scholarly journals Prolonged synaptic currents increase relay neuron firing at the developing retinogeniculate synapse

2014 ◽  
Vol 112 (7) ◽  
pp. 1714-1728 ◽  
Author(s):  
Jessica L. Hauser ◽  
Xiaojin Liu ◽  
Elizabeth Y. Litvina ◽  
Chinfei Chen
Keyword(s):  
Time Course ◽  
Ganglion Cells ◽  
Synapse Elimination ◽  
Neuron Firing ◽  
Fluorescence Measurements ◽  
Relay Neuron ◽  
Presynaptic Calcium ◽  
Asynchronous Release ◽  
Retinogeniculate Synapse ◽  
Relay Neurons

The retinogeniculate synapse, the connection between retinal ganglion cells (RGC) and thalamic relay neurons, undergoes robust changes in connectivity over development. This process of synapse elimination and strengthening of remaining inputs is thought to require synapse specificity. Here we show that glutamate spillover and asynchronous release are prominent features of retinogeniculate synaptic transmission during this period. The immature excitatory postsynaptic currents exhibit a slow decay time course that is sensitive to low-affinity glutamate receptor antagonists and extracellular calcium concentrations, consistent with glutamate spillover. Furthermore, we uncover and characterize a novel, purely spillover-mediated AMPA receptor current from immature relay neurons. The isolation of this current strongly supports the presence of spillover between boutons of different RGCs. In addition, fluorescence measurements of presynaptic calcium transients suggest that prolonged residual calcium contributes to both glutamate spillover and asynchronous release. These data indicate that, during development, far more RGCs contribute to relay neuron firing than would be expected based on predictions from anatomy alone.

scholarly journals Changes in input strength and number are driven by distinct mechanisms at the retinogeniculate synapse

2014 ◽  
Vol 112 (4) ◽  
pp. 942-950 ◽  
Author(s):  
David J. Lin ◽  
Erin Kang ◽  
Chinfei Chen
Keyword(s):  
Critical Period ◽  
Visual Experience ◽  
Ganglion Cells ◽  
Visual Deprivation ◽  
Homeostatic Plasticity ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Relay Neuron ◽  
Retinogeniculate Synapse ◽  
Dorsal Lateral Geniculate ◽  
Relay Neurons

Recent studies have demonstrated that vision influences the functional remodeling of the mouse retinogeniculate synapse, the connection between retinal ganglion cells and thalamic relay neurons in the dorsal lateral geniculate nucleus (LGN). Initially, each relay neuron receives a large number of weak retinal inputs. Over a 2- to 3-wk developmental window, the majority of these inputs are eliminated, and the remaining inputs are strengthened. This period of refinement is followed by a critical period when visual experience changes the strength and connectivity of the retinogeniculate synapse. Visual deprivation of mice by dark rearing from postnatal day (P)20 results in a dramatic weakening of synaptic strength and recruitment of additional inputs. In the present study we asked whether experience-dependent plasticity at the retinogeniculate synapse represents a homeostatic response to changing visual environment. We found that visual experience starting at P20 following visual deprivation from birth results in weakening of existing retinal inputs onto relay neurons without significant changes in input number, consistent with homeostatic synaptic scaling of retinal inputs. On the other hand, the recruitment of new inputs to the retinogeniculate synapse requires previous visual experience prior to the critical period. Taken together, these findings suggest that diverse forms of homeostatic plasticity drive experience-dependent remodeling at the retinogeniculate synapse.

scholarly journals Metabotropic glutamate receptors and glutamate transporters shape transmission at the developing retinogeniculate synapse

2013 ◽  
Vol 109 (1) ◽  
pp. 113-123 ◽  
Author(s):  
Jessica L. Hauser ◽  
Eleanore B. Edson ◽  
Bryan M. Hooks ◽  
Chinfei Chen
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Time Course ◽  
Ganglion Cells ◽  
Glutamate Transporters ◽  
Decay Kinetics ◽  
Metabotropic Glutamate ◽  
Glutamate Concentration ◽  
Group Ii ◽  
Retinogeniculate Synapse

