scholarly journals Nystagmus in patients with congenital stationary night blindness (CSNB) originates from synchronously firing direction-selective retinal ganglion cells

2019 ◽  
Author(s):  
Beerend H.J. Winkelman ◽  
Marcus H. Howlett ◽  
Maj-Britt Hölzel ◽  
Coen Joling ◽  
Kathryn H. Fransen ◽  
...  

AbstractCongenital nystagmus, involuntary oscillating small eye movements, is commonly thought to originate from aberrant interactions between brainstem nuclei and foveal cortical pathways. Here we investigated whether nystagmus associated with congenital stationary nightblindness (CSNB) can result from primary deficits in the retina. We found that CSNB patients as well as an animal model (nob mice), both of which lack functional nyctalopin protein (NYX, nyx) in ON bipolar cells (ON-BC) at their synapse with photoreceptors, showed oscillating eye movements at a frequency of 4-7Hz. nob ON direction selective ganglion cells (ON-DSGC), which detect global motion and project to the accessory optic system (AOS), oscillated with the same frequency as their eyes. In the dark, individual ganglion cells (GC) oscillated asynchronously, but their oscillations became synchronized by light stimulation. Likewise, both patient and nob mice oscillating eye movements were only present in the light. Retinal pharmacological manipulations that blocked nob ON-DSGC oscillations also eliminated their oscillating eye movements, and retinal pharmacological manipulations that reduced oscillation frequency of nob ON-DSGCs also reduced oscillation frequency of their eye movements. We conclude that, in nob mice, oscillations of retinal ON-DSGCs cause nystagmus with properties similar to those associated with CSNB in humans. These results show that the nob mouse is the first animal model for a form of congenital nystagmus paving the way for development of therapeutic strategies.

2011 ◽  
Vol 48 (15-16) ◽  
pp. 2151-2158 ◽  
Author(s):  
Purushottam Jha ◽  
Himanshu Banda ◽  
Ruslana Tytarenko ◽  
P.S. Bora ◽  
N.S. Bora

2017 ◽  
Vol 89 (2) ◽  
pp. 84-103 ◽  
Author(s):  
Heidrun Kuhrt ◽  
Andreas Bringmann ◽  
Wolfgang Härtig ◽  
Gudrun Wibbelt ◽  
Leo Peichl ◽  
...  

Elephants are precocial mammals that are relatively mature as newborns and mobile shortly after birth. To determine whether the retina of newborn elephants is capable of supporting the mobility of elephant calves, we compared the retinal structures of 2 newborn elephants (1 African and 1 Asian) and 2 adult animals of both species by immunohistochemical and morphometric methods. For the first time, we present here a comprehensive qualitative and quantitative characterization of the cellular composition of the newborn and the adult retinas of 2 elephant species. We found that the retina of elephants is relatively mature at birth. All retinal layers were well discernible, and various retinal cell types were detected in the newborns, including Müller glial cells (expressing glutamine synthetase and cellular retinal binding protein; CRALBP), cone photoreceptors (expressing S-opsin or M/L-opsin), protein kinase Cα-expressing bipolar cells, tyrosine hydroxylase-, choline acetyltransferase (ChAT)-, calbindin-, and calretinin-expressing amacrine cells, and calbindin-expressing horizontal cells. The retina of newborn elephants contains discrete horizontal cells which coexpress ChAT, calbindin, and calretinin. While the overall structure of the retina is very similar between newborn and adult elephants, various parameters change after birth. The postnatal thickening of the retinal ganglion cell axons and the increase in ganglion cell soma size are explained by the increase in body size after birth, and the decreases in the densities of neuronal and glial cells are explained by the postnatal expansion of the retinal surface area. The expression of glutamine synthetase and CRALBP in the Müller cells of newborn elephants suggests that the cells are already capable of supporting the activities of photoreceptors and neurons. As a peculiarity, the elephant retina contains both normally located and displaced giant ganglion cells, with single cells reaching a diameter of more than 50 µm in adults and therefore being almost in the range of giant retinal ganglion cells found in aquatic mammals. Some of these ganglion cells are displaced into the inner nuclear layer, a unique feature of terrestrial mammals. For the first time, we describe here the occurrence of many bistratified rod bipolar cells in the elephant retina. These bistratified bipolar cells may improve nocturnal contrast perception in elephants given their arrhythmic lifestyle.


