Pharmacological studies of the mouse cone electroretinogram

2005 ◽  
Vol 22 (5) ◽  
pp. 631-636 ◽  
Author(s):  
SUMIT SHARMA ◽  
SHERRY L. BALL ◽  
NEAL S. PEACHEY
Keyword(s):  
Cell Activity ◽  
Retinal Disease ◽  
Experimental Treatment ◽  
Receptor Activation ◽  
Bipolar Cells ◽  
Small Contribution ◽  
Hereditary Retinal Disease ◽  
Cone Pathway ◽  
Pharmacological Studies ◽  
Species Activity

Electroretinography provides a useful noninvasive approach to evaluate cone pathway activity. Despite wide application of the cone ERG to characterize retinal function in transgenic mice and mouse models of human hereditary retinal disease, the cellular origins of the mouse cone ERG have not been well defined. Here, we address this issue using a pharmacological approach that has been previously applied to other species. Agents that block receptor activation at well-defined retinal loci were dissolved in saline and injected into the vitreous of anesthetized adult BALBc/ByJ mice; cone ERGs were recorded 1–2 h later. Analysis of the resulting waveforms indicated that the mouse cone ERG includes a cornea-negative component that is derived from the activity of cone photoreceptors and retinal glial (Müller) cells. Similar to other species, activity of cone depolarizing bipolar cells contributes a large amplitude cornea-positive potential to the mouse cone ERG. In contrast to primate but similar to rat, the mouse cone ERG includes only a small contribution from hyperpolarizing bipolar cell activity. The inner retina appears to contribute to both thea- andb-waves of the mouse cone ERG. These results provide a foundation for interpreting changes in the waveform of the mouse cone ERG that may be observed following genetic alteration or other experimental treatment.

Pharmacological analysis of the rat cone electroretinogram

2003 ◽  
Vol 20 (3) ◽  
pp. 297-306 ◽  
Author(s):  
LI XU ◽  
SHERRY L. BALL ◽  
KENNETH R. ALEXANDER ◽  
NEAL S. PEACHEY
Keyword(s):  
Retinal Disease ◽  
Experimental Treatment ◽  
Negative Polarity ◽  
Bipolar Cells ◽  
Sprague Dawley ◽  
Negative Wave ◽  
Sprague Dawley Rats ◽  
Amplitude Component ◽  
Cone System ◽  
Depolarizing Bipolar Cell

The electroretinogram (ERG) of the cone system provides a useful noninvasive measure of the activity of the cone pathway. Despite a wide application of the cone ERG in the study of rodent models of human hereditary retinal disease, the cellular origins of the rat cone ERG have not been well defined. Here, we address this issue using a pharmacological approach that has been used previously to derive ERG response components. Agents that impair synaptic transmission at well-defined retinal loci were dissolved in saline and injected into the vitreous of adult Sprague-Dawley rats anesthetized with ketamine/xylazine, and cone ERGs were recorded approximately 2 h later. Analysis of the resulting waveforms indicated that the rat cone ERG includes a relatively small-amplitude component of negative polarity that is derived from the activity of cone photoreceptors, and perhaps retinal glial (Müller) cells. The cone depolarizing bipolar cell pathway contributes a positive potential of large amplitude to the rat cone ERG. In comparison, the contribution of hyperpolarizing bipolar cells is of negative polarity and of much smaller amplitude. The inner retina contributes a negative wave upon which higher frequency oscillations are superimposed. These results provide a foundation for interpreting changes in the waveform of the rat cone ERG that may be observed following genetic alteration or other experimental treatment.

