CRMP2 conditional knockout changes axonal function and ultrastructure of axons in mice corpus callosum

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Collapsin response mediator protein 2 (CRMP2) is crucial for neurodevelopment and neuronal structure.
• CRMP2 expression persists in adult brain regions like the corpus callosum (CC) and is linked to schizophrenia (SZ).
• CRMP2 dysfunction is implicated in brain connectivity disorders.

Purpose of the Study:

• To investigate the impact of CRMP2 deletion on white matter structure and function in a mouse model relevant to SZ.
• To elucidate the role of CRMP2 in corpus callosum (CC) integrity and brain connectivity.

Main Methods:

• Utilized a CRMP2 conditional knockout (CRMP2-cKO) mouse model.
• Employed multielectrode electrophysiology (MEA) to assess CC function (conduction velocity).
• Applied light and Serial Block-face Scanning Electron Microscopy (SBF-SEM) for detailed CC structural analysis.

Main Results:

• CRMP2-cKO mice exhibited increased CC conduction velocity (CV) and compound action potential (CAP) speeds.
• A significant reduction in CC volume was observed in CRMP2-cKO mice.
• Abnormally smaller axons were found in CRMP2-cKO mice, despite no changes in oligodendrocyte numbers, size, myelin thickness, or node of Ranvier structure.

Conclusions:

• CRMP2 deficiency leads to white matter alterations, including smaller axons and altered CC volume.
• These structural changes in CRMP2-cKO mice correlate with functional changes in CC conductivity.
• Findings provide insights into the role of CRMP2 in white matter integrity and its potential contribution to schizophrenia pathophysiology.