26 September 2001. In a feat of miniaturization, researchers have engineered a
fluorescence microscope that is three inches long, weighs less than an ounce,
and sits perched on a rat's head. Fritjof Helmchen, Winfried Denk, and colleagues
at Bell Laboratories in Murray Hill, New Jersey, report in tomorrow's Neuron that
their camera can image cortical neurons with subcellular resolution in freely
Previous research has used similar technology to visualize blood vessels, neuronal
dendrites-even amyloid deposition-in anesthetized mice that were mounted onto
a fixed two- or multiphoton microscope (Svoboda
K et al.M, Kimchi,
EY et al.). This work pushes the technological envelope by fitting all the
necessary technology into a tiny device that awake, behaving rats can carry
around while moving about the cage.
Dubbed fiberscope, the device is tethered to a pulsed laser by an optical fiber
that carries both the excitation light to the brain and the output signal back
to a computer housing control panels and imaging software. Attached surgically
to the rat's head, the fiberscope has a tiny, motor-driven objective that focuses
the incoming light into the neocortex and a fiber tip that scans the imaged
area by a resonance vibration mechanism.
The fiberscope can image blood vessels, capillaries, blood cell movements,
and dendrites, though its depth penetration and resolution cannot yet match
that of the fixed two-photon microscope, the authors report. The image remained
stable while the rats rested and chewed, and fairly stable while they turned
and walked steadily. Sudden jerks of the head, however, disturbed the image
for a while before it stabilized again.
The present prototype fiberscope should be improved, the scientists write,
by making it even smaller so a mouse can carry it. Moreover, the technology
currently is limited by the need to label individual neurons with micropipettes
and then having to search for those dye-filled cells. It will soon be possible,
however, to label populations of cells with genetically encoded functional probes
expressing green fluorescent protein, the authors write.
For now, immediate applications for this technology lie in the area of studying
dendritic integration of synaptic inputs, and how dendritic activity changes
during sleep, wakefulness, and other behavioral states. In the future, Alzheimer's
researchers might want to image plaque or tangle formation, or dendritic activity
in animal models of this disease.-Gabrielle Strobel.
Reference:Helmchen F, Fee MS, Tank DW, Denk W. A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals. Neuron. 2001 Sep 27;31(6):903-12. Abstract
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