Primate Retinal Signaling Pathways: Suppressing on-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-NYX Genetic Night Blindness

2005 ◽  
Vol 93 (1) ◽  
pp. 481-492 ◽  
Author(s):  
Naheed W. Khan ◽  
Mineo Kondo ◽  
Kelaginamane T. Hiriyanna ◽  
Jeff A. Jamison ◽  
Ronald A. Bush ◽  
...  
Keyword(s):  
Night Blindness ◽  
Cell Activity ◽  
Drug Application ◽  
Bipolar Cells ◽  
Gene Encoding ◽  
Light Responses ◽  
Pathway Activity ◽  
Cone Pathway ◽  
Glutamate Analogues ◽  
Human Primate

Retinal on-pathway dysfunction is implicated in human complete-type congenital stationary night blindness (CSNB1), a Mendelian genetic condition that results from mutations in the NYX gene encoding the protein nyctalopin. We probed cone pathway dysfunction in four human genotyped CSNB1 affected males by electroretinogram (ERG) recordings elicited with photopic sinusoidal and rapid-on/off-ramp flicker stimuli that are reputed to elicit on/off-pathway activity selectively. Results were analyzed in relation to ERG abnormalities created in anesthetized non-human primates by intravitreal application of glutamate analogues that selectively suppress retinal on- or off-pathway bipolar cell activity. 2-amino-4-phosphonobutyric acid (APB), which selectively blocks light responses of on-pathway depolarizing bipolar cells, fully recreated the essential ERG abnormalities found for human CSNB1 under the condition that the off-pathway remained active. Both CSNB1- NYX humans and APB-treated monkey retina lacked the normal amplitude dip and the phase deflection that occurs in the fundamental component near 12 Hz for sinusoidal flicker stimuli. The off-pathway suppressing agent, cis-2,3-piperidine-dicarboxylic acid (PDA), gave results in monkey quite discordant to CSNB1 human for sinusoidal stimulation. The results implicated a specific on-pathway signaling deficiency in CSNB1- NYX males with no evidence of off-pathway involvement. Likewise, rapid-on/off ramping stimuli also indicated that the functional deficit was localized to the on pathway. Analysis of non-human primate retinal responses after drug application demonstrated a complexity to on/off-pathway contributions to ramping on/off ERG responses not previously anticipated. These results support the hypothesis that nyctalopin acts principally or exclusively within the on pathway at the level of depolarizing bipolar cells, and thus human CSNB1- NYX subjects provide an opportunity to probe the primate visual system for consequences of on-pathway deficits.

Reciprocal inhibition of voltage-gated potassium currents (IK(V)) by activation of cannabinoid CB1and dopamine D1receptors in ON bipolar cells of goldfish retina

2005 ◽  
Vol 22 (1) ◽  
pp. 55-63 ◽  
Author(s):  
SHIH-FANG FAN ◽  
STEPHEN YAZULLA
Keyword(s):  
G Protein ◽  
Receptor Agonist ◽  
Lucifer Yellow ◽  
Reciprocal Inhibition ◽  
Receptor Activation ◽  
Light Signal ◽  
Bipolar Cells ◽  
Protein G ◽  
Calcium Dependent ◽  
Voltage Dependent

Cannabinoid CB1receptor (viaGs) and dopamine D2receptor (viaGi/o) antagonistically modulate goldfish cone membrane currents. As ON bipolar cells have CB1and D1receptors, but not D2receptors, we focused on whether CB1receptor agonist and dopamine interact to modulate voltage-dependent outward membrane K+currentsIK(V)of the ON mixed rod/cone (Mb) bipolar cells. Whole-cell currents were recorded from Mb bipolar cells in goldfish retinal slices. Mb bipolar cells were identified by intracellular filling with Lucifer yellow. The bath solution was calcium-free and contained 1 mM cobalt to block indirect calcium-dependent effects. Dopamine (10 μM) consistently increasedIK(V)by a factor of 1.57 ± 0.12 (S.E.M.,n= 15). A CB receptor agonist, WIN 55212-2 (0.25–1 μM), had no effect, but 4 μM WIN 55212-2 suppressedIK(V)by 60%. IfIK(V)was first increased by 10 μM dopamine, application of WIN 55212-2 (0.25–1 μM) reversibly blocked the effect of dopamine even though these concentrations of WIN 55212-2 had no effect of their own. If WIN 55212-2 was applied first and dopamine (10 μM) was added to the WIN-containing solution, 0.1 μM WIN 55212-2 blocked the effect of dopamine. All effects of WIN 55212-2 were blocked by coapplication of SR 141716A (CB1antagonist) and pretreatment with pertussis toxin (blocker of Gi/o) indicating actionviaCB1receptor activation of G protein Gi/o. Coactivation of CB1and D1receptors on Mb bipolar cells produces reciprocal effects onIK(V). The CB1-evoked suppression ofIK(V)is mediated by G protein Gi/o, whereas the D1-evoked enhancement is mediated by G protein Gs. As dopamine is a retinal “light” signal, these data support our notion that endocannabinoids function as a “dark” signal, interacting with dopamine to set retinal sensitivity.

