Frank S. Werblin

Requirement for Cholinergic Synaptic Transmission in the Propagation of Spontaneous Retinal Waves

Highly correlated neural activity in the form of spontaneous waves of action potentials is present in the developing retina weeks before vision. Optical imaging revealed that these waves consist of spatially restricted domains of activity that form a mosaic pattern over the entire retinal ganglion cell layer. Whole-cell recordings indicate that wave generation requires synaptic activation of neuronal nicotinic acetylcholine receptors on ganglion cells. The only cholinergic cells in these immature retinas are a uniformly distributed, bistratified population of amacrine cells, as assessed by antibodies to choline acetyltransferase. The results indicate that the major source of synaptic input to retinal ganglion cells is a system of cholinergic amacrine cells, whose activity is required for wave propagation in the developing retina.

Mechanisms and circuitry underlying directional selectivity in the retina

In the retina, directionally selective ganglion cells respond with robust spiking to movement in their preferred direction, but show minimal response to movement in the opposite, or null, direction. The mechanisms and circuitry underlying this computation have remained controversial. Here we show, by isolating the excitatory and inhibitory inputs to directionally selective cells and measuring direct connections between these cells and presynaptic neurons, that a presynaptic interneuron, the starburst amacrine cell, delivers direct inhibition to directionally selective cells. The processes of starburst cells are connected asymmetrically to directionally selective cells: those pointing in the null direction deliver inhibition; those pointing in the preferred direction do not. Starburst cells project inhibition laterally ahead of a stimulus moving in the null direction. In addition, starburst inhibition is itself directionally selective: it is stronger for movement in the null direction. Excitation in response to null direction movement is reduced by an inhibitory signal acting at a site that is presynaptic to the directionally selective cell. The interplay of these components generates reduced excitation and enhanced inhibition in the null direction, thereby ensuring robust directional selectivity.

The analogic cellular neural network as a bionic eye

The conception of the CNN universal machine has led quite naturally to the invention of the analogic CNN bionic eye (henceforth referred to simply as the bionic eye). the basic idea is to combine the elementary functions, the building blocks, of the retina and other 2 1/2 D sensory organs, algorithmically, in a stored programme of a CNN universal machine, through the use of artificial analogic programmes. the term bionic is defined in a rigorous way: it is a nonlinear, dynamic, spatiotemporal biological model implemented in a stored programme electronic (optoelectronic) device; this device is in our case the analogic CNN universal machine (or chip). The aim of this paper is to report on this new invention, particularly to electronic and computer engineers, in a tutorial way. We begin by summarizing (1) the biological aspects of the range of retinal function (the retinal universe), (2) the CNN paradigm and the CNN universal machine architecture and (3) the general principles of retinal modelling in CNN. Next we describe new CNN circuit and template design innovations that can be used to implement physiological functions in the retina and other sensory organs using the CNN universal machine. Finally we show how to combine given retinal functional elements implemented in the CNN universal machine with analogic algorithms to form the bionic retina. the resulting system can be used not only for simulating biological retinal function but also for generating functions that go far beyond biological capabilities. Several bionic retina functions, different topographic modalities and analogic CNN algorithms can then be combined to form the analogic CNN bionic eye. the qualitative aspects of the models, especially the range of dynamics and accuracy considerations in VLSI optoelectronic implementations, are outlined. Finally, application areas of the bionic eye and possibilities of constructing innovative devices based on this invention (such as the bionic eyeglass or the visual mouse) are described.

Directional Selectivity Is Formed at Multiple Levels by Laterally Offset Inhibition in the Rabbit Retina

The excitatory and inhibitory inputs to directionally selective (DS) ganglion cells are themselves directionally selective. Directionality is achieved because excitation is reduced during null-direction movement along a GABAergic pathway. Inhibition is reduced during preferred-direction movement along a pathway that includes cholinergic synapses. Both excitation and inhibition are made directional by laterally offset inhibitory signals similar to the spatial offset of the direct inhibitory input to the DS cell dendrites. Thus, spatially offset lateral inhibition generates directionality at three different levels in the DS circuitry. We also found that for stimuli falling within the dendritic field, cholinergic input is delivered to the OFF but not the ON dendrites. Cholinergic pathways from outside the dendritic field reach both ON and OFF dendrites, but both of these pathways are normally inactivated by GABAergic synapses.

Lateral Interactions at Inner Plexiform Layer of Vertebrate Retina: Antagonistic Responses to Change

Lateral interactions at the inner plexiform layer of the retina of the mudpuppy were studied intracellularly after they were isolated from interactions at the outer plexiform layer with a special stimulus. The isolation was confirmed by recording no surround effect at bipolar cells under conditions that elicited a strong surround effect at ganglion cells. It appears that amacrine cell, which respond to spatiotemporal change at one retinal region, inhibit the response to change in on-off ganglion cells at adjacent sites.

