scholarly journals Changes in physiological properties of rat ganglion cells during retinal degeneration

2011 ◽  
Vol 105 (5) ◽  
pp. 2560-2571 ◽  
Author(s):  
Chris Sekirnjak ◽  
Lauren H. Jepson ◽  
Pawel Hottowy ◽  
Alexander Sher ◽  
Wladyslaw Dabrowski ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Time Course ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Receptive Fields ◽  
Similar Rate ◽  
Visual Signals ◽  
Light Responses ◽  
Functional Changes ◽  
Physiological Properties

Retinitis pigmentosa (RP) is a leading cause of degenerative vision loss, yet its progressive effects on visual signals transmitted from the retina to the brain are not well understood. The transgenic P23H rat is a valuable model of human autosomal dominant RP, exhibiting extensive similarities to the human disease pathology, time course, and electrophysiology. In this study, we examined the physiological effects of degeneration in retinal ganglion cells (RGCs) of P23H rats aged between P37 and P752, and compared them with data from wild-type control animals. The strength and the size of visual receptive fields of RGCs decreased rapidly with age in P23H retinas. Light responses mediated by rod photoreceptors declined earlier (∼P300) than cone-mediated light responses (∼P600). Responses of ON and OFF RGCs diminished at a similar rate. However, OFF cells exhibited hyperactivity during degeneration, whereas ON cells showed a decrease in firing rate. The application of synaptic blockers abolished about half of the elevated firing in OFF RGCs, indicating that the remodeled circuitry was not the only source of degeneration-induced hyperactivity. These results advance our understanding of the functional changes associated with retinal degeneration.

Area MT Neurons Respond to Visual Motion Distant From Their Receptive Fields

2005 ◽  
Vol 94 (6) ◽  
pp. 4156-4167 ◽  
Author(s):  
Daniel Zaksas ◽  
Tatiana Pasternak
Keyword(s):  
Time Course ◽  
Visual Motion ◽  
Cognitive Task ◽  
Receptive Fields ◽  
Direction Selectivity ◽  
Task Demands ◽  
Visual Signals ◽  
Area Mt ◽  
Mt Neurons ◽  
Stimulus Offset

Neurons in cortical area MT have localized receptive fields (RF) representing the contralateral hemifield and play an important role in processing visual motion. We recorded the activity of these neurons during a behavioral task in which two monkeys were required to discriminate and remember visual motion presented in the ipsilateral hemifield. During the task, the monkeys viewed two stimuli, sample and test, separated by a brief delay and reported whether they contained motion in the same or in opposite directions. Fifty to 70% of MT neurons were activated by the motion stimuli presented in the ipsilateral hemifield at locations far removed from their classical receptive fields. These responses were in the form of excitation or suppression and were delayed relative to conventional MT responses. Both excitatory and suppressive responses were direction selective, but the nature and the time course of their directionality differed from the conventional excitatory responses recorded with stimuli in the RF. Direction selectivity of the excitatory remote response was transient and early, whereas the suppressive response developed later and persisted after stimulus offset. The presence or absence of these unusual responses on error trials, as well as their magnitude, was affected by the behavioral significance of stimuli used in the task. We hypothesize that these responses represent top-down signals from brain region(s) accessing information about stimuli in the entire visual field and about the behavioral state of the animal. The recruitment of neurons in the opposite hemisphere during processing of behaviorally relevant visual signals reveals a mechanism by which sensory processing can be affected by cognitive task demands.

scholarly journals Loss of Responses to Visual But Not Electrical Stimulation in Ganglion Cells of Rats With Severe Photoreceptor Degeneration

2009 ◽  
Vol 102 (6) ◽  
pp. 3260-3269 ◽  
Author(s):  
Chris Sekirnjak ◽  
Clare Hulse ◽  
Lauren H. Jepson ◽  
Pawel Hottowy ◽  
Alexander Sher ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Retinal Ganglion Cells ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Transgenic Rat ◽  
Direct Electrical Stimulation ◽  
Retinal Ganglion ◽  
Photoreceptor Degeneration ◽  
Wild Type ◽  
Light Responses

