Biomedical Engineering Reference
In-Depth Information
modulate neuronal cytosolic Ca
2
+
, large spike-like increases in
neuronal Ca
2
+
levels, suggesting that astrocytes participate more
directly in neurotransmission than previously recognized
(2, 3)
.
Bidirectional communication between neurons and astrocytes
was later demonstrated in acute brain slices
(4-7)
and the isolated
retina preparation
(8)
. Although bidirectional communication
has been studied for more than a decade, it was first recently
demonstrated that astrocytes are activated during sensory stimu-
lation in vivo
(9)
. This was an important step, because activation
of astrocytes in previous ex vivo experiments often required exces-
sive stimulation, including high intensity electrical stimulation
(10)
, mechanical distortion
(11)
, traumatic injury
(12)
, agonist
application
(13)
and laser light
(14)
. Understanding the role of
astrocytic Ca
2
+
signaling in the intact brain has direct implication
for functional brain imaging, since new lines of evidence suggest
that astrocytes play a key role in functional hyperemia (reviewed
in
(15)
). The basis of blood oxygen level dependent (BOLD)
functional magnetic resonance imaging (fMRI), and positron
emission tomography (PET) functional imaging, as well as
intrinsic signal optical imaging, is that neural activity is coupled
to increases in local blood flow
(16)
. However, the mechanisms
linking neuronal activity to increases in local perfusion remain
poorly understood. Since the first description by Golgi at the end
of 1800s that astrocytic endfeet contact arterioles and capillaries
in the brain, it has been speculated that astrocytes have the poten-
tial to modulate the cerebral blood flow. Indeed, several in vitro
studies highlighted the importance of neuron-to-glia signaling
in vessel diameter
(10, 17-20)
. Although different mechanisms
have been proposed for the function of astrocytes in control
of microcirculation, a common conclusion is that elevations in
astrocytic cytosolic Ca
2
+
levels are necessary and sufficient to
cause changes in the diameter of arterioles. Yet, an essential
question to be addressed is whether these astrocytic Ca
2
+
transients occur in vivo during physiological neural activation.
We have, in recent work, addressed the signaling pathway
from neurons to astrocytes in live adult mice using 2-photon laser
scanning microscopy. We analyzed changes in neuronal local field
potentials (LFPs) and astrocytic Ca
2
+
signaling evoked by whisker
stimulation in barrel cortex layer 2 of adult mice. We found that
whisker stimulation promptly evoked astrocytic Ca
2
+
responses in
vivo. The slow onset (
20 s) of the
astrocytic Ca
2
+
signaling compared with the properties of LFPs
suggested that temporal summation of electrical events with a
long time constant determined the development of the astrocytic
Ca
2
+
elevation. We found that the changes of astrocytic Ca
2
+
sig-
naling were a direct function of the summated LFPs amplitude,
which was commonly used to predict the amplitude of increases in
cerebral blood flow changes during sensory stimulation
(21, 22)
.
∼
3 s) and long time course (
∼
