B ACKGROUND

1.1.1 Morphology and physiology of retina

The retina is a thin sheet of brain tissue (100 to 250µm thick) that grows out into the eye to provide neural processing for photoreceptor signals. It includes both photoreceptor and the first twp to four stages of neural processing. Its output projects centrally over many axons, and analysis of these information channels occupies about half of the cerebral cortex. Moreover, it comprises about 75 discrete neuron types connected in specific, highly stereotyped patterns. It sends different

‘images’ of the outside world to the brain – an image of contours (line drawing), a color image (watercolor painting) or an image of moving objects (movie). This is commonly referred to as parallel processing and starts as early as the first synapse of the retina, the cone pedicle. The schematic of the mammalian retina is shown in Fig. 1.1 [1]. There are six classes of neuron in the mammalian retina: rod (1), cones (2), horizontal cells (3), bipolar cells (4), amacrine cells (5), and retinal ganglion cells (RGCs) (6). They have a laminar distribution (OS/IS, outer and inner segments of rods and cones; ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer;

IPL, inner plexiform; GCL, ganglion cell layer; NFL, optic nerve fiber layer). Rods and cones together are labeled as photoreceptors.

As the synaptic terminals of rods and cones, the light-evoked signals are transferred onto bipolar and horizontal cells. Horizontal cells, of which there are between one and three types in mammalian retinas, provide lateral interactions in the outer plexiform layer. One type of rod bipolar cell and at least nine types of cone bipolar cell transfer the light signals into the inner plexiform layer (IPL), onto the dendrites of amacrine and ganglion cells. Cone bipolar cells fall into two main groups: ON and OFF bipolar cells. Amacrine cells are inhibitory interneurons, and there are as many as 50 morphological types. Ganglion cell dendrites collect the signals to the visual center of the brain. At least 10-15 morphological types of ganglion cell are found in any mammalian retina. The

major cell types of a typical mammalian retina are shown in Fig. 1.2 [2]. The cells are introduced below:

Photoreceptor:

The photoreceptor mosaic is optimized to cover the full range of environmental light intensity (1010). This design specification requires two types of detected with different sensitivities, the rod and the cone. The rod serves under starlight where photons are so sparse that over 0.2 second (the rod integration time), they cause only~1 photoisomerization (R*)/10,000 rods. Consequently, under starlight and for 3 log units brighter, a rod must give a binary response reporting over each integration time the occurrence of either 0 or 1R*. The rod continues to serve at dawn as photons arrive more densely, providing more than one R*/integration time. The rod sums these linearly up to 20R*/integration time and then gradually saturates, with 100 R* evoking a maximal photocurrent of

~20pA.

The cone serves under full daylight, beginning when photon density reaches ~100 photons/receptor/integration time. The cone actually absorbs and transduces single photons, but because its gain is 50-fold lower than the rod’s, it requires 100 R* for the signal to rise above the continuous dark noise. By 1000R*/integration time, when rods are nearly saturated, the cone responds strongly. The cone photocurrent saturates at 30~pA (similar to the rod), but this occurs at much higher intensities up to 10⁶R*/cone/integration time. Consequently, whereas the rod signal is at first binary and then graded, but always corrupted by photon noise, the cone signal is always graded and far less noisy. Thus, the so-called photoreceptors in silicon retinas are actually cones.

Horizontal cell:

Horizontal cell dendrites are inserted as lateral elements into the invaginating contacts of cone pedicles, and horizontal cell axon terminals form the lateral elements within rod spherules. It is assumed that horizontal cells release the inhibitory transmitter and provide feedback inhibition at the photoreceptor synaptic terminal. As horizontal cells summate light signals from several cones, such feedback would cause lateral inhibition, through which a cone’s light response is reduced by the

illumination of neighboring cones. This mechanism is though to enhance the response to the edges of visual stimuli and to reduce the response to areas of uniform brightness. There is also evidence that light-dependent release of GABA from horizontal cells provides feed-forward inhibition of bipolar cell dendrites. Irrespective of their precise mode of action, horizontal cells sum light responses across a broad region, and subtract it from the local signal. Because horizontal cells are coupled through gap junctions, their receptive fields can be much wider than their dendritic fields.

Bipolar cells:

Bipolar cell types of the primate retina are shown in Fig. 1.3 [3]. Their axons terminate at different levels in the IPL; those terminating in the outer half are putative OFF cone bipolar cells, and those terminating in the inner half are ON bipolar cells. The axons of OFF and ON cone bipolar cells terminate at different levels (strata) within the IPL: OFF in the outer half, ON in the inner half.

