scholarly journals Channeling Vision: CaV1.4—A Critical Link in Retinal Signal Transmission

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
D. M. Waldner ◽  
N. T. Bech-Hansen ◽  
W. K. Stell

Voltage-gated calcium channels (VGCC) are key to many biological functions. Entry of Ca2+into cells is essential for initiating or modulating important processes such as secretion, cell motility, and gene transcription. In the retina and other neural tissues, one of the major roles of Ca2+-entry is to stimulate or regulate exocytosis of synaptic vesicles, without which synaptic transmission is impaired. This review will address the special properties of one L-type VGCC,CaV1.4, with particular emphasis on its role in transmission of visual signals from rod and cone photoreceptors (hereafter called “photoreceptors,” to the exclusion of intrinsically photoreceptive retinal ganglion cells) to the second-order retinal neurons, and the pathological effects of mutations in theCACNA1Fgene which codes for the pore-formingα1Fsubunit ofCaV1.4.

2021 ◽  
Vol 67 (3) ◽  
pp. 10-16
Author(s):  
H.V. Dumanska ◽  
◽  
O.V. Rikchalsky ◽  
N.S. Veselovsky ◽  
◽  
...  

We investigated the changes in distribution of the NMDA- and AMPA-receptors in the synapses in the in vitro model of the retinocollicular pathway. The model was a primary coculture of the retinal cells and superficial superior colliculus (SSC) neurons. Evoked postsynaptic currents (ePSCs) were recorded in SSC neurons in response to local electrical extracellular stimulation of the afferent retinal ganglion cells’ (RGC) axons. We analyzed the changes in the kinetic characteristics of ePSCs at different holding potentials during cocultivation. The results obtained reflect that NMDA receptors play an essential role in the formation of the retinocollicular synapses. After the formation of retinocollicular connections, the main role in the sensory signal transmission belongs to AMPA receptors. Thus, the data obtained indicate the specific dynamic changes of the functional roles of NMDA- and AMPA-receptors in the forma- tion and development of the retinocollicular synaptic contacts.


1998 ◽  
Vol 80 (4) ◽  
pp. 1752-1764 ◽  
Author(s):  
Fan Gao ◽  
Samuel M. Wu

Gao, Fan and Samuel M. Wu. Characterization of spontaneous inhibitory synaptic currents in salamander retinal ganglion cells. J. Neurophysiol. 80: 1752–1764, 1998. Spontaneous and light-evoked postsynaptic currents (sPSCs and lePSCs, respectively) in retinal ganglion cells of the larval tiger salamander were recorded under voltage-clamp conditions from living retinal slices. The focus of this study is to characterize the spontaneous inhibitory PSCs (sIPSCs) and their contribution to the light-evoked inhibitory PSCs (leIPSCs) in on-off ganglion cells. sIPSCs were isolated from spontaneous excitatory PSCs (sEPSCs) by application of 10 μM 6,7-dinitroquinoxaline-2,3-dione (DNQX) + 50 μM 2-amino-5-phosphonopentanoic acid (AP5). In ∼70% of on-off ganglion cells, bicuculline (or picrotoxin) completely blocks sIPSCs, suggesting all sIPSCs in these cells are mediated by GABAergic synaptic vesicles and γ-aminobutyric acid-A (GABAA) receptors (GABAergic sIPSCs, or GABAsIPSCs). In the remaining 30% of on-off ganglion cells, bicuculline (or picrotoxin) blocks 70–98% of the sIPSCs, and the remaining 2–30% are blocked by strychnine (glycinergic sIPSCs, or GLYsIPSCs). GABAsIPSCs occur randomly with an exponentially distributed interval probability density function, and they persist without noticeable rundown over time. The GABAsIPSC frequency is greatly reduced by cobalt, consistent with the idea that they are largely mediated by calcium-dependent vesicular release. GABAsIPSCs in DNQX + AP5 are tetrodotoxin (TTX) insensitive, suggesting that amacrine cells that release GABA under these conditions do not generate spontaneous action potentials. The average GABAsIPSCs exhibited linear current-voltage relation with a reversal potential near the chloride equilibrium potential, and an average peak conductance of 319.67 ± 252.83 (SD) pS. For GLYsIPSCs, the average peak conductance increase is 301.68 ± 94.34 pS. These parameters are of the same order of magnitude as those measured in inhibitory miniature postsynaptic currents (mIPSCs) associated with single synaptic vesicles in the CNS. The amplitude histograms of GABAsIPSCs did not exhibit multiple peaks, suggesting that the larger events are not discrete multiples of elementary events (or quanta). We propose that each GABAsIPSC or GLYsIPSC in retinal ganglion cells is mediated by a single or synchronized multiple of synaptic vesicles with variable neurotransmitter contents. In a sample of 16 on-off ganglion cells, the average peak leIPSC (held at 0 mV) at the light onset is 509.0 ± 233.85 pA and that at the light offset is 529.0 ± 339.88 pA. The approximate number of GABAsIPSCs and GLYsIPSCs required to generate the average light responses, calculated by the ratio of the charge (area under current traces) of the leIPSCs to that of the average single sIPSCs, is 118 ± 52 for the light onset, and 132 ± 76 for the light offset.


