Off-center Response Research Articles

Learning to see again: Perceptual learning of simulated abnormal on- off-cell population responses in sighted individuals

Many forms of artificial sight recovery, such as electronic implants and optogenetic proteins, generally cause simultaneous, rather than complementary firing of on- and off-center retinal cells. Here, using virtual patients—sighted individuals viewing distorted input—we examine whether plasticity might compensate for abnormal neuronal population responses. Five participants were dichoptically presented with a combination of original and contrast-reversed images. Each image (I) and its contrast-reverse (Iʹ) was filtered using a radial checkerboard (F) in Fourier space and its inverse (Fʹ). [I * F′] + [Iʹ * F] was presented to one eye, and [I * F] + [Iʹ * F′] was presented to the other, such that regions of the image that produced on-center responses in one eye produced off-center responses in the other eye, and vice versa. Participants continuously improved in a naturalistic object discrimination task over 20 one-hour sessions. Pre-training and post-training tests suggest that performance improvements were due to two learning processes: learning to recognize objects with reduced visual information and learning to suppress contrast-reversed image information in a non–eye-selective manner. These results suggest that, with training, it may be possible to adapt to the unnatural on- and off-cell population responses produced by electronic and optogenetic sight recovery technologies.

Visual Stimulation Reverses the Directional Preference of Direction-Selective Retinal Ganglion Cells

Direction selectivity in the retina is mediated by direction-selective ganglion cells. These cells are part of a circuit in which they are asymmetrically wired to inhibitory neurons. Thus, they respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite (null) direction. Here, we demonstrate that adaptation with short visual stimulation of a direction-selective ganglion cell using drifting gratings can reverse this cell's directional preference by 180°. This reversal is robust, long lasting, and independent of the animal's age. Our findings indicate that, even within circuits that are hardwired, the computation of direction can be altered by dynamic circuit mechanisms that are guided by visual stimulation.

Rapid Plasticity of Visual Responses in the Adult Lateral Geniculate Nucleus

Compared to the developing visual system, where neuronal plasticity has been well characterized at multiple levels, little is known about plasticity in the adult, particularly within subcortical structures. We made intraocular injections of 2-amino-4-phosphonobutyric acid (APB) in adult cats to block visual responses in On-center retinal ganglion cells and examined the consequences on visual responses in the lateral geniculate nucleus (LGN) of the thalamus. In contrast to current views of retinogeniculate organization, which hold that On-center LGN neurons should become silent with APB, we find that ∼50% of On-center neurons rapidly develop Off-center responses. The time course of these emergent responses and the actions of APB in the retina indicate the plasticity occurs within the LGN. These results suggest there is greater divergence of retinogeniculate connections than previously recognized and that functionally silent, nonspecific retinal inputs can serve as a substrate for rapid plasticity in the adult.

Functional polarity of dendrites and axons of primate A1 amacrine cells

The A1 cell is an axon-bearing amacrine cell of the primate retina with a diffusely stratified, moderately branched dendritic tree (approximately 400 microm diameter). Axons arise from proximal dendrites forming a second concentric, larger arborization (>4 mm diameter) of thin processes with bouton-like swellings along their length. A1 cells are ON-OFF transient cells that fire a brief high frequency burst of action potentials in response to light (Stafford & Dacey, 1997). It has been hypothesized that A1 cells receive local input to their dendrites, with action potentials propagating output via the axons across the retina, serving a global inhibitory function. To explore this hypothesis we recorded intracellularly from A1 cells in an in vitro macaque monkey retina preparation. A1 cells have an antagonistic center-surround receptive field structure for the ON and OFF components of the light response. Blocking the ON pathway with L-AP4 eliminated ON center responses but not OFF center responses or ON or OFF surround responses. Blocking GABAergic inhibition with picrotoxin increased response amplitudes without affecting receptive field structure. TTX abolished action potentials, with little effect on the sub-threshold light response or basic receptive field structure. We also used multi-photon laser scanning microscopy to record light-induced calcium transients in morphologically identified dendrites and axons of A1 cells. TTX completely abolished such calcium transients in the axons but not in the dendrites. Together these results support the current model of A1 function, whereby the dendritic tree receives synaptic input that determines the center-surround receptive field; and action potentials arise in the axons, which propagate away from the dendritic field across the retina.

