Storage of information in cultured neurons

Photo Sharing and Video Hosting at PhotobucketCultured neurons seem like ants away from their colony: removed from their parent organ, dissociated from their fellow workers and placed into an unnatural environment. But neurons plated onto a culture dish connect to each other, forming simple neural networks that give rise to spontaneous electrical activity. And, in recent years, researchers have developed culture dishes containing arrays of microelectrodes embedded within them, such that the electrical activity of the cultured neurons can be recorded. These new techniques have revealed the remarkable functional properties of neurons in culture – the cultured networks of dissociated cells can “learn”. In other words, they can modify their initially spontaneous activity into something purposeful, such as controlling a flight simulator or controlling the movements of artificial animals in a virtual environment.

Now, Itay Baruchi and Eshel Ben-Jacob of Tel Aviv University show that networks of cultured neurons can also store information. The image on the left shows their experimental set up. Nerve cells were isolated and cultured on a specialized dish in which microelectrodes are embedded so that the electrical activity of the cells can be recorded. A micropipette was then used to apply picrotoxin to small groups of cells in specific locations on the culture dish. Picrotoxin is a GABA receptor antagonist; its addition to the culture dish therefore suppressed the activity of inhibitory interneurons in the cell culture. As a result, synchronized bursting events (SBEs) – waves of electrical activity with specific patterns in both space and time – were observed in the nerve cell culture.

The cultured neurons “stored” information about the patterns of electrical activity evoked in the network by application of picrotoxin. Several different types of SBEs were evoked in the network, each of which starts at a specific location in the culture dish and is propagated along a specific trajectory. This activity continued as long as picrotoxin was applied; when the drug was removed, the cultured cells returned to their basal activity. But the SBEs could be precisely reproduced later on. If the initial application of picrotoxin to a specified location on the culture dish generated a specific type of SBE, exactly the same pattern of activity could be elicited up to 40 hours later by applying picrotoxin to the same location. Thus, the collective activity of the cultured cells had somehow been “imprinted” within the network.


Baruchi, I. & Ben-Jacob, E. (2007). Towards neuro-memory-chip: Imprinting multiple memories in cultured neural networks. Phys. Rev. E. doi: 10.1103/PhysRevE.75.050901. [Full text]


Müller cells: Nature’s fibre optics

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“Schematic representation of mammalian retina structure. Artistic grouping of cells and direction of current flow.” A, layer of rods and cones; B, visual cell body layer; C, outer plexiform layer; D, bipolar cell layer; E, inner plexiform layer; F, layer of ganglion cells; G, optic nerve fibre layer; L, central fossa. Modified from a photograph taken from the original (22×33 cm). Drawn on sheet/ paper.
P. Y. 1901. Cajal Institute – CSIS – Madrid, Spain.

This diagram by Santiago Ramón y Cajal shows the neural circuitry of the vertebrate retina. The retina’s inverted structure seems ill-suited to its function: the rods and cones (labelled A, a and b in the diagram) are the photosensitive cells that transduce light energy into electrical impulses; they point away from incoming light, and are located at the back of the retina, so that light entering the eye has to pass through several layers of randomly oriented and irregularly organized cells before it reaches them. The retina also contains nerve fibres that are positioned perpendicular to the path of light entering the eye, and many of the structures in the upper layers have a diameter similar to that of the wavelength of visible light. Because of this inversion, one would think that incident light entering the eye should be subjected to a significant amount of reflection and scattering. Yet, nature somehow contrived to overcome this awkward architecture, and the retina performs its function perfectly.

As well as the various types of neurons, the retina contains specialized glial cells called Müller cells, which are arranged in parallel to each other and are oriented in the direction along which light travels through the eye. Müller cells are about 150 µm (micrometres, thousandths of a millimetre) in length, and span the entire thickness of the retina, projecting from the vitreous humour (the viscous fluid in the back of the eye) to the back of the retina where light enters the rods and cones. Müller cells have, like other glial cells, been largely ignored until recently: they were thought to do little more than support and nourish retinal neurons. (Notice that Cajal’s diagram does not show Müller cells.) But in recent years it has been determined that glial cells perform other important functions, and now, new research, published online in the Proceedings of the National Academy of Sciences, shows that glial cells may also be nature’s solution to the inverted retina problem. The new study, led by Jochen Guck of Cambridge University and Andreas Reichenbach of the Paul-Flechsig Institute of Brain Research at the Universität Leipzig in Germany, provides evidence that Müller cells function as optical fibres that transmit light through the retina.

