L7Cre;Nf2fl/fl and Math1Cre;Nf2fl/fl).
- Analyzed presynaptic terminal morphology using vGluT1 and vGluT2 staining.
- Measured miniature excitatory postsynaptic currents (mEPSCs) to assess synaptic function.
- Evaluated ultrasonic vocalization as a behavioral readout.
Main Results:
- Merlin deficiency in Purkinje cells (PCs) led to enlarged presynaptic terminals and increased mEPSC amplitude.
- Merlin deficiency in granule cells (GCs) resulted in altered vGluT1/vGluT2 cluster sizes and increased mEPSC frequency.
- Rac1-Cofilin signaling was activated in Merlin-deficient GCs, impacting the cytoskeleton.
- Synaptic alterations correlated with changes in ultrasonic vocalization behavior.
Conclusions:
- Merlin is crucial for regulating pre- and post-synaptic terminal organization in the cerebellum.
- Merlin's function is specific to synaptic organization, not overall cerebellar development.
- Dysregulation of Merlin impacts neuronal communication and related behaviors.
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