In Vivo Imaging Reveals Dendritic Targeting of Laminated Afferents by Zebrafish Retinal Ganglion Cells

Targeting of axons and dendrites to particular synaptic laminae is an important mechanism by which precise patterns of neuronal connectivity are established. Although axons target specific laminae during development, dendritic lamination has been thought to occur largely by pruning of inappropriately placed arbors. We discovered by in vivo time-lapse imaging that retinal ganglion cell (RGC) dendrites in zebrafish show growth patterns implicating dendritic targeting as a mechanism for contacting appropriate synaptic partners. Populations of RGCs labeled in transgenic animals establish distinct dendritic strata sequentially, predominantly from the inner to outer retina. Imaging individual cells over successive days confirmed that multistratified RGCs generate strata sequentially, each arbor elaborating within a specific lamina. Simultaneous imaging of RGCs and subpopulations of presynaptic amacrine interneurons revealed that RGC dendrites appear to target amacrine plexuses that had already laminated. Dendritic targeting of prepatterned afferents may thus be a novel mechanism for establishing proper synaptic connectivity.

Spontaneous Retinal Activity Mediates Development of Ocular Dominance Columns and Binocular Receptive Fields in V1

The mechanisms that give rise to ocular dominance columns (ODCs) during development are controversial. Early experiments indicated a key role for retinal activity in ODC formation. However, later studies showed that in those early experiments, the retinal activity perturbation was initiated after ODCs had already formed. Moreover, recent studies concluded that early eye removals do not impact ODC segregation. Here we blocked spontaneous retinal activity during the very early stages of ODC development. This permanently disrupted the anatomical organization of ODCs and led to a dramatic increase in receptive field size for binocular cells in primary visual cortex. Our data suggest that early spontaneous retinal activity conveys crucial information about whether thalamocortical axons represent one or the other eye and that this activity mediates binocular competition important for shaping receptive fields in primary visual cortex.

Visual Experience before Eye-Opening and the Development of the Retinogeniculate Pathway

Visual experience before eye-opening is not usually thought to have any developmental significance. Here we show that naturalistic visual stimuli presented through unopened eyelids robustly activate neurons in the ferret dorsal lateral geniculate nucleus. Further, dark-rearing prior to natural eye-opening has striking effects upon geniculate physiology. Receptive field maps after dark-rearing show increased convergence of On- and Off-center responses, and neurons frequently respond to both bright and dark phases of drifting gratings. There is also increased selectivity for the orientation of the gratings. These abnormalities of On-Off segregation can be explained by the finding that the responses of immature On and Off cells to naturalistic stimuli are strongly anticorrelated.

Optimal template matching by nonorthogonal image expansion using restoration

In this paper we present a novel approach for template matching. The basic principle is expansion matching and it entails signal expansion into a set of nonorthogonal templatesimilar basis functions. The coefficients of this expansion signify the presence of the template in the corresponding locations in the image. We demonstrate that this matching technique is robust in conditions of noise, superposition, and severe occlusion. A new and more practical discriminative signal-to-noise ratio (DSNR) for matching is proposed that considers even the filter's off-center response to the template as “noise”. We show that expansion yields the optimal linear operator that maximizes the DSNR and results in a sharp response to the matched template. Theoretical and experimental comparisons of expansion matching and the widely used correlation matching demonstrate the superiority of our approach. Correlation matching (also known as matched filtering) yields broad peaks and spurious responses, both of which hamper good detection. We also show that the special case of expansion with a dense set of self-similar basis functions is equivalent to signal restoration. Expansion matching can be implemented by restoration techniques and also by our recently developed lattice architecture.