Over the first few postnatal weeks, extensive remodeling occurs at the developing murine retinogeniculate synapse, the connection between retinal ganglion cells (RGCs) and the visual thalamus. Although numerous studies have described the role of activity in the refinement of this connection, little is known about the mechanisms that regulate glutamate concentration at and around the synapse over development. Here we show that interactions between glutamate transporters and metabotropic glutamate receptors (mGluRs) dynamically control the peak and time course of the excitatory postsynaptic current (EPSC) at the immature synapse. Inhibiting glutamate transporters by bath application of TBOA (dl- threo-β-benzyloxyaspartic acid) prolonged the decay kinetics of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) currents at all ages. Moreover, at the immature synapse, TBOA-induced increases in glutamate concentration led to the activation of group II/III mGluRs and a subsequent reduction in neurotransmitter release at RGC terminals. Inhibition of this negative-feedback mechanism resulted in a small but significant increase in peak NMDAR EPSCs during basal stimulation and a substantial increase in the peak with coapplication of TBOA. Activation of mGluRs also shaped the synaptic response during high-frequency trains of stimulation that mimic spontaneous RGC activity. At the mature synapse, however, the group II mGluRs and the group III mGluR7-mediated response are downregulated. Our results suggest that transporters reduce spillover of glutamate, shielding NMDARs and mGluRs from the neurotransmitter. Furthermore, mechanisms of glutamate clearance and release interact dynamically to control the glutamate transient at the developing retinogeniculate synapse.

scholarly journals Retinogeniculate Synaptic Properties Controlling Spike Number and Timing in Relay Neurons

2003 ◽  
Vol 90 (4) ◽  
pp. 2438-2450 ◽  
Author(s):  
Dawn M. Blitz ◽  
Wade G. Regehr
Keyword(s):  
Ganglion Cells ◽  
Brain Slices ◽  
Visual Signals ◽  
Dynamic Clamp ◽  
Neuron Spike ◽  
Relay Neuron ◽  
Nmda Current ◽  
Spike Number ◽  
Low Threshold ◽  
Relay Neurons

Retinal ganglion cells (RGC) transmit visual signals to thalamocortical relay neurons in the lateral geniculate nucleus via retinogeniculate synapses. Relay neuron spike patterns do not simply reflect those of RGCs, but the mechanisms controlling this transformation are not well understood. We therefore examined synaptic properties controlling the strength and precision of relay neuron firing in mouse (p28–33) brain slices using physiological stimulation patterns and a combination of current clamp and dynamic clamp. In tonic mode (-55 mV), activation of single RGC inputs elicited stereotyped responses in a given neuron. In contrast, responses in different neurons varied from unreliable, to faithfully following, to a gain in the number of spikes. Dynamic clamp experiments indicated these different responses primarily reflected variability in the amplitudes of the N-methyl-d-aspartate (NMDA) and AMPA components. Each of these components played a distinct role in transmission. The AMPA component evoked a single precisely timed, short-latency spike per stimulus, but efficacy decreased during repetitive stimulation due to desensitization and depression. The NMDA component elicited longer-latency spikes and multiple spikes per stimulus and became more effective during repetitive stimuli that led to NMDA current summation. We found that in burst mode (–75 mV), where low-threshold calcium spikes are activated, AMPA and NMDA components and synaptic plasticity influenced spike number, but no combination enabled relay cells to faithfully follow the stimulus. Thus the characteristics of AMPA and NMDA currents, the ratio of these currents and use-dependent plasticity interact to shape how RGC activity is conveyed to relay neurons.

Different Roles for AMPA and NMDA Receptors in Transmission at the Immature Retinogeniculate Synapse

2008 ◽  
Vol 99 (2) ◽  
pp. 629-643 ◽  
Author(s):  
Xiaojin Liu ◽  
Chinfei Chen
Keyword(s):  
Visual Cortex ◽  
Time Course ◽  
Retinal Ganglion ◽  
Current Time ◽  
Temporal Precision ◽  
Relay Neuron ◽  
Ampa And Nmda Receptors ◽  
Eye Opening ◽  
Retinogeniculate Synapse ◽  
Spike Latency