Properties of synaptic transmission from photoreceptors to bipolar cells in the mudpuppy retina

1993 ◽  
Vol 69 (2) ◽  
pp. 352-360 ◽  
Author(s):  
H. G. Kim ◽  
R. F. Miller
Keyword(s):  
Kynurenic Acid ◽  
Response Times ◽  
Plexiform Layer ◽  
Bipolar Cells ◽  
Slice Preparation ◽  
Peak Response ◽  
Rods And Cones ◽  
Significant Difference ◽  
Pharmacological Studies ◽  
Whole Cell Recordings

1. Simultaneous, whole-cell recordings were obtained from synaptically coupled photoreceptor/bipolar cell pairs, by the use of direct visualization in a superfused, mudpuppy retinal slice preparation. 2. OFF-bipolar cells (BPs) generated sign-conserving responses when extrinsic current was injected into rods and cones, whereas ON-BPs generated a sign-reversing response. OFF-BPs (n = 24) responded faster than ON-BPs (n = 12), in terms of response latency (27.8 vs. 80.6 ms) and peak response times (50.5 vs. 159.8 ms) when current was injected into photoreceptors. We did not detect any significant difference between rod- versus cone-mediated latency or peak response times in the ON- and OFF-BP subtypes. 3. Rod and cone inputs to OFF-BPs were blocked by kynurenic acid (Kyn), but the doses required were significantly higher for rod inputs: the IC50 (the concentration at which an antagonist blocks 50% of the responses) for Kyn was 0.3 mM for cone inputs and 1 mM for rod inputs. 4. Rod inputs to OFF-BPs showed the same Kyn sensitivity as rod inputs to horizontal cells (HCs). However, cone inputs to HCs (IC50 < 200 microM) were more sensitive to Kyn than those to OFF-BPs. 5. The pharmacological studies presented here, together with previous studies, suggest that the sign-conserving pathway in the outer plexiform layer of the mudpuppy retina involves at least three subtypes of glutamate receptors: 1) cone-activated receptors of HCs; 2) cone-activated receptors of OFF-BPs; and 3) rod-activated receptors found in HCs and BPs.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Dopamine D1 receptor activation contributes to light-adapted changes in retinal inhibition to rod bipolar cells

2018 ◽  
Vol 120 (2) ◽  
pp. 867-879 ◽  
Author(s):  
Michael D. Flood ◽  
Johnnie M. Moore-Dotson ◽  
Erika D. Eggers
Keyword(s):  
Light Adaptation ◽  
Amacrine Cell ◽  
Amacrine Cells ◽  
Receptor Activation ◽  
Bipolar Cells ◽  
D1 Receptor ◽  
D1 Receptors ◽  
Light Responses ◽  
Dopamine Modulation ◽  
Rod Bipolar Cells

