Biomedical Engineering Reference
In-Depth Information
of adequate smooth muscle resting tone, the disruption of cel-
lular networks, the use of abnormal glucose and oxygen levels,
issues that certainly affect neurovascular coupling. Therefore, in
vitro results require to be validated in vivo with the same temporal
and spatial resolution, a challenge that can now be achieved using
new imaging tools. We describe here the advantages of combining
two-photon laser scanning microscopy and well defined neuronal
networks such as olfactory bulb glomeruli, in order to investigate
the role of postsynaptic neuronal activation in triggering vascular
responses.
2. The Glomerular
Module as a
Model to Study
Neurovascular
Coupling
Deciphering the nature of neurovascular coupling in the brain
requires the choice of a region with the following properties:
It should be activated with physiological stimuli, its anatomi-
cal organization should allow to determine which cell type and
number are activated upon stimulation as well as which capillaries
supply the activated cells. Under these conditions, one can realis-
tically envisage to understand the entire chain of events that links
transmitter release to local cerebral blood flow (CBF) changes. At
first glance, the rodent olfactory bulb seems to be an ideal model.
As the cortex, it is a dorsal region easily accessible to imaging and
electrophysiological recordings. Because of its anatomical organi-
zation, it is functionally organized in modules: Olfactory receptor
neurons (ORN), expressing a given odorant receptor type, send
their axons to the bulb where they converge onto only 2 topo-
graphically fixed glomeruli
(21, 22)
, each one located on one side
of a plane of symmetry that separates each bulb in two
(23)
. Thus,
at low concentration, one may expect an odorant to activate only
2 distant “symmetric” glomeruli and 2 different odorants to acti-
vate different glomeruli (
see
Fig. 4.1)
. However, several imag-
ing methods have revealed that odorants activate small glomeruli
ensembles. These methods include: (i) Blood oxygenation level
dependent functional MRI
(24-27)
, (ii) Optical imaging of cal-
cium
(28-30)
voltage
(31)
and intrinsic signals
(32-37)
, (iii)
Electrophysiological recordings
(38-40)
,(iv)Measurementsof2-
deoxyglucose consumption
(41, 42)
. Thus, if diluting odorants
does reduce the number of activated glomeruli, the limitation of
odorant receptor specificity, the nature of the signals detected as
well as the detection thresholds of these methods do not allow to
ensure that only the 2 “symmetric” glomeruli are activated in an
olfactory bulb. Still, this region remains a good model to study
neurovascular coupling for several other reasons: (i) It is the first
relay of olfaction in the central nervous system and, as such, it is
weakly influenced by anesthesia in comparison to cortical areas.
