scholarly journals Effects of intravitreal injection of a Rho-GTPase inhibitor (BA-210), or CNTF combined with an analogue of cAMP, on the dendritic morphology of regenerating retinal ganglion cells

2014 ◽  
Vol 32 (3) ◽  
pp. 391-402 ◽  
Author(s):  
Eleanor S. Drummond ◽  
Jennifer Rodger ◽  
Marissa Penrose ◽  
Donald Robertson ◽  
Ying Hu ◽  
...  
Keyword(s):  
Intravitreal Injection ◽  
Retinal Ganglion Cells ◽  
Rho Gtpase ◽  
Ganglion Cells ◽  
Dendritic Morphology ◽  
Retinal Ganglion

scholarly journals The Endothelin Receptor Antagonist Macitentan Ameliorates Endothelin-Mediated Vasoconstriction and Promotes Neuroprotection of Retinal Ganglion Cells in Rats

2020 ◽  
Author(s):  
Dorota L. Stankowska ◽  
Wei Zhang ◽  
Shaoqing He ◽  
Vignesh R. Krishnamoorthy ◽  
Payton Harris ◽  
...  
Keyword(s):  
Body Weight ◽  
Receptor Antagonist ◽  
Intravitreal Injection ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Endothelin Receptor Antagonist ◽  
Brown Norway ◽  
Retinal Ganglion ◽  
Endothelin Receptor ◽  
Norway Rats

AbstractPurposeTo determine if dietary administration of the dual ETA/ ETB receptor antagonist, macitentan, could protect retinal ganglion cells (RGCs) following endothelin-1 (ET-1) mediated vasoconstriction in Brown Norway rats.MethodsAdult male and female Brown Norway rats were either untreated or treated with macitentan (5 mg/kg body weight) once a day for 3 days followed by intravitreal injection of either 4 μl of 500 μM ET-1 (2 nmole/eye) or vehicle in one eye. Imaging of the retinal vasculature using fluorescein angiography was carried out at various time points, including, 5, 10, 15, 25 and 30 minutes. Following the imaging of the vasculature, rats were either treated with macitentan (5 mg/kg/body weight in dietary gels) or untreated (control gels without medication). Following treatments, rats were euthanized, retinal flat mounts were prepared, immunostained for RGC marker Brn3a, imaged and surviving RGCs were counted in a masked manner.ResultsVasoconstrictive effects following intravitreal ET-1 injection were greatly reduced in rats administered with macitentan in the diet prior to the ET-1 administration. ET-1 intravitreal injection produced a 31% loss of RGCs which was significantly reduced in macitentan-treated rats. Following ET-1 administration, GFAP immunostaining was increased in the ganglion cell layer as well as in the retrolaminar region, suggestive of astrocytic activation by ET-1 administration. RGC numbers in macitentan treated and ET-1 injected rats were similar to that observed in control retinas.ConclusionsET-1-mediated neurodegeneration could occur through both vascular and cellular mechanisms. The endothelin receptor antagonist, macitentan, has neuroprotective effects in retinas of Brown Norway rats that occurs through different mechanisms, including, enhancement of RGC survival and reduction ET-1 mediated vasoconstriction.

scholarly journals Type-specific dendritic integration in mouse retinal ganglion cells

2019 ◽  
Author(s):  
Yanli Ran ◽  
Ziwei Huang ◽  
Tom Baden ◽  
Harald Baayen ◽  
Philipp Berens ◽  
...  
Keyword(s):  
Ion Channel ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Receptive Fields ◽  
Temporal Correlation ◽  
Dendritic Morphology ◽  
Membrane Properties ◽  
Retinal Ganglion ◽  
Dendritic Integration ◽  
Dendritic Arbour