A CNN framework for modeling parallel processing in a mammalian retina

We present here a simple multi-layer cellular neural/non-linear network (CNN) model of the mammalian retina, capable of implementation on CNN Universal Machine (CNN-UM) chips. The basis of the model is a simple multi-layer cellular neural/non-linear Network (IEEE Trans. Circuits Systems 1988; 35:1257; IEEE Trans. Circuits Systems 1993; 40:147). The characterization of the elements in the CNN model is based on anatomical and physiological studies performed in the rabbit retina. The living mammalian retina represents the visual world in a set of about a dozen different ‘feature detecting’ parallel representations (Nature 2001; 410:583–587). Our CNN model is capable of reproducing qualitatively the same full set of space–time patterns as the living retina in response to a flashed square. The modelling framework can then be used to predict the set of retinal responses to more complex patterns and is also applicable to studies of the other biological sensory systems. The work represents a major step forward in the complexity and programmability of retinal models. Copyright

Noise analysis of the glutamate-activated current in photoreceptors

The glutamate-activated current in photoreceptors has been attributed both to a sodium/glutamate transporter and to a glutamate-activated chloride channel. We have further studied the glutamate-activated current in single, isolated photoreceptors from the tiger salamander using noise analysis on whole-cell patch-clamp recordings. In cones, the current is generated by chloride channels with a single-channel conductance of 0.7 pS and an open lifetime of 2.4 ms. The number of channels per cell is in the range of 10,000-20,000. Activation of the channels requires the presence of both glutamate and sodium. The single-channel conductance and the open lifetime of the channel are independent of the external concentration of glutamate and sodium. External glutamate and sodium affect only the opening rate of the channels. D,L-Threo-3-hydroxyaspartate (THA), a glutamate-transport blocker, is shown to be a partial agonist for the channel. The single-channel conductance is the same regardless of whether glutamate or THA is the ligand, but the open lifetime of the channel is only 0.8 ms with THA as ligand. The glutamate-activated current in rods has a similar single-channel conductance (0.74 pS) and open lifetime (3 ms). We propose a kinetic model, consistent with these results, to explain how a transporter can simultaneously act both as a sodium/glutamate-gated chloride channel and a glutamate/sodium cotransporter.

The computational eye

Specialized cells in the eye work in parallel for unequaled image processing and computation. Millionfold swings in light intensity from the outside world, transformed to electrical signals, are processed in space and time for contrast and edge enhancement, as well as to detect motion.

Differential Targeting of Optical Neuromodulators to Ganglion Cell Soma and Dendrites Allows Dynamic Control of Center-Surround Antagonism

Retinal degenerative diseases cause photoreceptor loss and often result in remodeling and deafferentation of the inner retina. Fortunately, ganglion cell morphology appears to remain intact long after photoreceptors and distal retinal circuitry have degenerated. We have introduced the optical neuromodulators channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR) differentially into the soma and dendrites of ganglion cells to recreate antagonistic center-surround receptive field interactions. We then reestablished the physiological receptive field dimensions of primate parafoveal ganglion cells by convolving Gaussian-blurred versions of the visual scene at the appropriate wavelength for each neuromodulator with the Gaussians inherent in the soma and dendrites. These Gaussian-modified ganglion cells responded with physiologically relevant antagonistic receptive field components and encoded edges with parafoveal resolution. This approach bypasses the degenerated areas of the distal retina and could provide a first step in restoring sight to individuals suffering from retinal disease.

Crossover inhibition in the retina: circuitry that compensates for nonlinear rectifying synaptic transmission

In the mammalian retina, complementary ON and OFF visual streams are formed at the bipolar cell dendrites, then carried to amacrine and ganglion cells via nonlinear excitatory synapses from bipolar cells. Bipolar, amacrine and ganglion cells also receive a nonlinear inhibitory input from amacrine cells. The most common form of such inhibition crosses over from the opposite visual stream: Amacrine cells carry ON inhibition to the OFF cells and carry OFF inhibition to the ON cells (”crossover inhibition”). Although these synapses are predominantly nonlinear, linear signal processing is required for computing many properties of the visual world such as average intensity across a receptive field. Linear signaling is also necessary for maintaining the distinction between brightness and contrast. It has long been known that a subset of retinal outputs provide exactly this sort of linear representation of the world; we show here that rectifying (nonlinear) synaptic currents, when combined thorough crossover inhibition can generate this linear signaling. Using simple mathematical models we show that for a large set of cases, repeated rounds of synaptic rectification without crossover inhibition can destroy information carried by those synapses. A similar circuit motif is employed in the electronics industry to compensate for transistor nonlinearities in analog circuits.