Dopamine modulation of retinal signaling has been shown to be an important part of retinal adaptation to increased background light levels, but the role of dopamine modulation of retinal inhibition is not clear. We previously showed that light adaptation causes a large reduction in inhibition to rod bipolar cells, potentially to match the decrease in excitation after rod saturation. In this study, we determined how dopamine D1 receptors in the inner retina contribute to this modulation. We found that D1 receptor activation significantly decreased the magnitude of inhibitory light responses from rod bipolar cells, whereas D1 receptor blockade during light adaptation partially prevented this decline. To determine what mechanisms were involved in the modulation of inhibitory light responses, we measured the effect of D1 receptor activation on spontaneous currents and currents evoked from electrically stimulating amacrine cell inputs to rod bipolar cells. D1 receptor activation decreased the frequency of spontaneous inhibition with no change in event amplitudes, suggesting a presynaptic change in amacrine cell activity in agreement with previous reports that rod bipolar cells lack D1 receptors. Additionally, we found that D1 receptor activation reduced the amplitude of electrically evoked responses, showing that D1 receptors can modulate amacrine cells directly. Our results suggest that D1 receptor activation can replicate a large portion but not all of the effects of light adaptation, likely by modulating release from amacrine cells onto rod bipolar cells. NEW & NOTEWORTHY We demonstrated a new aspect of dopaminergic signaling that is involved in mediating light adaptation of retinal inhibition. This D1 receptor-dependent mechanism likely acts through receptors located directly on amacrine cells, in addition to its potential role in modulating the strength of serial inhibition between amacrine cells. Our results also suggest that another D2/D4 receptor-dependent or dopamine-independent mechanism must also be involved in light adaptation of inhibition to rod bipolar cells.

Hereditary Retinal Disease-Related Retinal Detachment; Risk Factors, Pathogenesis, Clinic, and Management

2020 ◽  
pp. 193-200
Keyword(s):  
Risk Factors ◽  
Retinal Detachment ◽  
Cardiovascular System ◽  
Proliferative Vitreoretinopathy ◽  
Delayed Diagnosis ◽  
Retinal Disease ◽  
Skeletal System ◽  
Younger Age ◽  
Hereditary Retinal Disease

Hereditary retinal disease (HRD) is a group of pathologies characterized by histologically abnormally developing vitreous gel associated with peripheral retinal degenerative or proliferative changes. In HRD alterations in the structure of the vitreous with abnormal vitreoretinal adhesions can predispose to developing Retinal Detachment (RD). Many HRD is seen with a part of syndromes most of which have systemic abnormalities affecting the joints, skeletal system, and cardiovascular system.  Due to delayed diagnosis in younger age patients,  without prominent symptoms, most patients with HR presented with proliferative vitreoretinopathy PVR and macula-involving RD.

Ionic Mechanisms of Muscarinic Depolarization in Entorhinal Cortex Layer II Neurons

1997 ◽  
Vol 77 (4) ◽  
pp. 1829-1843 ◽  
Author(s):  
Ruby Klink ◽  
Angel Alonso
Keyword(s):  
Entorhinal Cortex ◽  
Cell Activity ◽  
Input Resistance ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Tissue Slices ◽  
Voltage Range ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Ionic Mechanisms