Nonorthogonal Image Expansion Related to Optimal Template Matching in Complex Images

Expansion matching (EXM) is a novel method for template matching that optimizes a new similarity measure called discriminative signal-to-noise ratio (DSNR). Since EXM is designed to minimize off-center response, it yields results with very sharp matching peaks. EXM yields superior performance to the widely used correlation matching (also known as matched filtering), especially in conditions of noise, superposition, and severe occlusion. This paper presents an extended EXM formulation that matches multiple templates in the complex image domain. Complex template matching is useful in matching frequency domain templates and edge gradient images, and can be extended to multispectral images as well. Here, a single filter is designed to simultaneously match a set of given complex templates with optimal DSNR, while eliciting user-defined center responses for each template. It is shown that when the complex case is simplified to the case of matching a single real template, the result reduces exactly to the minimum squared error (MSE) restoration filter assuming the template as the blurring function. Here, we introduce a new generalized MSE restoration paradigm based on the analogy to multiple-template EXM. Furthermore, the output of the single-template EXM filter is also shown to be equivalent to a nonorthogonal expansion of the image with basis functions that are all shifted versions of the template. Experimental results prove that EXM is robust to minor rotation and scale distortions.

Nonorthogonal Image Expansion Related to Optimal Template Matching in Complex Images

Expansion matching (EXM) is a novel method for template matching that optimizes a new similarity measure called discriminative signal-to-noise ratio (DSNR). Since EXM is designed to minimize off-center response, it yields results with very sharp matching peaks. EXM yields superior performance to the widely used correlation matching (also known as matched filtering), especially in conditions of noise, superposition, and severe occlusion. This paper presents an extended EXM formulation that matches multiple templates in the complex image domain. Complex template matching is useful in matching frequency domain templates and edge gradient images, and can be extended to multispectral images as well. Here, a single filter is designed to simultaneously match a set of given complex templates with optimal DSNR, while eliciting user-defined center responses for each template. It is shown that when the complex case is simplified to the case of matching a single real template, the result reduces exactly to the minimum squared error (MSE) restoration filter assuming the template as the blurring function. Here, we introduce a new generalized MSE restoration paradigm based on the analogy to multiple-template EXM. Furthermore, the output of the single-template EXM filter is also shown to be equivalent to a nonorthogonal expansion of the image with basis functions that are all shifted versions of the template. Experimental results prove that EXM is robust to minor rotation and scale distortions.

Optimal edge detection using expansion matching and restoration

Discusses the application of a newly developed expansion matching method for edge detection. Expansion matching optimizes a novel matching criterion called the discriminative signal-to-noise ratio (DSNR) and has been shown to robustly recognize templates under conditions of noise, severe occlusion and superposition. The DSNR criterion is better suited to evaluate matching in practical conditions than the traditional SNR since it considers as even the off-center response of the filter to the template itself. We introduce a family of optimal DSNR edge detectors based on the expansion filter for several edge models. For step edges, the optimal DSNR step expansion filter (SEF) is compared with the widely used Canny edge detector (CED). Experimental comparisons show that our edge detector yields better performance than the CED in terms of DSNR even under very adverse noise conditions. As for boundary detection, the SEF consistently yields higher figures of merit than the CED on a synthetic binary image over a wide range of noise levels. Results also show that the design parameters of size or width of the SEF are less critical than the CED variance. This means that a single scale of the SEF spans a larger range of input noise than a single scale of the CED. Experiments on a noisy image reveal that the SEF yields less noisy edge elements and preserves structural details more accurately. On the other hand, the CED output has better suppression of multiple responses than the corresponding SEF output. >

The segregation of ON- and OFF-center responses in the lateral geniculate nucleus of normal and monocularly enucleated ferrets.

We have investigated the distribution of ON- and OFF-center responses in the lateral geniculate nucleus of ferrets with normal and abnormal retinal projections. Electrophysiological recordings in normal pigmented animals confirm previous studies on mustelids showing that ON-center responses are found in the anterior, inner parts of laminae A and A1 and OFF-center responses in posterior, outer leaflets. In albino animals, lamina A displays normal patterns of ON/OFF segregation but in lamina A1', which receives an abnormal crossed retinal projection, no consistent patterns of segregation are found. Following monocular enucleation on the day of birth, the uncrossed projection in pigmented ferrets remains expanded across the LGN. Anatomically and physiologically, this projection is segregated into two leaflets: an anterior, inner ON-center leaflet and a posterior outer OFF-center leaflet. We conclude that the persistence of ON/OFF segregation, independent of geniculate location, suggests that self-sorting of retinal input is an important factor in generating the segregation.

