Imaging plasticity and structure of cortical maps in cat and mouse visual cortex

The study reported in the first part of this thesis utilized
optical imaging of intrinsic signals to visualize changes in
orientation maps in cat visual cortex induced by pairing a visual
stimulus with an intracortical electrical stimulation. We found
that the direction of plasticity within orientation maps depends
critically on the relative timing between visual and electrical
stimulation on a millisecond time scale: a shift in orientation
preference towards the paired orientation was observed if the
cortex was first visually and then electrically stimulated. In
contrast, the cortical response to the paired orientation was
diminished if the electrical preceded the visual cortical
stimulation. Spike-time-dependent plasticity has been observed in
single cell studies; however, our results demonstrate an analogous
effect at the systems level in the live animal. Thus,
timing-dependent plasticity needs to be incorporated into our
conception of cortical map development. While the pairing paradigm
induced pronounced shifts in orientation preference, the general
setup of the orientation preference map remained unaltered. In
order to unravel potential factors contributing to this overall
stability, we determined the distribution of plasticity across the
cortical surface. We found that pinwheel centers, points were
domains of all orientation meet, exhibited less plasticity than
other regions of the orientation map. The resistance of pinwheel
centers to changes in orientation preference may support
maintenance of the general structure of the orientation map. The
study that forms the second part employs optical imaging to
visualize the retinotopy in mouse visual cortex. We were able to
resolve the pattern of retinotopic activity with high precision and
reliability in the primary visual cortex (area 17). Functional
imaging of the position, size and shape of area 17 corresponded
exactly to the location of this area in stained histological
sections. The imaged maps were also confirmed with
electrophysiological recordings. The retinotopic structure of area
17 showed very low inter-animal variability, thus allowing
averaging maps across animals and therefore statistical analysis.
These averaged maps greatly facilitated the identification of at
least four extrastriate visual areas. In addition, we detected
decreases in the intrinsic signal below baseline with a shape and
location reminiscent of lateral inhibition. This decrease of the
intrinsic signal was shown to be correlated with a decrease in
neuronal firing rate below baseline. Both studies were facilitated
by the development of a signal analysis technique (part III), which
improves the quality of optical imaging data. Intrinsic signal
fluctuations originating from blood vessels were minimized based on
their correlation with the actual superficial blood vessel pattern.
These fluctuation components were then extracted from images
obtained during sensory stimulation. This method increases the
reproducibility of functional maps from cat, rat, and mouse visual
cortex significantly and might also be applied to high resolution
imaging using voltage sensitve dyes or functional magnetic
resonance.