Klink, Ruby and Angel Alonso. Ionic mechanisms of muscarinic depolarization in entorhinal cortex layer II neurons. J. Neurophysiol. 77: 1829–1843, 1997. The mechanisms underlying direct muscarinic depolarizing responses in the stellate cells (SCs) and non-SCs of medial entorhinal cortex layer II were investigated in tissue slices by intracellular recording and pressure-pulse applications of carbachol (CCh). Subthreshold CCh depolarizations were largely potentiated in amplitude and duration when paired with a short DC depolarization that triggered cell firing. During Na+ conductance block, CCh depolarizations were also potentiated by a brief DC depolarization that allowed Ca2+ influx and the potentiation was more robust in non-SCs than in SCs. Also, in non-SCs, CCh depolarizations could be accompanied by spikelike voltage oscillations at a slow frequency. In both SCs and non-SCs, the voltage-current ( V-I) relations were similarly affected by CCh, which caused a shift to the left of the steady-state V-I relations over the entire voltage range and an increase in apparent slope input resistance at potentials positive to about −70 mV. CCh responses potentiated by Ca2+ influx demonstrated a selective increase in slope input resistance at potentials positive to about −75 mV in relation to the nonpotentiated responses. K+ conductance block with intracellular injection of Cs+ (3 M) and extracellular Ba2+ (1 mM) neither abolished CCh depolarizations nor resulted in any qualitatively distinct effect of CCh on the V-I relations. CCh depolarizations were also undiminished by block of the time-dependent inward rectifier I h with extracellular Cs+. However, CCh depolarizations were abolished during Ca2+ conductance block with low-Ca2+ (0.5 mM) solutions containing Cd2+, Co2+, or Mn2+, as well asby intracellular Ca2+ chelation with bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid. Inhibition of the Na+-K+ ATPase with strophanthidin resulted in larger CCh depolarizations. On the other hand, when NaCl was replaced by N-methyl-d-glucamine, CCh depolarizations were largely diminished. CCh responses were blocked by 0.8 μM pirenzepine, whereas hexahydro-sila-difenidolhydrochloride,p-fluoroanalog (p-F-HHSiD) and himbacine were only effective antagonists at 5- to 10-fold larger concentrations. Our data are consistent with CCh depolarizations being mediated in both SCs and non-SCs by m1 receptor activation of a Ca2+-dependent cationic conductance largely permeable to Na+. Activation of this conductance is potentiated in a voltage-dependent manner by activity triggering Ca2+ influx. This property implements a Hebbian-like mechanism whereby muscarinic receptor activation may only be translated into substantial membrane depolarization if coupled to postsynaptic cell activity. Such a mechanism could be highly significant in light of the role of the entorhinal cortex in learning and memory as well as in pathologies such as temporal lobe epilepsy.

A role for 5HT3 receptors in visual processing in the mammalian retina

1993 ◽  
Vol 10 (3) ◽  
pp. 511-522 ◽  
Author(s):  
William J. Brunken ◽  
Xiao-Tao Jin
Keyword(s):  
Visual Processing ◽  
Ganglion Cells ◽  
Cell Activity ◽  
Phosphatidyl Inositol ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Reciprocal Effect ◽  
Mammalian Retina ◽  
Messenger System

AbstractWe investigated the role of 5HT3 receptors in the mammalian retina using electrophysiological techniques to monitor ganglion cell activity. Activation of 5HT3 receptors with the selective agonist 1-phenylbiguanide (PBG) increased the ON responses of ON-center ganglion cells, while decreasing the OFF responses of OFF-center cells. The application of a selective 5HT3 antagonist had a reciprocal effect, namely it reduced the center response in ON-center cells and concomitantly increased the center responses in OFF-center cells. Since putative serotoninergic amacrine cells in the retina are connected specifically to the rod bipolar cell, these agents most likely affect the rod bipolar terminal. These data, together with previous studies, suggest that both 5HT2 and 5HT3 receptors mediate an excitatory influence which serves to facilitate the output from rod bipolar cells, the former via a phosphatidyl inositol second-messenger system, and the latter via a direction channel.

Activation of adenosine A2A receptors alters postsynaptic currents and depolarizes neurons of the supraoptic nucleus

2006 ◽  
Vol 291 (2) ◽  
pp. R359-R366 ◽  
Author(s):  
Todd A. Ponzio ◽  
Yu-Feng Wang ◽  
Glenn I. Hatton
Keyword(s):  
Supraoptic Nucleus ◽  
Cell Activity ◽  
Brain Slices ◽  
Cell Types ◽  
Receptor Activation ◽  
A2a Receptors ◽  
Postsynaptic Currents ◽  
Cgs 21680 ◽  
Whole Cell Patch Clamp ◽  
Sites Of Action