Retinal implants are intended to help patients with degenerative conditions by electrically stimulating surviving cells to produce artificial vision. However, little is known about how individual retinal ganglion cells respond to direct electrical stimulation in degenerating retina. Here we used a transgenic rat model to characterize ganglion cell responses to light and electrical stimulation during photoreceptor degeneration. Retinas from pigmented P23H-1 rats were compared with wild-type retinas between ages P37 and P752. During degeneration, retinal thickness declined by 50%, largely as a consequence of photoreceptor loss. Spontaneous electrical activity in retinal ganglion cells initially increased two- to threefold, but returned to nearly normal levels around P600. A profound decrease in the number of light-responsive ganglion cells was observed during degeneration, culminating in retinas without detectable light responses by P550. Ganglion cells from transgenic and wild-type animals were targeted for focal electrical stimulation using multielectrode arrays with electrode diameters of ∼10 microns. Ganglion cells were stimulated directly and the success rate of stimulation in both groups was 60–70% at all ages. Surprisingly, thresholds (∼0.05 mC/cm2) and latencies (∼0.25 ms) in P23H rat ganglion cells were comparable to those in wild-type ganglion cells at all ages and showed no change over time. Thus ganglion cells in P23H rats respond normally to direct electrical stimulation despite severe photoreceptor degeneration and complete loss of light responses. These findings suggest that high-resolution epiretinal prosthetic devices may be effective in treating vision loss resulting from photoreceptor degeneration.

Neurophysiology of central retinal degeneration in cat

1993 ◽  
Vol 10 (3) ◽  
pp. 499-509 ◽  
Author(s):  
W.R. Levick ◽  
L.N. Thibos
Keyword(s):  
Retinal Degeneration ◽  
Action Potentials ◽  
Ganglion Cells ◽  
Receptive Fields ◽  
Visual Sensitivity ◽  
Functional Classification ◽  
Normal Limits ◽  
Abnormal Form ◽  
Maintained Discharge ◽  
Orientation Bias

AbstractReceptive fields of ganglion cells have been studied in cats possessing a chronic, arrested lesion of central retinal degeneration. Lesions were characterized by an ophthalmoscopically sharp border separating apparently normal retina from the region of the lesion. Under direct ophthalmoscopic guidance, a succession of recordings was obtained from ganglion cells having cell bodies at various positions relative to the lesion. Cells located more than 1 deg outside the ophthalmoscopic border had normal visual sensitivity as assessed by area-threshold experiments. Inside the lesion cells within 1 deg of the border had reduced sensitivity which often precluded functional classification by the usual visual tests. Ganglion cells located more than 1 deg inside the border of large lesions were blind and some had abnormal patterns of maintained discharge of action potentials. Nevertheless, the antidromic latencies of these blind cells fell into the familiar conduction groups (T1/T2/T3). Receptive-field maps of cells near the border of the lesion often appeared truncated, with the missing portion of the field covered by the lesion. These observations were consistent with the abnormal form of area-thresholdcurves. Altlhough the responsiveness of cells near the lesion was abnormally low for grating stimuli, cutoff spatial frequency and orientation bias of these cells were within normal limits.

scholarly journals Intrinsic and Extrinsic Light Responses in Melanopsin-Expressing Ganglion Cells During Mouse Development

2008 ◽  
Vol 100 (1) ◽  
pp. 371-384 ◽  
Author(s):  
Tiffany M. Schmidt ◽  
Kenichiro Taniguchi ◽  
Paulo Kofuji
Keyword(s):  
Fluorescent Protein ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Artificial Chromosome ◽  
Inner Plexiform Layer ◽  
Mouse Development ◽  
Light Responses ◽  
Functional Changes ◽  
Electrophysiological Recordings ◽  
Green Fluorescent

Melanopsin (Opn4) is a photopigment found in a subset of retinal ganglion cells (RGCs) that project to various brain areas. These neurons are intrinsically photosensitive (ipRGCs) and are implicated in nonimage-forming responses to environmental light such as the pupillary light reflex and circadian entrainment. Recent evidence indicates that ipRGCs respond to light at birth, but questions remain as to whether and when they undergo significant functional changes. We used bacterial artificial chromosome transgenesis to engineer a mouse line in which enhanced green fluorescent protein (EGFP) is expressed under the control of the melanopsin promoter. Double immunolabeling for EGFP and melanopsin demonstrates their colocalization in ganglion cells of mutant mouse retinas. Electrophysiological recordings of ipRGCs in neonatal mice (postnatal day 0 [P0] to P7) demonstrated that these cells responded to light with small and sluggish depolarization. However, starting at P11 we observed ipRGCs that responded to light with a larger and faster onset (<1 s) and offset (<1 s) depolarization. These faster, larger depolarizations were observed in most ipRGCs by early adult ages. However, on application of a cocktail of synaptic blockers, we found that all cells responded to light with slow onset (>2.5 s) and offset (>10 s) depolarization, revealing the intrinsic, melanopsin-mediated light responses. The extrinsic, cone/rod influence on ipRGCs correlates with their extensive dendritic stratification in the inner plexiform layer. Collectively, these results demonstrate that ipRGCs make use of melanopsin for phototransduction before eye opening and that these cells further integrate signals derived from the outer retina as the retina matures.

