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DCS induces an enhancement of visual flash response in
activation area and amplitude (single example). Left- and right-eye flash
responses are plotted in upper and lower rows, respectively (ipsilateral
responses are masked out). The color range is between mean + 1SD and the peak
value of the baseline visual evoked response. Areas exceeding 90% of the
baseline visual evoked response (active areas) are demarcated by solid black
borders. Credit: RIKEN
Researchers
at the RIKEN Brain Science Institute in Japan have discovered that the benefits
of stimulating the brain with direct current come from its effects on
astrocytes—not neurons—in the mouse brain. Published in Nature Communications,
the work shows that applying direct current to the head releases synchronized
waves of calcium from astrocytes that can reduce depressive symptoms and lead
to a general increase in neural plasticity—the ability of neuronal connections
to change when we try to learn or form memories.
Transcranial
direct current stimulation (tDCS) is a well-known and effective procedure that
has been used for decades to clinically treat major depression. The procedure
is non-invasive, lasts about 30 minutes, and involves targeting specific brain
areas by applying weak electric current through the head. In addition to
reducing symptoms of depression, it has even been shown to enhance learning and
synaptic plasticity in both humans and animals.
"While
we have known the clinical benefits of this kind of stimulation for quite some
time," notes team leader Hajime Hirase, "our research is aimed at
understanding the cellular mechanisms through which its effects are made
possible."
Because
calcium levels in astrocytes—a type of non-neural glial cell in the brain—have
recently been shown to be important for transmitting signals that help neurons
form connections with each other, Hirase and his team decided to examine brain
activity during transcranial direct current stimulation using calcium imaging.
To
accomplish this, they first made a transgenic mouse that expresses a fluorescent
calcium-indicator protein in astrocytes and a subset of neurons in the brain.
With this setup, they were able to image brain-wide calcium activity with a
standard fluorescence microscope.
When
they monitored calcium levels, they found that transcranial stimulation caused
large amplitude surges of calcium. "Surprisingly, the calcium surges
occurred very quickly after stimulation onset," explains lead author
Hiromu Monai, "and appeared synchronized all over the cortex not only near
the stimulated location."
The
calcium surges were absent when the same experiment was performed on mice in
which rising calcium levels in astrocytes were prevented, either through
knocking out a key receptor or by pharmacologically blocking another one. This
allowed the researchers to know that astrocytes, not neurons, were the source
of the waves. This was confirmed when they expressed the fluorescent marker
using two different recombinant adeno-associated viruses, allowing them to
distinguish calcium in neurons from calcium in astrocytes.
Next,
they examined the importance of the calcium surges using a mouse model for
stress-induced depression. While transcranial stimulation can normally reduce
depression-like behavior in these mice, it failed when they blocked the
astrocytic calcium surges. "This suggests that the positive effects of
transcranial direct current stimulation on depression lie in these wide-spread
calcium surges," says Monai. "But, we also wanted to investigate
their effects on neural plasticity in general."
To
examine this role of astrocytic calcium surges, the team looked at changes in
sensory responses after transcranial stimulation. They measured the responses
to flashes of light and whisker perturbation, and found that they were more
than 50% greater after stimulation—an effect that lasted for 2 hours after
stimulation was over. These plastic changes in neuronal responses disappeared
when calcium surges in astrocytes were prevented, indicating their importance
in helping to change the connectivity between neurons.
"That
this mechanism is mediated by astrocytic activity is exciting and hints that
astrocytes could be a major therapeutic target for neuropsychiatric
diseases," notes Hirase. "Additionally, glial activation by
transcranial direct current stimulation should be carefully examined in
primates (including humans), and perhaps safety standards should to be
re-evaluated from the standpoint of glia."
More
information: Monai H, Ohkura M, Tanaka M, Oe Y, Konno A, Hirai H, Mikoshiba K,
Itohara S, Nakai J, Iwai U, Hirase H. (2016) Calcium imaging reveals glial
involvement in transcranial direct current stimulation-induced plasticity in
mouse brain. Nature Communications DOI: 10.1038/ncomms11100
Journal
reference: Nature Communications search and more info website
Provided
by: RIKEN
Source: http://medicalxpress.com
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