However, superimposed on this ON/OFF dichotomy, further bipolar cell types have been described in Fig. 1.3 and every mammalian retina that has been studied contains at least four types of OFF and four types of ON cone bipolar cell [4], [5]. We are just beginning to understand their functional roles [6]. Axons that carry more transient OFF light signals terminate in the middle of the IPL; those that carry sustained OFF light signals are found in a more peripheral position [7], [8].

Amacrine cells:

There are twenty-nine types of amacrine cells. All retinal ganglion cells receive input from cone bipolar cells, but most direct synapses on the ganglion cells are from amacrine cells. The exact fraction varies among different functional types of ganglion cells, ranging from roughly 70% for alpha cells (large, movement-sensitive ganglion cells found in most mammals) to 50% for the midget ganglion cells located in the monkey central fovea. Amacrine cells also make inhibitory synapses on the axon terminals of bipolar cells, thus controlling their output to ganglion cells. In contrast to horizontal cells, which have a single broad role, amacrine cells have dedicated functions – they carry out narrow tasks concerned with shaping and control of ganglion cell responses. The different amacrine cells have distinct pre- and postsynaptic partners, contain a

variety of neurotransmitters. Amacrine cells seem to account for correlated firing among ganglion cells. Shared input from a common amacrine cell will tend to make ganglion cells fire together [2].

Ganglion cells:

The retinal ganglion cells summarized signals of previous retinal cells, and then send neural spiking to the brain. They have been found to diverse in both stratification and physiological properties. There are at least 10-15 different morphological types of ganglion cell in any mammalian retina [3], [9]. The underlying belief is that cells with distinct morphologies have distinct physiological functions. It was thought that they represented feature detectors that react to specific light stimuli. Among them were direction selective ganglion cells, which respond to light spots that move in a certain direction across their receptive field. In the primate retina, two types of concentrically organized receptive field have been found. One type showed no chromatic receptive field organization, whereas in the other type the centre and surround were chromatically selective [10]. The detailed classification of ganglion cells is described in section 1.1.2.

1.1.2 The classification of ganglion cells of the rabbits’ retina

The physiological classification of ganglion cells has been the most detailed in rabbit of any mammalian species. So the classification of ganglion cells of the rabbit in introduced here. Many neuroscientists have made classifications of ganglion cells. Although there are areas of disagreement all neuroscientists confirm this diversity. Morphologically, the retinal ganglion cells are divided into two types of concentrically organized receptive fields, one with a small, linearly summing receptive field center (X cell) and another with a large, non-linear responsive area (Y cell). In the cat, the correspondence between X-cells and β, and Y-cells and α was established long ago, as was the analogous match between P and M, midget and parasol cells in the monkey [2]. Physiologically, the retinal ganglion cells are divided into ON center/OFF surround and OFF center/ON surround cells [1].

In the thesis, the classification of [11], [12] is adopted. Here the ganglion cells are divided into

with concentric receptive fields and with complex receptive fields. Concentric ganglion cells were those that had ON or OFF centers with antagonistic surrounds and were classified into different group by extracellular recordings of their ON- or OFF-center response sign, excitatory receptive field center size, linearity of spatial summation, and brisk vs. sluggish and transient vs.sustained response to step changes in light intensity [11]. Ganglion cells that had complex receptive field properties are ON-OFF and ON direction-selective cells, orientation-selective cells, local edge detectors and uniformity detectors. Cells were first classified by their characteristic extracellular response to manually controlled stimuli similar to those which have been used in previous in vivo studies [12]. The recorded cell types are presented in Table 1.1 [13]. In [13], space-time patterns of concentric ganglion cells are reported. Spiking patterns of five different classes of ganglion cells are shown in Fig. 1.4. We can see in Fig. 2.4 that even for the same cell, the space-time patterns vary in every record.

Based on the results of [13], a simple multi-layer cellular neural /non-linear network (CNN) model was built [14]. Fig. 2.5 is a sketch of the processing structure of the CNN model of the mammalian rabbit retina. Each layer of a neuron-type is represented by a horizontal line. The vertical lines represent the connections between cell types. The third row contains the retina output cells, where the names are the neurobiologic names and their positive input is the bipolar layer, and their negative inputs are amacrine FF layers. In chapter 2, the ON Sluggish sustain ganglion cell is chosen to verify the design methodology proposed in this thesis.

1.2 O

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