In retinitis pigmentosa – a degenerative disease which often leads to incurable blindness- the loss of photoreceptors deprives the retina from a continuous excitatory input, the so-called dark current. In rodent models of this disease this deprivation leads to oscillatory electrical activity in the remaining circuitry, which is reflected in the rhythmic spiking of retinal ganglion cells (RGCs). It remained unclear, however, if the rhythmic RGC activity is attributed to circuit alterations occurring during photoreceptor degeneration or if rhythmic activity is an intrinsic property of healthy retinal circuitry which is masked by the photoreceptor’s dark current. Here we tested these hypotheses by inducing and analysing oscillatory activity in adult healthy (C57/Bl6) and blind mouse retinas (rd10 and rd1). Rhythmic RGC activity in healthy retinas was detected upon partial photoreceptor bleaching using an extracellular high-density multi-transistor-array. The mean fundamental spiking frequency in bleached retinas was 4.3 Hz; close to the RGC rhythm detected in blind rd10 mouse retinas (6.5 Hz). Crosscorrelation analysis of neighbouring wild-type and rd10 RGCs (separation distance <200 µm) reveals synchrony among homologous RGC types and a constant phase shift (∼70 msec) among heterologous cell types (ON versus OFF). The rhythmic RGC spiking in these retinas is driven by a network of presynaptic neurons. The inhibition of glutamatergic ganglion cell input or the inhibition of gap junctional coupling abolished the rhythmic pattern. In rd10 and rd1 retinas the presynaptic network leads to local field potentials, whereas in bleached retinas additional pharmacological disinhibition is required to achieve detectable field potentials. Our results demonstrate that photoreceptor bleaching unmasks oscillatory activity in healthy retinas which shares many features with the functional phenotype detected in rd10 retinas. The quantitative physiological differences advance the understanding of the degeneration process and may guide future rescue strategies.

recently membrane currents from skeletal myotubes, [7] from glia or from glia-derived cancerogenic glioma cells [8] or from pancreatic beta cells [9] have been reported. In brain or muscle tissues different cell types interact. As a consequence the generated electrical signals comprise a rich frequency content ranging from few Hertz to several kilohertz. [10] Electrical signaling on sub-millisecond time scale occurs during so-called action potentials, when the transmembrane potential changes rapidly due to the opening and closing of voltagegated sodium channels.In this review we will discuss biotechnological aspects relevant for the "electrical imaging" technique and highlight applications in neuroscience. Related recent reviews discussed some of the technological backgrounds of microelectrode arrays [11] and some of their applications. [6] To estimate the requirements needed to image the electrical activity in neurons and networks, we summarize important scales and numbers. A typical neuron comprises a cell body, which integrates the presynaptic signals using an elaborate dendritic network (dendritic tree) and sends an action potential (stereotyped transmembrane voltage signal) activity to synaptically connected neurons using a thin axonal cable-like fiber. Mammalian cell bodies are typically about 10-20 µm in diameter, while the cable-like dendritic and axonal structures have diameters ranging between a few tens of nanometers up to several micrometers. [12] The entire dendritic tree of one neuron or of a synaptically connected neuronal network may cover an area ranging between few tens of micrometers up to tens of square millimeter. [12] Within the retinal ganglion cell layer or hippocampal cell layers the neuronal density may be as high as 5000-10 000 cells mm −2 (mouse retinal ganglion cells, [13] granule cells), [14] to name just two prominent neural tissues studied so far using electrical imaging. These numbers highlight the spatial range and resolution to be achieved for imaging the electrically activity generated and propagating therein at (sub) cellular resolution.Optical imaging-the most common imaging modality in life sciences-achieves high-resolution digital imaging by magnifying and recording the light signal using a complementary metal-oxide semiconductor (CMOS) camera chip. Relevant parameters for optical imaging comprise (i) a large field of view, (ii) a high signal-to-noise ratio (SNR), and (iii) high spatial and (iv) high temporal resolution. The ratio between the sensitivity of the CMOS sensors (i.e., minimal number of detected photons) and the corresponding pixel noise sets the sensitivity limit.Electrical imaging-potentially a complementary or alternative technique of optical imaging-deals with the same constrains. Here, instead of a light-detecting CMOS camera chip, the changing Electrical imaging of extracellular potentials reveals the activity of electrogenic cells and of networks thereof over several orders of magnitude, both in space and time. On a spatial scale, electrical activity pro...

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