2016 ◽  
Vol 113 (21) ◽  
pp. 6047-6052 ◽  
Author(s):  
Diego Carlos Fernandez ◽  
Yi-Ting Chang ◽  
Samer Hattar ◽  
Shih-Kuo Chen

The suprachiasmatic nucleus (SCN) receives direct retinal input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) for circadian photoentrainment. Interestingly, the SCN is the only brain region that receives equal inputs from the left and right eyes. Despite morphological assessments showing that axonal fibers originating from ipRGCs cover the entire SCN, physiological evidence suggests that only vasoactive intestinal polypeptide (VIP)/gastrin-releasing peptide (GRP) cells located ventrally in the SCN receive retinal input. It is still unclear, therefore, which subpopulation of SCN neurons receives synaptic input from the retina and how the SCN receives equal inputs from both eyes. Here, using single ipRGC axonal tracing and a confocal microscopic analysis in mice, we show that ipRGCs have elaborate innervation patterns throughout the entire SCN. Unlike conventional retinal ganglion cells (RGCs) that innervate visual targets either ipsilaterally or contralaterally, a single ipRGC can bilaterally innervate the SCN. ipRGCs form synaptic contacts with major peptidergic cells of the SCN, including VIP, GRP, and arginine vasopressin (AVP) neurons, with each ipRGC innervating specific subdomains of the SCN. Furthermore, a single SCN-projecting ipRGC can send collateral inputs to many other brain regions. However, the size and complexity of the axonal arborizations in non-SCN regions are less elaborate than those in the SCN. Our results provide a better understanding of how retinal neurons connect to the central circadian pacemaker to synchronize endogenous circadian clocks with the solar day.


2016 ◽  
Vol 215 (2) ◽  
pp. 147-149 ◽  
Author(s):  
Jeremy N. Kay

Newborn neuron radial migration is a key force shaping the nervous system. In this issue, Icha et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201604095) use zebrafish retinal ganglion cells as a model to investigate the cell biological basis of radial migration and the consequences for retinal histogenesis when migration is impaired.


2018 ◽  
Author(s):  
Quentin Lo Giudice ◽  
Marion Leleu ◽  
Pierre J. Fabre

ABSTRACTRetinal ganglion cells (RGC), together with cone photoreceptors, horizontal cells (HC) and amacrine cells (AC), are the first classes of neurons produced in the retina. Here we have profiled 5348 single retinal cells and provided a comprehensive transcriptomic atlas showing the broad diversity of the developing retina at the time when the four early-born cells are being produced. Our results show the transcriptional sequences that establish the hierarchical ordering of early cell fate specification in the retina. RGC maturation follows six waves of gene expression, giving new insight into the regulatory logic of RGC differentiation. Early-generated RGCs transcribe an increasing amount of guidance cues for young peripheral RGC axons that express the matching receptors. Finally, spatial signatures in sub-populations of RGCs allowed to define novel molecular markers that are spatially restricted during the development of the retina. Altogether this study is a valuable resource that identifies new players in mouse retinal development, shedding light on transcription factors sequence and guidance cues dynamics in space and time.


2018 ◽  
Author(s):  
Victoria H. Fan ◽  
Lauren E. Grosberg ◽  
Sasidhar S. Madugula ◽  
Pawel Hottowy ◽  
Wladyslaw Dabrowski ◽  
...  

AbstractObjectiveEpiretinal prostheses are designed to restore vision in people blinded by photoreceptor degenerative diseases, by directly activating retinal ganglion cells (RGCs) using an electrode array implanted on the retina. In present-day clinical devices, current spread from the stimulating electrode to a distant return electrode often results in the activation of many cells, potentially limiting the quality of artificial vision. In the laboratory, epiretinal activation of RGCs with cellular resolution has been demonstrated with small electrodes, but distant returns may still cause undesirable current spread. Here, the ability of local return stimulation to improve the selective activation of RGCs at cellular resolution was evaluated.ApproachA custom multi-electrode array (512 electrodes, 10 μm diameter, 60 μm pitch) was used to simultaneously stimulate and record from RGCs in isolated primate retina. Stimulation near the RGC soma with a single electrode and a distant return was compared to stimulation in which the return was provided by six neighboring electrodes.Main resultsLocal return stimulation enhanced the capability to activate cells near the central electrode (<30 μm) while avoiding cells farther away (>30 μm). This resulted in an improved ability to selectively activate ON and OFF cells, including cells encoding immediately adjacent regions in the visual field.SignificanceThese results suggest that a device that restricts the electric field through local returns could optimize activation of neurons at cellular resolution, improving the quality of artificial vision.Novelty & SignificanceThe effectiveness of local return stimulation for enhancing the electrical activation of retinal neurons was tested using high-density multi-electrode recording and stimulation in isolated macaque retina. The results suggest that local returns may reduce unwanted evoked activity and thus optimize the selectivity of stimulation at cellular resolution. Similar patterns could be implemented in a future high-resolution prosthesis to permit a more faithful replication of normal retinal activity for the treatment of incurable blindness.


2017 ◽  
Author(s):  
Aboozar Monavarfeshani ◽  
Gail Stanton ◽  
Jonathan Van Name ◽  
Kaiwen Su ◽  
William A. Mills ◽  
...  

AbstractIt has long been thought that the mammalian visual system is organized into parallel pathways, with incoming visual signals being parsed in the retina based on feature (e.g. color, contrast and motion) and then transmitted to the brain in unmixed, feature-specific channels. To faithfully convey feature-specific information from retina to cortex, thalamic relay cells must receive inputs from only a small number of functionally similar retinal ganglion cells. However, recent studies challenged this by revealing substantial levels of retinal convergence onto relay cells. Here, we sought to identify mechanisms responsible for the assembly of such convergence. Using an unbiased transcriptomics approach and targeted mutant mice, we discovered a critical role for the synaptic adhesion molecule Leucine Rich Repeat Transmembrane Neuronal 1 (LRRTM1) in the emergence of retinothalamic convergence. Importantly, LRRTM1 mutant mice display impairment in visual behaviors, suggesting a functional role of retinothalamic convergence in vision.


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