A comparison of receptive-field and tracer-coupling size of amacrine and ganglion cells in the rabbit retina

1997 ◽  
Vol 14 (6) ◽  
pp. 1153-1165 ◽  
Author(s):  
Stewart A. Bloomfield ◽  
Daiyan Xin
Keyword(s):  
Receptive Field ◽  
Ganglion Cells ◽  
Electrical Coupling ◽  
Receptive Fields ◽  
Amacrine Cells ◽  
Visual Signals ◽  
Lateral Spread ◽  
Field Size ◽  
Electrical Networks ◽  
Mammalian Retina

AbstractRecent studies have shown that amacrine and ganglion cells in the mammalian retina are extensively coupled as revealed by the intercellular movement of the biotinylated tracers biocytin and Neurobiotin. These demonstrations of tracer coupling suggest that electrical networks formed by proximal neurons (i.e. amacrine and ganglion cells) may underlie the lateral propagation of signals across the inner retina. We studied this question by comparing the receptive-field size, dendritic-field size, and extent of tracer coupling of amacrine and ganglion cells in the dark-adapted, supervised, isolated retina eyecup of the rabbit. Our results indicate that while the center-receptive fields of proximal neurons are approximately 15% larger than their corresponding dendritic diameters, this slight difference can be explained by factors other than electrical coupling such as tissue shrinkage associated with histological processing. However, the extent of tracer coupling of amacrine and ganglion cells was, on average, about twice the size of the corresponding receptive fields. Thus, the receptive field of an individual proximal neuron matched far more closely to its dendritic diameter than to the size of the tracer-coupled network of cells to which it belonged. The exception to this rule was the AII amacrine cells for which center-receptive fields were 2–3 times the size of their dendritic diameters but matched closely to the size of the tracer-coupled arrays. Thus, with the exception of AII cells, our data indicate that tracer coupling between proximal neurons is not associated with an enlargement of their receptive fields. Our results, then, provide no evidence for electrical coupling or, at least, indicate that extensive lateral spread of visual signals does not occur in the proximal mammalian retina.

scholarly journals Inhibiting retinoic acid mitigates vision loss in a mouse model of retinal degeneration

2021 ◽  
Author(s):  
Michael Telias ◽  
Kevin Sit ◽  
Daniel Frozenfar ◽  
Benjamin Smith ◽  
Arjit Misra ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinal Degeneration ◽  
Cortical Neurons ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Causal Link ◽  
Vision Impairment ◽  
Orientation Tuning ◽  
Rods And Cones ◽  
Visual Cortical

In degenerative retinal disorders, rod and cone photoreceptors die, causing vision impairment and blindness. Downstream neurons survive but undergo morphological and physiological remodeling, with some retinal ganglion cells (RGC) exhibiting heightened spontaneous firing. Retinoic acid (RA) has been implicated as the key signaling molecule that induces RGC hyperactivity, obscuring RGC light responses and reducing light avoidance behaviors triggered by residual rods and cones. However, evidence that RA-dependent remodeling corrupts image-forming vision has been lacking. Here we show that disulfiram, an FDA-approved drug that inhibits RA synthesis, and BMS 493, an RA receptor (RAR) inhibitor, reduce RGC hyperactivity and augment image detection in visually impaired mice. Functional imaging of visual cortical neurons shows that disulfiram and BMS 493 sharpen orientation-tuning and strengthen response fidelity to naturalistic scenes. These findings establish a causal link between RA-induced retinal hyperactivity and vision impairment and define molecular targets and candidate drugs for boosting image-forming vision in retinal degeneration.