1980 ◽  
Vol 190 (1) ◽  
pp. 49-61 ◽  
Author(s):  
Clyde W. Oyster ◽  
John I. Simpson ◽  
Ellen S. Takahashi ◽  
Robert E. Soodak

1997 ◽  
Vol 78 (2) ◽  
pp. 614-627 ◽  
Author(s):  
Naoki Kogo ◽  
Michael Ariel

Kogo, Naoki and Michael Ariel. Membrane properties and monosynaptic retinal excitation of neurons in the turtle accessory optic system. J. Neurophysiol. 78: 614–627, 1997. Using an eye-attached isolated brain stem preparation of a turtle, Pseudemys scripta elegans, in conjunction with whole cell patch techniques, we recorded intracellular activity of accessory optic system neurons in the basal optic nucleus (BON). This technique offered long-lasting stable recordings of individual synaptic events. In the reduced preparation (most of the dorsal structures were removed), large spontaneous excitatory synaptic inputs [excitatory postsynaptic potentials (EPSPs)] were frequently recorded. Spontaneous inhibitory postsynaptic potentials were rarely observed except in few cases. Most EPSPs disappeared after injection of lidocaine into the retina. A few EPSPs of small size remained, suggesting that these EPSPs either were from intracranial sources or may have been miniature spontaneous synaptic potentials from retinal ganglion cell axon terminals. Population EPSPs were synchronously evoked by electrical stimulation of the contralateral optic nerve. Their constant onset latency and their ability to follow short-interval paired stimulation indicated that much of the population EPSP's response was monosynaptic. Visually evoked BON spikes and EPSP inputs to BON showed direction sensitivity when a moving pattern was projected onto the entire contralateral retina. With the use of smaller moving patterns, the receptive field of an individual BON cell was identified. A small spot of light, projected within the receptive field, guided the placement of a bipolar stimulation electrode to activate retinal ganglion cells that provided input to that BON cell. EPSPs evoked by this retinal microstimulation showed features of unitary EPSPs. Those EPSPs had distinct low current thresholds. Recruitment of other inputs was only evident when the stimulation level was increased substantially above threshold. The average size of evoked unitary EPSPs was 7.8 mV, confirming the large size of synaptic inputs of this system relative to nonsynaptic noise. EPSP shape was plotted (rise time vs. amplitude), with the use of either evoked unitary EPSPs or spontaneous EPSPs. Unlike samples of spontaneous EPSPs, data from many unitary EPSPs formed distinct clusters in these scatterplots, indicating that these EPSPs had a unique shape among the whole population of EPSPs. In most BON cells studied, hyperpolarization-activated channels caused a slow depolarization sag that reached a plateau within 0.5–1 s. This property suggests that BON cells may be more complicated than a simple site for convergence of direction-sensitive retinal ganglion cells to form a central retinal slip signal for control of oculomotor reflexes.


2003 ◽  
Vol 20 (3) ◽  
pp. 273-283 ◽  
Author(s):  
MATTHIAS OTT ◽  
BRENO BELLINTANI-GUARDIA

Retinal ganglion cells (RGCs) usually increase their dendritic field area with postnatal retinal growth. The mechanisms that regulate the postnatal shape of dendritic arbors in the growing retina are not well understood. Quantitative studies suffer from the difficulty of labeling specific subpopulations of RGCs selectively including their dendritic processes. In this study, we labeled displaced retinal ganglion cells (DGC) that are known to project to the accessory optic system (AOS) in juvenile and adult chameleons by retrograde transport of dextran amines. The complete population of DGCs was quantitatively screened for the effects of postnatal retinal growth on cell morphology, dendritic field coverage, and dendritic arbor size. The adult eye contained 2000 DGCs/retina. This number was already present at birth. The smaller size of the hatchling eye (approximately 1/3 of the adult size) led to higher densities of DGCs. The greatest accumulation of juvenile DGCs (two-fold higher compared to the adult) was found in the periphery of the retina where the greatest surface expansion was observed. DGC dendritic field areas were adjusted proportionally to this expansion in order to maintain a constant dendritic coverage. The increase of dendritic fields was mediated by two putative passive mechanisms: First, an elongation of individual dendrites similar to previous reports of postnatal RGC development in the retina of goldfish and chicks. Second, and more prominent, we observed that neighboring dendrites were pulled apart from each other. This resulted in a looser spacing of the initially tightly packed dendrites of each dendritic arbor. This dispersal of dendrites over a larger area was, due to its passive nature, proportional to the increase of the retinal surface and preserved a constant dendritic coverage irrespective of the animal's age and eye size.