Supraoptic nucleus (SON) neurons secrete oxytocin or vasopressin in response to various physiological stimuli (e.g., lactation/suckling, dehydration). Released near fenestrated capillaries of the neurohypophysis, these peptides enter the blood and travel to peripheral target organs. The pervasive neuromodulator adenosine, acting at A1 receptors, is an important inhibitory regulator of magnocellular neuroendocrine cell activity. Another high-affinity adenosine receptor exists in this system, however. We examined the physiological effects of adenosine A2A receptor activation and determined its localization among various cell types within the SON. In whole cell patch-clamp recordings from rat brain slices, application of the selective adenosine A2A receptor agonist CGS-21680 caused membrane depolarizations in SON neurons, often leading to increased firing activity. Membrane potential changes were persistent (>10 min) and could be blocked by the selective A2A receptor antagonist ZM-241385, or GDP-β-S, the latter suggesting postsynaptic sites of action. However, ±-α-methyl-(4-carboxyphenyl)glycine or TTX also blocked CGS-21680 effects, indicating secondary actions on postsynaptic neurons. In voltage-clamp mode, application of CGS-21680 caused a slight increase (∼8%) in high-frequency clusters of excitatory postsynaptic currents. With the use of specific antibodies, adenosine A2A receptors were immunocytochemically localized to both the magnocellular neurons and astrocytes of the SON. Ecto-5′nucleotidase, an enzyme involved in the metabolism of ATP to adenosine, was also localized to astrocytes of the SON. These results demonstrate that adenosine acting at A2A receptors can enhance the excitability of SON neurons and modulate transmitter release from glutamatergic afferents projecting to the nucleus. We suggest that adenosine A2A receptors may function in neuroendocrine regulation through both direct neuronal mechanisms and via actions involving glia.

Membrane currents evoked by excitatory amino acid agonists in ON bipolar cells of the mudpuppy retina

1993 ◽  
Vol 70 (4) ◽  
pp. 1326-1338 ◽  
Author(s):  
W. B. Thoreson ◽  
R. F. Miller
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Outward Current ◽  
Receptor Activation ◽  
Extracellular Calcium ◽  
Bipolar Cells ◽  
Membrane Currents ◽  
Cation Channels ◽  
Gaba Uptake ◽  
Conductance Increase

1. Whole-cell patch-clamp recordings were obtained from ON bipolar cells in a retinal slice preparation of the mudpuppy, Necturus maculosus. The effects of excitatory amino acid (EAA) agonists applied in the presence of cobalt (2-5 mM) were examined. 2. At the holding potential of -50 mV, L-2-amino-4-phosphonobutanoic acid (L-AP4, 5-10 microM) evoked an outward current accompanied by a conductance decrease. The zero current potential of the L-AP4-evoked current was near 0 mV independent of whether the intracellular Ringer solution contained CsCl or CsCH3SO4. The currents evoked by light were also accompanied by a conductance decrease and reversed near 0 mV. Replacing external sodium with choline or N-methyl-D-glucamine generated an outward current and suppressed the response to L-AP4. The response to L-AP4 was enhanced by removing extracellular calcium and suppressed by increasing extracellular calcium. These results indicate that L-AP4 closes nonspecific cation channels that are blocked by extracellular calcium. 3. In 2 mM cobalt, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 50-100 microM) evoked membrane currents that were accompanied by a conductance increase. AMPA-evoked currents exhibited a significant chloride dependence and were suppressed by gamma-aminobutyric acid-A (GABAA) antagonists bicuculline and picrotoxin; a GABA uptake blocker, nipecotic acid; and a glycine antagonist, strychnine. AMPA-induced currents were virtually absent in the presence of 5 mM cobalt and nominally 0 mM extracellular calcium. These results indicate that the conductance increase induced by AMPA in the presence of 2 mM cobalt is largely the result of calcium-dependent synaptic inputs onto GABAA and glycine receptors of ON bipolar cells. 4. N-methyl-D-aspartic acid (250 microM) was ineffective when applied in the presence of 100 microM cadmium or 2 mM cobalt. 5. 1S,3R/1R,3S-1-aminocyclopentane-1,3-dicarboxylic acid (100-200 microM) evoked an outward current accompanied by a conductance decrease and appears to be an agonist at the L-AP4 receptor. 6. The findings of this study suggest that the only type of EAA receptor in mudpuppy ON bipolar cells is the L-AP4 receptor and that L-AP4 receptor activation results in the closing of nonspecific cation channels that are blocked by extracellular calcium.

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