eBook: Advancing Neuroscience Research - 7

Imaging the brain with
super resolution
Super-resolution microscopy, so named for its ability
to resolve structures smaller than the traditional
imaging barrier of the diffraction limit, has developed
quickly in recent years. One of these methods,
structured illumination microcopy (SIM), uses
a spatially structured pattern of light to excite the
sample, and a super-resolution image is computationally
reconstructed from the resulting interference
patterns. SIM platforms are quickly evolving
to become more powerful and easier to use than
their predecessors; Nikon's N-SIM S Super Resolution
Microscope is fast enough for super-resolution
imaging of live cells.
A recent study led by Satoshi Gojo at the Kyoto Prefectural
University of Medicine used Nikon's N-SIM
S system to localize exogenous mitochondrial DNA
within endogenous mitochondria.5
Such a feat-
finding specific DNA inside a subcellular organelle-was
made feasible using super-resolution
microscopy. " Mitochondrial dysfunction is at play
in many disorders, including some forms of neurodegeneration,
so I look forward to seeing where
this discovery leads, " says Adam White, Product
and Logistics Manager in Advanced Microscopy at
Nikon Instruments.
Combining Nikon's N-SIM with optogenetics allowed
Kai Zhang's group at the University of Illinois
at Urbana-Champaign to explore finer details of
the nerve growth factor (NGF) receptor signaling
pathway.6
Normally, NGF activates tyrosine kinase
A (TrkA) as well as another lower-affinity receptor.
Zhang's group used optogenetics-originally developed
to modulate neuronal activity with light
and genetic modifications-to zero in on TrkA activation
alone, with the aim of precluding off-target
effects that can occur when using NGF to study TrkA-mediated
events. They used SIM to confirm dimerization
of the optogenetic TrkA receptors in response
to blue light stimulation, and suggest that
their method be used to study the mechanisms
of other receptor-mediated signaling pathways. " I
find this an interesting application for optogenetics,
as it demonstrates how these tools can augment
more traditional methods for studying cell
signaling, " says White.
7
eBook: Advancing Neuroscience Research

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