1998 ◽  
Vol 15 (1) ◽  
pp. 161-175 ◽  
Author(s):  
BARRY B. LEE ◽  
JAN KREMERS ◽  
TSAIYAO YEH

We have reinvestigated receptive-field structure of ganglion cells of the macaque parafovea using counterphase modulation of a bipartite field. Receptive fields were mapped with luminance, chromatic, and cone-isolating stimuli. Center sizes of middle (M) and long (L) wavelength cone opponent cells of the parvocellular (PC) pathway were consistent with previous estimates (Gaussian radii of 2–4 min of arc, corresponding to center diameters of 6–12 min of arc). We calculate that a large factor of the enlargement relative to cone radius could be blur due to the eye's natural optics. Maps were consistent with cone selectivity in surround mechanisms, which had radii of 5–8 min of arc. For magnocellular (MC) cells, center size estimates were also consistent with grating measurements from the literature (also Gaussian radii of 2–4 min of arc). The surround mechanism contributing the MC-cell frequency-doubled response to chromatic modulation appears to possess a subunit structure, and we speculate it derives from nonlinear summation of signals from M,L-cone opponent subunits, such as midget bipolar cells.


2012 ◽  
Vol 107 (7) ◽  
pp. 1795-1807 ◽  
Author(s):  
Ilya Buldyrev ◽  
Theresa Puthussery ◽  
W. Rowland Taylor

Different types of retinal ganglion cells represent distinct spatiotemporal filters that respond selectively to specific features in the visual input. Much about the circuitry and synaptic mechanisms that underlie such specificity remains to be determined. This study examines how N-methyl-d-aspartate (NMDA) receptor signaling combines with other excitatory and inhibitory mechanisms to shape the output of small-field OFF brisk-sustained ganglion cells (OFF-BSGCs) in the rabbit retina. We used voltage clamp to separately resolve NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and inhibitory inputs elicited by stimulation of the receptive field center. Three converging circuits were identified. First is a direct glutamatergic input, arising from OFF cone bipolar cells (CBCs), which is mediated by synaptic NMDA and AMPA receptors. The NMDA input was saturated at 10% contrast, whereas the AMPA input increased monotonically up to 60% contrast. We propose that NMDA inputs selectively enhance sensitivity to low contrasts. The OFF bipolar cells, mediating this direct excitatory input, express dendritic kainate (KA) receptors, which are resistant to the nonselective AMPA/KA receptor antagonist, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt (NBQX), but are suppressed by a GluK1- and GluK3-selective antagonist, ( S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxy-thiophene-3-yl-methyl)-5-methylpyrimidine-2,4-dione (UBP-310). The second circuit entails glycinergic crossover inhibition, arising from ON-CBCs and mediated by AII amacrine cells, which modulate glutamate release from the OFF-CBC terminals. The third circuit also comprises glycinergic crossover inhibition, which is driven by the ON pathway; however, this inhibition impinges directly on the OFF-BSGCs and is mediated by an unknown glycinergic amacrine cell that expresses AMPA but not KA receptors.


2007 ◽  
Vol 98 (3) ◽  
pp. 1380-1391 ◽  
Author(s):  
Ronen Segev ◽  
Elad Schneidman ◽  
Joe Goodhouse ◽  
Michael J. Berry

The concerted action of saccades and fixational eye movements are crucial for seeing stationary objects in the visual world. We studied how these eye movements contribute to retinal coding of visual information using the archer fish as a model system. We quantified the animal's ability to distinguish among objects of different sizes and measured its eye movements. We recorded from populations of retinal ganglion cells with a multielectrode array, while presenting visual stimuli matched to the behavioral task. We found that the beginning of fixation, namely the time immediately after the saccade, provided the most visual information about object size, with fixational eye movements, which consist of tremor and drift in the archer fish, yielding only a minor contribution. A simple decoder that combined information from ≤15 ganglion cells could account for the behavior. Our results support the view that saccades impose not just difficulties for the visual system, but also an opportunity for the retina to encode high quality “snapshots” of the environment.


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