光基因技术实现单个神经元的开闭

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moomoofarm

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May 13, 2009, 8:51:35 AM5/13/09
to Neurosociety
Laser-Controlled Humans Closer to Reality

  MIT的Boyden通过经基因工程处理的病毒感染特定位置神经元的某个离子通道让其开启,然后通过激光影响该神经元让其放电从而影响其他神经
元。

  这个研究还是非常厉害的。但是只能影响特定的细胞,未免有点可惜。而且病毒是怎么定向地影响神经元某个位置呢?毕竟我以为就算是经过基因工程处理,
一旦进入体内(且不论它是如何进入的)在定位上仍然还是比较困难的,该文并没有提及怎么送到特定的神经元(以及神经元的某个离子通道)的问题。

  Flashes of light may one day be used to control the human brain, and
that day just got a lot closer.

  Using lasers, researchers at the MIT Media Lab were able to activate
a specific set of neurons in a monkey’s brain. Though the technique
has been used to control and explore neural circuits in fish, flies
and rodents, this is the first time the much-hyped technology has ever
been used in primates.

  “It paves the way for new therapies that could target a number of
psychiatric disorders,” said MIT neuroscientist Ed Boyden, who led the
research with postdoctoral fellow Xue Han. “This is very exciting from
a translational standpoint.”

  The beauty of this optogenetic technique is its specificity. By
using a combination of lasers and genetic engineering, scientists can
control, to the millisecond, the firing of a specific class of
neurons, allowing them to pinpoint problematic cells and circuits
while leaving innocent bystanders alone, thus minimizing potential
side effects.

  Viruses are engineered to infect neurons with a special type of
channel, originally discovered in algae, which is sensitive to blue
light. Once a blue laser shines on the infected neurons, the channels
snap open, ions rush into the cell, and the neuron fires.

  Crucial to the technique is that the virus is only injected into a
very small part of the brain, and only a certain class of neurons,
once infected, actually turn the channel on. The sharp laser beam
further zeros in on a small portion of the brain. This precise aim is
in contrast to current techniques, such as drugs and electrodes, both
of which have a much broader reach.

  The optogenetic method was pioneered in 2005 by Boyden and Karl
Deisseroth at Stanford University and has since been used to
understand how circuits of neurons control various behaviors, such as
learning in mice and predator escape in fish. But until now,
scientists had never demonstrated the technique in primates — a move
essential for developing therapeutic uses for the technology in
humans.

  Boyden’s new research, published Wednesday in Neuron, demonstrates
not only that the technology works in primates, but also that it is
safe. The rhesus macaques received multiple rounds of injections and
laser stimulations over the course of eight or nine months without
damaging the neurons or activating the brain’s immune system, an
obvious concern when viruses are involved.

  “Many disorders are associated with changes in specific cell types,”
said Boyden. “For therapeutic purposes, you want to affect certain
cells, but you want to leave normal cells intact. The ability to use
light to turn specific cells on and off with very precise timing could
in principle allow new therapies.”

  Future applications could involve using light-emitting neural
prosthetics to replace the electrodes used in deep brain stimulation,
which currently activate or silence a broad range of neurons. Deep
brain stimulation has shown promise in treatments of Parkinson’s
disease, epilepsy and depression, but it has a number of side effects,
stemming in part from its lack of specificity.

  “Our ability to remedy problems in the brain may ultimately be
limited by how many side effects occur,” said Boyden. “We could find
ways to shut down seizures but the side effects might be intolerable.
By pinpointing specific cell types, we could craft therapeutic
neuromodulators and directly develop therapies, while preserving a
high degree of well-being.”

  Proving the method works in primate brains paves the way not only
for cleaner therapies, but also for understanding the relationship
between specific neural circuits and behaviors, particularly higher
cognitive functions.

  Genetically, mice are ideal model organisms — but their behavioral
repertoire isn’t very sophisticated. If neuroscientists hope to
understand and treat problems like ADHD, schizophrenia, depression and
compulsive behaviors like addiction, they can run far-more-powerful
experiments using primates.

  “This is a very important and exciting step forward for all systems
neuroscience,” said a neuroscientist who preferred to remain anonymous
due to recent attacks against primate researchers.

  “There are many limitations with the current way we try to
understand neural circuits, primarily the lack of specificity. The
hope is that as this sort of research continues in labs around the
world, it will become possible to specifically target many different
classes of neurons. We can learn how each of them contributes to
specific cognitive functions.”

  Citation: “Millisecond-Timescale Optical Control of Neural Dynamics
in the Nonhuman Primate Brain,” by Xue Han, Xiaofeng Qian, Jacob G.
Bernstein, Hui-hui Zhou, Giovanni Talei Franzesi, Patrick Stern,
Roderick T. Bronson, Ann M. Graybiel, Robert Desimone and Edward S.
Boyden. Neuron 62, 191–198, April 30, 2009.
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