  Imaging neuronal activity non-invasively in vivo is of tremendous interest,
but current imaging techniques lack either functional contrast or necessary
microscopic resolution. The retina is the only part of the central nervous
system (CNS) that allows us direct optical access. Not only ophthalmic
diseases, but also many degenerative disorders of the CNS go along with
pathological changes in the retina. Consequently, functional analysis of
retinal neurons could lead to an earlier and better diagnosis and understanding
of those diseases. Recently, we showed that an activation of photoreceptor
cells could be visualized in humans using a phase sensitive evaluation of
optical coherence tomography data. The optical path length of the outer
segments changes by a few hundred nanometers in response to optical
stimulation. Here, we show simultaneous imaging of the activation of
photoreceptor and ganglion cells. The signals from the ganglion cells are
ten-fold smaller than those from the photoreceptor cells and were only visible
using new algorithms for suppressing motion artifacts. This allowed us to
generate a wiring diagram showing functional connections between photoreceptors
and ganglion cells. We present a theoretical model that explains the observed
intrinsic optical signals by osmotic volume changes, induced by ion influx or
efflux. Since all neuronal activity is associated with ion fluxes, imaging
osmotic induced size changes with nanometer precision should visualize
activation in any neuron.