The relay of information at the retinogeniculate synapse, the connection between retina and visual thalamus, begins days before eye opening and is thought to play an important role in the maturation of neural circuits in the thalamus and visual cortex. Remarkably, during this period of development, the retinogeniculate synapse is immature, with single retinal ganglion cell inputs evoking an average peak excitatory postsynaptic current (EPSC) of only about 40 pA compared with 800 pA in mature synapses. Yet, at the mature synapse, EPSCs >400 pA are needed to drive relay neuron firing. This raises the question of how small-amplitude EPSCs can drive transmission at the immature retinogeniculate synapse. Here we find that several features of the immature synapse, compared with the mature synapse, contribute to synaptic transmission. First, although the peak amplitude of EPSC is small, the decay time course of both α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) currents is significantly slower. The prolonged time course of NMDAR currents is a result of the presence of both NR2B and NR2C/D subunits. In addition, the extended presence of neurotransmitter released prolongs the synaptic current time course. Second, reduced sensitivity to magnesium block results in significantly greater synaptic charge transfer through NMDAR. Third, AMPAR currents contribute to the spike latency, but not to temporal precision, at the immature synapse. Furthermore, intrinsic excitability is greater. These properties enable immature synapses with predominantly NMDARs and little or no AMPARs to contribute to the relay of information from retina to visual cortex.

scholarly journals Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Biji Mathew ◽  
Leianne A. Torres ◽  
Lorea Gamboa Gamboa Acha ◽  
Sophie Tran ◽  
Alice Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Time Course ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Paracrine Effects

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

Dendritic competition in the developing retina: Ganglion cell density gradients and laterally displaced dendrites

1993 ◽  
Vol 10 (2) ◽  
pp. 313-324 ◽  
Author(s):  
Rafael Linden
Keyword(s):  
Density Gradient ◽  
Cell Density ◽  
Time Course ◽  
Ganglion Cells ◽  
Lateral Displacement ◽  
Optic Tract ◽  
Density Gradients ◽  
Temporal Asymmetry ◽  
Dendritic Arbors ◽  
Contralateral Eye

AbstractDendrites of retinal ganglion cells (RGCs) tend to be distributed preferentially toward areas of reduced RGC density. This, however, does not occur in the retina of normal pigmented rats, in which it has been suggested that the centro-peripheral gradient of RGC density is too shallow to provide directional guidance to growing dendrites. In this study, laterally displaced dendrites of RGCs retrogradely labeled with horseradish peroxidase were related to cell density gradients induced experimentally in the rat retina. Neonatal unilateral lesions of the optic tract produced retrograde degeneration of contralaterally projecting RGCs, but spared ipsilaterally projecting neurons in the same retina. These lesions created an anomalous temporal to nasal gradient of cell density across the decussation line, opposite to the nasal to temporal gradient found along the same axis in either normal rats or rats that had the contralateral eye removed at birth. RGCs in rats that received optic tract lesions had their dendrites displaced laterally toward the depleted nasal retina, while in either normal or enucleated rats there was no naso-temporal asymmetry. The lateral displacement affected both primary dendrites and higher-order branches. However, the gradient of cell density after optic tract lesions was less steep than the gradient in either normal or enucleated rats. To test for the presence of steeper gradients at early stages of development, RGC density gradients were also examined at postnatal day 5 (P5). In normal rats, the RGCs were homogeneously distributed throughout the retina, while rats given optic tract lesions at birth already showed a temporo-nasal density gradient at P5. Still, this anomalous gradient was less steep than that found in normal adults. It is concluded that the time course, rather than the steepness of the RGC density gradient, is the major determinant of the lateral displacement of dendritic arbors with respect to the soma in developing RGCs. The data are consistent with the idea that the overall shape of dendritic arbors depends in part on dendritic competition during retinal development.