Guck and his colleagues dissected guinea pig retinae, placed them under a confocal scanning microscope, and used a light source to mimic the natural illumination to which the tissues would be exposed. They then scanned the back of the tissues to determine the patterns produced there by light entering the tissue. To their surprise, the images they obtained contained a regular pattern of bright spots which alternated with darker areas on which there was less light. Retinae from rabbits and humans showed the same reflection pattern. Serial sections were then cut from the back of the retina. The dark spots they had observed were found to be 2-3 µm in diameter and spaced 5-6 µm apart. When the sections were reconstructed, it was found that the dark spots formed tubular structures that ran the entire thickness of the retina, and that they had funnel-shaped structures with a diameter of approximately 15 µm at one end. The extent of back-scattering (that is, the scattering of light in the direction from which it came) in the different regions of the back of the retina was then examined. This showed that there was significant back-scattering in cell layers near the photoreceptors, but very little in the dark spots, indicating that the tube-like structures within the dark spots transmit far greater amounts of light than the surrounding tissues. The arrangement of tube-like structures was also found to correspond well to the size and spacing of Müller cells.

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Fluorescence microscopic image of the retina, showing Müller cells stained red (left, kindly provided by Professor Andreas Reichenbach) and individual Müller cells in the dual beam laser trap (right).

The researchers then investigated the optical properties of the Müller cells. Guinea pig retinae were treated with enzymes that cause the cells in the tissue to dissociate from one another. A dual beam laser trap was then used to investigate the ability of Müller cells to propagate light. (Like optical tweezers, laser trapping is a technique by which beams of light are used to keep particles or cells in a fixed position.) Individual cells floating in a suspension were aligned between the ends of two optic fibres. One of the fibres could be used to shine light onto the cells; the other was connected to a power meter. By bringing the fibres into contact with a free-floating cell, and passing light from one fibre through the cell to the other fibre, the amount of light passing through the cell could be measured. It was found that the amount of power entering the output fibre was greatest when a Müller cell was aligned in the same orientation as the fibres; but when the cell was rotated or removed from the trap altogether, the power output decreased dramatically. A dye called MitoTracker Orange, which fluoresces when struck by light, was then injected into the Müller cells, enabling the researchers to visualize the path of light. This confirmed that light was indeed passing straight through the cells.

This elegant set of experiments shows that the Müller cells function as conduits which guide the passage of light through the tissue of the retina. The funnel-like structures observed are the endfeet of the Müller cells, which are densely packed and form a cobblestone pattern on the membrane closest to the vitreous humour of the eye. During the laser trap experiments, one of the fibres was misaligned so that, in the absence of a Müller cell, the light did not strike the second fibre; when a Müller cell was then placed between the two fibres, it captured the light from the first fibre and guided it towards the second. Thus, the endfeet seem to be crucial in capturing divergent rays of light and guiding them towards the photoreceptors at the back of the retina. They also have a lower refractive index than other parts of the Müller cell and other cells in the retina, and serve to minimize reflection of incident light as it passes from the vitreous humour into the uppermost layers of the retina.

The way in which Müller cells transport light is similar to the mechanism by which the optical fibres in fibre optic plates carry light. Fibre optic plates consist of optic fibres bundled together, and are used instead of lenses to transfer images between distant locations; this occurs without distortion of the image or loss of image detail. Müller cells may perform the same function in the retina; each one is coupled to one cone photoreceptor and (in guinea pigs and humans) ten rods; the Müller cell arrays could therefore faithfully transmit the pattern of light falling on the front of the retina to the photoreceptors at the back of the retina, thus minimizing distortion of the image. And, because the Müller cells are funnel-shaped and narrow, they take up only 20% of the space in the retina; this leaves plenty of room within the tissue for the neural circuitry.


Franze, K., et al. (2007). Müller cells are living optic fibers in the vertebrate retina. PNAS doi: 10.1073/pnas.0611180104. [Abstract]