scholarly journals Melanopsin expression in the cornea

2018 ◽  
Vol 35 ◽  
Author(s):  
ANTON DELWIG ◽  
SHAWNTA Y. CHANEY ◽  
ANDREA S. BERTKE ◽  
JAN VERWEIJ ◽  
SUSANA QUIRCE ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Nerve Fibers ◽  
Visual Signals ◽  
Light Responses ◽  
Rods And Cones ◽  
Retinal Tissue ◽  
Antibody Staining ◽  
Electrophysiological Recordings ◽  
Pupil Constriction ◽  
Sensory Fibers

AbstractA unique class of intrinsically photosensitive retinal ganglion cells in mammalian retinae has been recently discovered and characterized. These neurons can generate visual signals in the absence of inputs from rods and cones, the conventional photoreceptors in the visual system. These light sensitive ganglion cells (mRGCs) express the non-rod, non-cone photopigment melanopsin and play well documented roles in modulating pupil responses to light, photoentrainment of circadian rhythms, mood, sleep and other adaptive light functions. While most research efforts in mammals have focused on mRGCs in retina, recent studies reveal that melanopsin is expressed in non-retinal tissues. For example, light-evoked melanopsin activation in extra retinal tissue regulates pupil constriction in the iris and vasodilation in the vasculature of the heart and tail. As another example of nonretinal melanopsin expression we report here the previously unrecognized localization of this photopigment in nerve fibers within the cornea. Surprisingly, we were unable to detect light responses in the melanopsin-expressing corneal fibers in spite of our histological evidence based on genetically driven markers and antibody staining. We tested further for melanopsin localization in cell bodies of the trigeminal ganglia (TG), the principal nuclei of the peripheral nervous system that project sensory fibers to the cornea, and found expression of melanopsin mRNA in a subset of TG neurons. However, neither electrophysiological recordings nor calcium imaging revealed any light responsiveness in the melanopsin positive TG neurons. Given that we found no light-evoked activation of melanopsin-expressing fibers in cornea or in cell bodies in the TG, we propose that melanopsin protein might serve other sensory functions in the cornea. One justification for this idea is that melanopsin expressed in Drosophila photoreceptors can serve as a temperature sensor.

Steady discharges of macaque retinal ganglion cells

1994 ◽  
Vol 11 (1) ◽  
pp. 111-118 ◽  
Author(s):  
J. B. Troy ◽  
B. B. Lee
Keyword(s):  
Serial Correlation ◽  
Ganglion Cells ◽  
Receptive Fields ◽  
Power Spectra ◽  
Correlation Coefficients ◽  
Visual Signals ◽  
Noise Power ◽  
Retinal Ganglion ◽  
Coefficients Of Variation ◽  
The Mean

AbstractSteady discharges were collected from ganglion cells of the magnocellular (MC) and parvocellular (PC) pathways of the macaque while their receptive fields were uniformly illuminated with a 4.7-deg steady yellow light of photopic illuminance. The mean rates, coefficients of variation, interval distributions, serial correlation coefficients, and power spectra of these discharges were determined. The results presented permit one to estimate the noise power in the discharges of macaque ganglion cells and hence determine how visual signals of different amplitudes will be affected by the noise resident in their discharges.Although there was some small serial correlation in the discharges of both MC- and PC-pathway cells, their discharges can be considered to result from renewal processes with reasonable accuracy. As with the discharges of cat ganglion cells, macaque ganglion cell discharges can be considered to have approximately gamma-distributed intervals. Steady discharges of MC- and PC-pathway cells show considerable overlap in their statistics, although small but significant differences are present.

Spatial and temporal integration in primary trigeminal nucleus of rattlesnake infrared system

1984 ◽  
Vol 51 (5) ◽  
pp. 1077-1090 ◽  
Author(s):  
L. R. Stanford ◽  
P. H. Hartline
Keyword(s):  
Time Course ◽  
Ganglion Cells ◽  
Temporal Integration ◽  
Receptive Fields ◽  
Trigeminal System ◽  
Afferent Neurons ◽  
Inhibitory Interaction ◽  
Primary Afferent Neurons ◽  
Primary Afferent ◽  
Motion Sensitivity

