Cell volume changes are associated with alterations of intrinsic optical si
gnals (IOS). In submerged brain slices in vitro, afferent stimulation induc
es an increase in light transmission. As assessed by measurement of the lar
gely membrane impermeant ion tetramethylammonium (TMA) in the extracellular
space, these IOS correlate with the extent and time course of the change o
f the extracellular space size. They have a high signal to noise ratio and
allow measurements of IOS changes in the order of a few percent. Under cond
itions of reduced net KCl uptake (low Cl solution) a directed spatial buffe
r mechanism (K syphoning) can be demonstrated in the neocortex with widenin
g of the extracellular space in superficial layers associated with a reduce
d light transmission and an increase of extracellular K concentration. The
nature of the IOS under pathophysiological conditions is less clear. Spread
ing depressions first cause an increase of light transmission, then a decre
ase. Such a decrease has also been observed following application of NMDA w
here it was associated with structural damage. Pharmacological analyses sug
gest that under physiological conditions changes of extracellular space siz
e are mainly caused by astrocytic volume changes while with strong stimuli
and under pathophysiological conditions also neuronal swelling occurs. With
reflected light usually signals opposite to those observed with transmitte
d light are seen. Recording of IOS from interface slices gives very complex
signals since under these conditions an increase of light transmission has
been reported to be superimposed by a decrease of the signal due to mechan
ical lensing effects of the slice surface. Depending on the method of measu
rement and the exact conditions, several mechanisms may contribute to IOS.
Under well defined conditions IOS are a useful supplementary tool to monito
r changes of extracellular volume both in space and time.