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12 August 2009
The human brain contains billions of neurons,
and these are organised into thousands of
distinct groups. For researchers, knowing
the exact function of each type of neuron
would be invaluable, as it would help them
to find the root of many diseases and develop
effective treatments.
Currently, scientists must gain their knowledge
of neuron function by correlating brain
activity with certain behaviors, for example
linking a damaged area of the brain to a
particular loss of function. They can also
activate certain areas of the brain and
study the resulting behaviour, but the methods
available to do this are invasive, which
greatly limits their use.
Investigators at Duke University and the University of North Carolina (UNC), US, have now developed a non-invasive technique that could potentially allow neuroscientists to discover the function of any population of neurons in an animal brain.
In a previous study, Dr Bryan Roth, at
UNC, explored his idea to create a cell
receptor that could somehow be incorporated
into neurons, and which could only be activated
by a specific inert drug. This receptor
would act as a type of switch, activating
a particular set of neurons in the brain.
Using yeast genetics, Roth and his team
managed to create a receptor that could
interact with a specific chemical. This
was possible because yeast can reproduce
and evolve very quickly.
The group set out to create a similar receptor
in animal models. In their first attempt
to breed animals possessing the receptor,
they decided to target the neurons of the
hippocampus and cortex. The receptor was
designed to be activated by a drug called
clozapine-N-oxide (CNO), which had no other
effects on the animals, nor upon the neurons
that did not contain the receptor.
Interestingly, when the animals were injected
with CNO, they started to experience seizures.
The researchers had created a model for
studying epilepsy.
For the current study, Dr Roth collaborated
with epilepsy expert Dr James McNamara,
at Duke University. Their team discovered
a method of selectively activating certain
sets of neurons, using controlled administration
of CNO. In this way they were able to examine
neuronal activity before and during seizures.
Dr McNamara commented "Elaborating
on this method promises to let scientists
engineer different kinds of mutant models
in which single groups of neurons will be
activated by this chemical, so scientists
can understand the behaviors mediated by
each of these groups."
For epilepsy, the discovery of this method
is extremely exciting. The knowledge gained
from its future implementation could lead
to better treatments for humans, which target
only the precise neurons responsible for
seizure development, and cause fewer side-effects.
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