3D Super-Resolution Imaging of PSD95 Reveals an Abundance of Diffuse Protein Supercomplexes in the Mouse Brain
2024

3D Imaging of PSD95 in the Mouse Brain

Sample size: 3 publication 10 minutes Evidence: high

Author Information

Author(s): Daly Sam, Bulovaite Edita, Handa Anoushka, Morris Katie, Muresan Leila, Adams Candace, Kaizuka Takeshi, Kitching Alexandre, Spark Alexander, Chant Gregory, O′Holleran Kevin, Grant Seth G. N., Horrocks Mathew H., Lee Steven F.

Primary Institution: Yusuf Hamied Department of Chemistry, University of Cambridge

Hypothesis

How is PSD95 organized in the mouse brain at a nanoscale level?

Conclusion

The study reveals that most PSD95 molecules exist as a diffuse population outside of synapses, rather than being confined to postsynaptic densities.

Supporting Evidence

  • 3D imaging allowed for a more accurate classification of PSD95 molecular arrangements.
  • Over 90% of PSD95 was found to be in a diffuse state rather than clustered in synapses.
  • Two populations of PSD95 dimers were identified with specific separation distances.

Takeaway

Scientists looked at a protein called PSD95 in mouse brains and found that most of it is spread out in a cloud, not just in the places where brain signals happen.

Methodology

The study used three-dimensional super-resolution microscopy to analyze the spatial arrangement of over 8 million PSD95 molecules in mouse brain tissue.

Limitations

The lower sensitivity of the DHPSF method may have led to lower apparent nanocluster densities compared to previous studies.

Participant Demographics

Adult 2- to 3-month-old heterozygous PSD95-mEos2 mice were used.

Digital Object Identifier (DOI)

10.1021/acschemneuro.4c00684

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