ABSTRACTNeural computation relies on the integration of synaptic inputs across a neuron’s dendritic arbour. However, the fundamental rules that govern dendritic integration are far from understood. In particular, it is still unclear how cell type-specific differences in dendritic integration arise from general features of neural morphology and membrane properties. Here, retinal ganglion cells (RGCs), which relay the visual system’s first computations to the brain, represent an exquisite model. They are functionally and morphologically diverse yet defined, and they allow studying dendritic integration in a functionally relevant context. Here, we show how four morphologically distinct types of mouse RGC with shared excitatory synaptic input (transient Off alpha, transient Off mini, sustained Off, and F-miniOff) exhibit distinct dendritic integration rules. Using two-photon imaging of dendritic calcium signals and biophysical modelling, we demonstrate that these RGC types strongly differ in their spatio-temporal dendritic integration: In transient Off alpha cells, dendritic receptive fields displayed little spatial overlap, indicative of a dendritic arbour that is partitioned in largely isolated regions. In contrast, dendritic receptive fields in the other three RGCs overlapped greatly and were offset to the soma, suggesting strong synchronization of dendritic signals likely due to backpropagation of somatic signals. Also temporal correlation of dendritic signals varied extensively among these types, with transient Off mini cells displaying the highest correlation across their dendritic arbour. Modelling suggests that morphology alone cannot explain these differences in dendritic integration, but instead specific combinations of dendritic morphology and ion channel densities are required. Together, our results reveal how neurons exhibit distinct dendritic integration profiles tuned towards their type-specific computations in their circuits, with the interplay between morphology and ion channel complement as a key contributor.

Impulse Encoding Across the Dendritic Morphologies of Retinal Ganglion Cells

1999 ◽  
Vol 81 (4) ◽  
pp. 1685-1698 ◽  
Author(s):  
Brent W. Sheasby ◽  
Jurgen F. Fohlmeister
Keyword(s):  
Frequency Response ◽  
Surface Area ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Dendritic Morphology ◽  
Retinal Ganglion ◽  
Impulse Frequency ◽  
Data Set ◽  
Tree Structures ◽  
Membrane Area

Impulse encoding across the dendritic morphologies of retinal ganglion cells. Nerve impulse entrainment and other excitation and passive phenomena are analyzed for a morphologically diverse and exhaustive data set ( n = 57) of realistic (3-dimensional computer traced) soma-dendritic tree structures of ganglion cells in the tiger salamander ( Ambystoma tigrinum) retina. The neurons, including axon and an anatomically specialized thin axonal segment that is observed in every ganglion cell, were supplied with five voltage- or ligand-gated ion channels (plus leakage), which were distributed in accordance with those found in a recent study that employed an equivalent dendritic cylinder. A wide variety of impulse-entrainment responses was observed, including regular low-frequency firing, impulse doublets, and more complex patterns involving impulse propagation failures (or aborted spikes) within the encoder region, all of which have been observed experimentally. The impulse-frequency response curves of the cells fell into three groups called fast, medium, andslow in approximate proportion as seen experimentally. In addition to these, a new group was found among the traced cells that exhibited an impulse-frequency response twice that of thefast category. The total amount of soma-dendritic surface area exhibited by a given cell is decisive in determining its electrophysiological classification. On the other hand, we found only a weak correlation between the electrophysiological group and the morphological classification of a given cell, which is based on the complexity of dendritic branching and the physical reach or “receptive field” area of the cell. Dendritic morphology determines discharge patterns to dendritic (synaptic) stimulation. Orthodromic impulses can be initiated on the axon hillock, the thin axonal segment, the soma, or even the proximal axon beyond the thin segment, depending on stimulus magnitude, soma-dendritic membrane area, channel distribution, and state within the repetitive impulse cycle. Although a sufficiently high dendritic Na-channel density can lead to dendritic impulse initiation, this does not occur with our “standard” channel densities and is not seen experimentally. Even so, impulses initiated elsewhere do invade all except very thin dendritic processes. Impulse-encoding irregularities increase when channel conductances are reduced in the encoder region, and the F/I properties of the cells are a strong function of the calcium- and Ca-activated K-channel densities. Use of equivalent dendritic cylinders requires more soma-dendritic surface area than real dendritic trees, and the source of the discrepancy is discussed.

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