Title:Relevance of Excitable Media Theory and Retinal Spreading Depression Experiments in Preclinical Pharmacological Research
Volume: 12
Issue: 5
Author(s): V.M. Fernandes de Lima and W. Hanke
Affiliation:
Keywords:
Chicken retina, excitable media, preclinical pharmacology, spreading depression.
Abstract: In preclinical neuropharmacological research, molecular, cell-based, and systems using animals are well
established. On the tissue level the situation is less comfortable, although during the last decades some effort went into
establishing such systems, i.e. using slices of the vertebrate brain together with optical and electrophysiological
techniques. However, these methods are neither fast, nor can they be automated or upscaled. By contrast, the chicken
retina can be used as a suitable model. It is easy accessible and can be kept alive in vitro for hours up to days. Due to its
structure, in addition the retina displays remarkable intrinsic optical signals, which can be easily used in experiments.
Also to electrophysiological methods the retina is well accessible.
In excitable tissue, to which the brain and the retina belong, propagating excitation waves can be expected, and the
spreading depression is such a phenomenon. It has been first observed in the forties of the last century. Later, Martins-
Ferreira established it in the chicken retina (retinal spreading depression or RSD). The electrophysiological characteristics
of it are identical with those of the cortical SD. The metabolic differences are known and can be taken into account. The
experimental advantage of the RSD compared to the cortical SD is the pronounced intrinsic optical signal (IOS)
associated with the travelling wave. This is due to the maximum transparency of retinal tissue in the functional state; thus
any physiological event will change it markedly and therefore can be easily seen even by naked eye. The theory can
explain wave spread in one (action potentials), two (RSDs) and three dimensions (one heart beat).
In this review we present the experimental and the excitable media context for the data interpretation using as example the
cholinergic pharmacology in relation to functional syndromes. We also discuss the intrinsic optical signal and how to use it in pre-clinical research.