The spatial and temporal characteristics of the infrared responses of single neurons in the nucleus of the lateral descending trigeminal tract (LTTD) of the rattlesnake were investigated. The LTTD is the sole projection site of trigeminal neurons that innervate the thermoreceptive pit organ. In contrast to the responses of the primary infrared neurons, which have phasic and tonic components, the neurons in the LTTD respond strictly phasically to a sustained infrared stimulus. During an excitatory stimulus, the transient burst is followed by suppression of firing or by reduction of the new rate below the rate that would have occurred in the absence of stimulation. The phasic character of the responses may enable these neurons to encode more accurately changes in the pattern of infrared stimuli. Neurons in the LTTD show adaptation within limited regions of their receptive fields, while responses in other regions remain undiminished. This indicates that each LTTD neuron receives input from a population of primary infrared neurons. LTTD neurons respond to infrared stimuli of intensity less than 0.01 mW/cm2, which is below the threshold reported for primary afferent neurons; this also suggests convergence of a number of primary infrared afferents onto each LTTD neuron. LTTD neurons have smaller excitatory receptive fields than do the primary afferent neurons in the infrared system, indicating that spatial sharpening also occurs in this nucleus. Receptive fields of LTTD neurons may have inhibitory areas flanking the excitatory area. Introduction of a stimulus into the inhibitory area results in depression of the background discharge; thus, the inhibition is due to an active process, not to rebound from excitation. Inhibition can also be demonstrated by simultaneous stimulation of the excitatory and inhibitory receptive-field areas, resulting in a decreased excitatory response. We suggest that convergence of antagonistic excitatory and inhibitory inputs can explain the time course of LTTD responses to infrared stimulation and the architecture of LTTD receptive fields. Such excitatory and inhibitory interaction, similar to that postulated for the responses of some vertebrate retinal ganglion cells, could function to provide the basis for directional selectivity, motion sensitivity, and border enhancement in the infrared system. Unlike the visual system, however, in the infrared system excitatory-inhibitory interactions allow the construction of small excitatory receptive fields in the LTTD from the larger receptive fields of the primary afferent neurons, resulting in a highly evolved trigeminal system with visionlike function.

scholarly journals Pathway-specific asymmetries between ON and OFF visual signals

2018 ◽  
Author(s):  
Sneha Ravi ◽  
Daniel Ahn ◽  
Martin Greschner ◽  
E.J Chichilnisky ◽  
Greg D. Field
Keyword(s):  
Visual Processing ◽  
Functional Organization ◽  
Ganglion Cells ◽  
Temporal Integration ◽  
Receptive Fields ◽  
Visual Signals ◽  
Natural Scenes ◽  
Alpha Cells ◽  
Spatial Integration ◽  
On And Off Pathways

AbstractVisual processing is largely organized into ON and OFF pathways that signal stimulus increments and decrements, respectively. These pathways exhibit natural pairings based on morphological and physiological similarities, such as ON and OFF alpha ganglion cells in the mammalian retina. Several studies have noted asymmetries in the properties of ON and OFF pathways. For example, the spatial receptive fields (RFs) of OFF alpha cells are systematically smaller than ON alpha cells. Analysis of natural scenes suggests these asymmetries are optimal for visual encoding. To test the generality of ON-OFF asymmetries, we measured the spatiotemporal RF properties of multiple RGC types in rat retina. Through a quantitative and serial classification, we identified three functional pairs of ON and OFF RGCs. We analyzed the structure of their RFs and compared spatial integration, temporal integration, and gain across ON and OFF pairs. Similar to previous results from cat and primate, RGC types with larger spatial RFs exhibited briefer temporal integration and higher gain. However, each pair of ON and OFF RGC types exhibited distinct asymmetric relationships between receptive field properties, some of which were opposite to previous reports. These results reveal the functional organization of six RGC types in the rodent retina and indicate that ON-OFF asymmetries are pathway specific.Significance StatementCircuits that process sensory input frequently process increments separately from decrements, so called ‘ON’ and ‘OFF’ responses. Theoretical studies indicate this separation, and associated asymmetries in ON and OFF pathways, may be beneficial for encoding natural stimuli. However, the generality of ON and OFF pathway asymmetries has not been tested. Here we compare the functional properties of three distinct pairs of ON and OFF pathways in the rodent retina and show their asymmetries are pathway specific. These results provide a new view on the partitioning of vision across diverse ON and OFF signaling pathways

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