Bullfrog dorsal root ganglion cells having tetrodotoxin-resistant spikes are endowed with nicotinic receptors

1989 ◽  
Vol 62 (3) ◽  
pp. 657-664 ◽  
Author(s):  
K. Morita ◽  
Y. Katayama
Keyword(s):  
Dorsal Root Ganglion ◽  
Conduction Velocity ◽  
Dorsal Root ◽  
Time Course ◽  
Ganglion Cells ◽  
Reversal Potential ◽  
Membrane Resistance ◽  
Fast Response ◽  
Dorsal Root Ganglion Cells

1. Intracellular recordings were made from bullfrog dorsal root ganglion (DRG) neurons in vitro. They were divided into three types, As, Ar, and C, according to their conduction velocity and their sensitivity to tetrodotoxin [TTX (less than or equal to 1 microM)]; an As neuron had a fast conduction velocity (13-50 m/s, mean = 31 m/s, n = 73) and TTX-sensitive sodium soma spikes: an Ar neuron showed a fast conduction velocity (4-28 m/s, mean = 14 m/s, n = 52) and TTX-resistant sodium soma spikes; and a C neuron had a slow conduction velocity (0.16-0.8 m/s, mean = 0.4 m/s, n = 49) and TTX-resistant sodium-calcium soma spikes. 2. Superfusion of acetylcholine [ACh (0.3 microM-1 mM)] produced a fast depolarization in 70% of Ar and in 50% of C neurons. No As neuron showed a fast depolarization in response to ACh. The ACh-induced fast response persisted in calcium-free or TTX-containing solutions. 3. The response in both Ar and C neurons was similar except in time course; the response was always more rapid in C than in Ar neurons. The response was always associated with a decreased membrane resistance and reversed in polarity at about -30 mV. The reversal potential varied with both sodium and potassium concentrations of the superfusing solutions. 4. Nicotine, (+)-tubocurarine [(+)-TC], and hexamethonium reversibly blocked the ACh fast response.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphology of cells in the ganglion cell layer during development of the rat retina

1980 ◽  
Vol 208 (1173) ◽  
pp. 433-446 ◽  
Keyword(s):  
Ganglion Cell ◽  
Time Course ◽  
Ganglion Cell Layer ◽  
Ganglion Cells ◽  
Cell Layer ◽  
Type I ◽  
Adult Size ◽  
Rat Retina ◽  
Adult Rat ◽  
Dendritic Fields

The development of the cells in the ganglion cell layer in the rat retina has been studied from 3 to 30 days of age postnatal by means of Golgi-stained whole-mounted retinae. The retina grows rapidly from birth to ten days of age and then more slowly from 10 to 30 days of age. The different classes of ganglion cell can be clearly recognized by 10 days of age, but type I ganglion cells with a size comparable to those found in the adult rat retina are not seen until thirty days of age. Type II cells may attain their adult size before type I cells do. The growth of the retina and the resulting decrease in cell density in the ganglion cell layer occur with the same time course as the increase in the size of the cell soma and their dendritic fields.

scholarly journals Synaptic inputs to the ganglion cells in the tiger salamander retina.

1979 ◽  
Vol 73 (3) ◽  
pp. 265-286 ◽  
Author(s):  
D F Wunk ◽  
F S Werblin
Keyword(s):  
Cell Membrane ◽  
Receptive Field ◽  
Ganglion Cell ◽  
Time Course ◽  
Ganglion Cells ◽  
Hybrid Cell ◽  
Amacrine Cells ◽  
Inhibitory Input ◽  
Tiger Salamander ◽  
Synaptic Inputs

The postsynaptic potentials (PSPs) that form the ganglion cell light response were isolated by polarizing the cell membrane with extrinsic currents while stimulating at either the center or surround of the cell's receptive field. The time-course and receptive field properties of the PSPs were correlated with those of the bipolar and amacrine cells. The tiger salamander retina contains four main types of ganglion cell: "on" center, "off" center, "on-off", and a "hybrid" cell that responds transiently to center, but sustainedly, to surround illumination. The results lead to these inferences. The on-ganglion cell receives excitatory synpatic input from the on bipolars and that synapse is "silent" in the dark. The off-ganglion cell receives excitatory synaptic input from the off bipolars with this synapse tonically active in the dark. The on-off and hybrid ganglion cells receive a transient excitatory input with narrow receptive field, not simply correlated with the activity of any presynaptic cell. All cell types receive a broad field transient inhibitory input, which apparently originates in the transient amacrine cells. Thus, most, but not all, ganglion cell responses can be explained in terms of synaptic inputs from bipolar and amacrine cells, integrated at the ganglion cell membrane.

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