Innervation patterns of single physiologically identified geniculocortical axons in the striate cortex of the tree shrew.

We examined the termination patterns of single geniculocortical axons in the striate cortex of the tree shrew by using intracellular recording and horseradish peroxidase staining methods. Axons were classified by whether they responded to light onset (ON center) or light offset (OFF center) and whether they were driven by the ipsi- or contralateral eye. Afferents with ON-center responses end in the upper part of layer IV (IVa) whereas afferents with OFF-center responses end in the lower part of layer IV (IVb). Within each tier, axons driven by the ipsilateral and contralateral eye overlap. These results suggest that binocular convergence occurs within layer IV without mixing the information from the ON- and OFF-center pathways and we consider the significance of this arrangement for visual cortical function.

Morphologies of rabbit retinal ganglion cells with concentric receptive fields.

Rabbit retinal ganglion cells with concentric receptive fields were intracellularly recorded and stained in the isolated superfused eyecup preparation to relate specific physiological response properties to dendritic morphology. Concentric ganglion cells, as traditionally defined, were those that had On or Off centers with antagonistic surrounds but lacked complex response properties such as direction or orientation selectivity. Concentric cells were classified into different groups 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 responses to step changes in light intensity. The cells were then impaled, confirmed in identity during intracellular recording, and iontophoretically injected with horseradish peroxidase for histological analysis. Twenty-three concentric ganglion cells were recovered and morphometrically analyzed. Their physiological response properties were found to be related to a number of underlying two- and three-dimensional attributes of the cell's dendritic branching patterns. The dendrites of all 20 brisk concentric cells and two of the three sluggish cells were found to ramify narrowly in either the proximal or distal half of the inner plexiform layer, corresponding to whether they are On center or Off center, respectively. One of the sluggish concentric cells was found to have a more complex, partially bistratified ramification. Physiologically identified brisk-sustained-linear, brisk-transient-nonlinear, brisk-transient-linear, and at least two classes of sluggish concentric ganglion cells were stained. Each of these physiological classes appears to exhibit a distinct and identifiable dendritic branching pattern.

Structural Basis for On- and Off-Center Responses in Retinal Bipolar Cells

Electron microscopy of Golgi preparations of goldfish retina shows that dendrites of type a (hyperpolarizing, off-center) bipolar cells make wide cleft junctions unassociated with synaptic ribbons, while those of type b (depolarizing, on-center) bioplar cells make narrow cleft junctions and synaptic ribbon contacts, with rods and cones. This suggests that wide cleft junctions are the site of sign-conserving, and narrow cleft junctions or ribbon contacts (or both) are the site of sign-inverting synaptic transmission from photoreceptors to bipolars.

Structural basis for ON-and OFF-center responses in retinal ganglion cells.

The inner plexiform layer of the mammalian retina has a bisublaminar organization determined by restricted branching of the terminals of cone bipolar cells and dendrites of class I (large) and class II (small) ganglion cells. Comparison of dendritic field diameters and receptive fiedl center sizes of large ganglion cells suggests that neural circuitry in sublamina a conveys "OFF"-center properties and connections in sublamina b "ON"-center properties to retinal ganglion cells.

Researches Into Vision

A series of neurophysiologic investigations which have been proceeding in recent years could have important ophthalmic applications. Yet, for reasons which we are fearful to probe, few of them have been reported in the ophthalmic literature. These are the investigations which had their inception in Hartline's demonstrations of excitatory-inhibitory fibers in the optic nerve of the horseshoe crab, their development in Kuffler's investigations of on-center and off-center responses in ganglion cells of the cat retina, and their present development in Hubel and Wiesel's analysis of occipital cell function in the cat's and monkey's visual system. All these experiments have been made possible by the availability of a technique for recording the electrical activity of individual neurons. This enabled Kuffler to find out that the spontaneous activity of an individual ganglion cell could be enhanced or inhibited by illuminating one spot on the retina and an opposite effect elicited by illuminating