Table 1.
List of super-resolution microscopy techniques
TechniquePrincipleResolutionCommentsApplications in spines and synapses
Lateral (XY)Axial (Z)
CLSM  250 nm 500 nm   
TPLSM Two-photon excitation 350 nm 700 nm Deeper tissue penetration; adaptive optics further improve Helmchen and Denk, 2005; Ji, 2017  
STED Stimulated emission (Vicidomini et al., 2018) 20–70 nm 500 nm 3-D STED increases axial resolution; chronic in vivo imaging is possible Nägerl et al., 2008; Berning et al., 2012; Pfeiffer et al., 2018  
SIM Moiré effect with structured illumination (Wu and Shroff, 2018) 100 nm 250 nm No need for special fluorophores; limited resolution improvement Kashiwagi et al., 2019; Li et al., 2020  
SMLM (PALM, STORM) Photoactivation, photoconversion (Baddeley and Bewersdorf, 2018) 10–30 nm 30–60 nm High spatial resolution; temporal resolution is relatively worse Dani et al., 2010; Tang et al., 2016  
ExM Physical expansion of sample (Wassie et al., 2019) 4–20-fold improvement 4–20-fold improvement Capable of combining with other imaging techniques, only for fixed samples Gao et al., 2019; Sarkar et al., 2020 Preprint 
TechniquePrincipleResolutionCommentsApplications in spines and synapses
Lateral (XY)Axial (Z)
CLSM  250 nm 500 nm   
TPLSM Two-photon excitation 350 nm 700 nm Deeper tissue penetration; adaptive optics further improve Helmchen and Denk, 2005; Ji, 2017  
STED Stimulated emission (Vicidomini et al., 2018) 20–70 nm 500 nm 3-D STED increases axial resolution; chronic in vivo imaging is possible Nägerl et al., 2008; Berning et al., 2012; Pfeiffer et al., 2018  
SIM Moiré effect with structured illumination (Wu and Shroff, 2018) 100 nm 250 nm No need for special fluorophores; limited resolution improvement Kashiwagi et al., 2019; Li et al., 2020  
SMLM (PALM, STORM) Photoactivation, photoconversion (Baddeley and Bewersdorf, 2018) 10–30 nm 30–60 nm High spatial resolution; temporal resolution is relatively worse Dani et al., 2010; Tang et al., 2016  
ExM Physical expansion of sample (Wassie et al., 2019) 4–20-fold improvement 4–20-fold improvement Capable of combining with other imaging techniques, only for fixed samples Gao et al., 2019; Sarkar et al., 2020 Preprint 

CLSM, confocal laser scanning microscopy; SMLM, single-molecule localization microscopy; STORM, stochastic optical reconstruction microscopy; TPLSM, two-photon laser scanning microscopy.

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