Biomedical Engineering Reference
In-Depth Information
in LFP amplitude within 1 s, occurred at 10 Hz stimulation.
Accordingly, 10 Hz whisker stimulation did not trigger astro-
cytic Ca
2
+
responses
(9)
. Additional experiments using 3 and 7
Hz whisker stimulation confirmed that astrocytic Ca
2
+
responses
peaked at 5 Hz and decreased at both lower and higher frequen-
cies (
Fig. 5.3C
). Since astrocytic Ca
2
+
signaling was delayed by
∼
3 s compared with neuronal field potential signals, there must
be an accumulating effect of neuronal activity on the astrocytic
Ca
2
+
elevations. To test the idea that astrocytic Ca
2
+
increases
are a function of the intensity of local synaptic input, we calcu-
lated the summed LFP amplitude during the first 9 s of stimu-
lation. As an index of total neuronal activity within a given time
window, the sum of LFPs has also been widely used to positively
correlate neuronal activity with cerebral blood flow (CBF)
(21)
.
Notably, the summed LFP amplitudes peaked at 5 Hz during the
first 9 s of stimulation (
Fig. 5.3D
) and had a strong correlation
with astrocyte somatic Ca
2
+
signaling (R
2
=
0.68, P
<
0.001;
Fig. 5.3E
)
6. Implications for
BOLD Signaling
The basis for a positive BOLD signal is the increase in blood flow
and volume that occur during neural activity. As discussed above,
new development has shown that astrocytes can mediate func-
tional hyperemia by release of vasoactive agents, indicating that
astrocytic Ca
2
+
signaling may be both necessary and sufficient for
changes in the BOLD signal
(10, 17-19, 51)
. The initial studies
on astrocytic control of the microvasculature were performed in
slice preparations. One line of work showed that astrocytic Ca
2
+
increases are linked to activation of Ca
2
+
- sensitive phospholipase
A2 (PLA2), which, in turn, stimulate the production of arachi-
donic acid (AA). Several AA metabolites are powerful vasoactive
compounds. For example, the products of cyclooxygenase (COX)
induced vessel dilation in both brain slice and in vivo prepa-
rations
(10)
. Furthermore, the cytochrome P450 epoxygenase
pathway produces epoxyeicosatrienoic acids (EETs), which medi-
ated vessel dilation in retina
(18)
, whereas astrocytic Ca
2
+
signal-
ing triggered vessel dilation through activation of Ca
2
+
-sensitive
K
+
channels in the astrocyte endfeet in cortical slices
(19)
.In
addition, two lines of work have suggested that astrocytic Ca
2
+
signaling in both retina and acute hippocampal slices is linked
to production of the vasoconstrictor 20-hydroxyeicosatetraenoic
acid, 20-HETE
(17, 18)
(
Fig. 5.1
). However, a major drawback
of studying blood flow regulation in ex vivo preparation is the
loss of pressure-induced vasculature tone. Our in vivo experi-
ments, employing targeted photolysis of caged Ca
2
+
in astrocytic
6.1. Astrocytic Ca
2
+
Elevations Contribute
to Cerebral Blood
Flow Regulation
