Contributions of GABAA receptors and GABAC receptors to acetylcholine release and directional selectivity in the rabbit retina

1997 ◽  
Vol 14 (5) ◽  
pp. 939-948 ◽  
Author(s):  
Stephen C. Massey ◽  
David M. Linn ◽  
Christopher A. Kittila ◽  
Wajid Mirza
Keyword(s):  
Ganglion Cells ◽  
Bipolar Cells ◽  
High Dose ◽  
Directional Selectivity ◽  
Ach Release ◽  
Gaba Antagonists ◽  
Inhibitory Neurotransmitter ◽  
Postsynaptic Receptors ◽  
Release Of Acetylcholine ◽  
Sr 95531

AbstractGABA is a major inhibitory neurotransmitter in the mammalian retina and it acts at many different sites via a variety of postsynaptic receptors. These include GABAA receptors and bicuculline-resistant GABAC receptors. The release of acetylcholine (ACh) is inhibited by GABA and strongly potentiated by GABA antagonists. In addition, GABA appears to mediate the null inhibition which is responsible for the mechanism of directional selectivity in certain ganglion cells. We have used these two well-known examples of GABA inhibition to compare three GABA antagonists and assess the contributions of GABAA and GABAC receptors. All three GABA antagonists stimulated ACh release by as much as ten-fold. By this measure, the ED50s for SR-95531, bicuculline, and picrotoxin were 0.8, 7.0, and 14 μM, respectively. Muscimol, a potent GABAA agonist, blocked the effects of SR-95531 and bicuculline, but not picrotoxin. This indicates that SR-95531 and bicuculline are competitive antagonists at the GABAA receptor, while picrotoxin blocks GABAA responses by acting at a different, nonreceptor site such as the chloride channel. In the presence of a saturating dose of SR-95531 to completely block GABAA receptors, picrotoxin caused a further increase in the release of ACh. This indicates that picrotoxin potentiates ACh release by a mechanism in addition to the block of GABAA responses, possibly by also blocking GABAC receptors, which have been associated with bipolar cells. All three GABA antagonists abolished directionally selective responses from ON/OFF directional-selective (DS) ganglion cells. In this system, the ED50s for SR-95531, bicuculline, and picrotoxin were 0.7 μM, 8 μM, and 94.6 μM, respectively. The results with SR-95531 and bicuculline indicate that GABAA receptors mediate the inhibition responsible for directional selectivity. The addition of picrotoxin to a high dose of SR-95531 caused no further increase in firing rate. The comparatively high dose required for picrotoxin also suggests that GABAC receptors do not contribute to directional selectivity. This in turn suggests that feedforward GABAA inhibition, as opposed to feedback at bipolar terminals, is responsible for the null inhibition underlying directional selectivity.

GABA inhibits ACh release from the rabbit retina: A direct effect or feedback to bipolar cells?

1992 ◽  
Vol 8 (2) ◽  
pp. 97-106 ◽  
Author(s):  
David M. Linn ◽  
Stephen C. Massey
Keyword(s):  
Direct Effect ◽  
Negative Feedback ◽  
Bipolar Cell ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Rabbit Retina ◽  
Ach Release ◽  
Gaba Antagonists ◽  
Direct Input ◽  
Cholinergic Amacrine Cells

AbstractThe cholinergic amacrine cells of the rabbit retina may be labeled with [3H]-Ch and the activity of the cholinergic population monitored by following the release of [3H]-ACh. We have tested the effect of muscimol, a potent GABAA agonist, on (1) the light-evoked release of ACh, presumably mediated via bipolar cells, which are known to have a direct input to the cholinergic amacrine cells and (2) ACh release produced by exogenous glutamate analogs that probably have a direct effect on cholinergic amacrine cells. Muscimol blocked the light-evoked release of ACh with an IC50 of 1.0 μM. In contrast, ACh release produced by nonsaturating doses of kainate or NMDA was not reduced even by 100 μM muscimol. Thus, we have been unable to demonstrate a direct effect of GABA on the cholinergic amacrine cells.GABA antagonists, such as picrotoxin, caused a large increase in the base release and potentiated the light-evoked release of ACh. Both these effects were abolished by DNQX, a kainate antagonist that blocks the input to cholinergic amacine cells from bipolar cells. DNQX blocked the effects of picrotoxin even when controls showed that the mechanism of ACh release was still functional. Together, these results imply that the dominant site for the GABA-mediated inhibition of ACh release is on the bipolar cell input to the cholinergic amacrine cells. This is consistent with previous anatomical and physiological evidence that bipolar cells receive negative feedback from GABA amacrine cells.

The role of NMDA channels in rabbit retinal directional selectivity

2000 ◽  
Vol 17 (2) ◽  
pp. 291-302 ◽  
Author(s):  
DARREL S. TJEPKES ◽  
FRANKLIN R. AMTHOR
Keyword(s):  
Ganglion Cells ◽  
Amacrine Cells ◽  
Directional Selectivity ◽  
Free Medium ◽  
Null Direction ◽  
Preferred Direction ◽  
Dendritic Membrane ◽  
Release Of Acetylcholine ◽  
Nmda Channels ◽  
Free Media

It has been previously demonstrated that the majority of the glutamatergic input to directionally selective (DS) ganglion cells in the rabbit retina is mediated by NMDA receptors. To examine whether NMDA channels have any role in directional selectivity, we eliminated magnesium from the superfusion medium to prevent the magnesium block of the channels at hyperpolarized membrane potentials. During superfusion in magnesium-free media, the response to null-direction motion increased to the level of the response to preferred-direction motion. This effect was specifically mediated by NMDA channels because subsequent blocking of the NMDA channels with AP7 restored directional selectivity. We also tested whether the increase in the null-direction response in magnesium-free medium was due to an increased release of acetylcholine from the cholinergic amacrine cells, rather than an effect on the DS ganglion cells themselves, by blocking acetylcholine transmission with d-tubocurarine during superfusion with the magnesium-free medium. During zero-magnesium superfusion, d-tubocurarine reduced both the preferred- and null-direction responses of DS ganglion cells but did not restore directional selectivity. These findings suggest that null-direction motion normally causes portions of the dendritic membrane of the directionally selective ganglion cell to be maintained at a sufficiently negative potential that the NMDA channels are blocked by magnesium ions. This result is discussed in terms of several models for the mechanisms of directional selectivity.

Is the input to a GABAergic synapse the sole asymmetry in turtle's retinal directional selectivity?

1996 ◽  
Vol 13 (3) ◽  
pp. 423-439 ◽  
Author(s):  
Randall D. Smith ◽  
Norberto M. Grzywacz ◽  
Lyle J. Borg-Graham
Keyword(s):  
Ganglion Cells ◽  
Visual Stimuli ◽  
Directional Selectivity ◽  
Null Direction ◽  
Gabaergic Synapse ◽  
Inhibitory Neurotransmitter ◽  
Alternative Models ◽  
Inhibition Model ◽  
Preferred Direction

AbstractWe examined the effects of picrotoxin and pentylenetetrazol (PTZ) on the responses to motions of ON-OFF directionally selective (DS) ganglion cells of the turtle's retina. These drugs are antagonists of the inhibitory neurotransmitter GABA. For continuous motions, picrotoxin markedly reduced the overall directionality of the cells. In 21% of the cells, directional selectivity was lost regardless of speed and contrast. However, other cells maintained their preferred direction despite saturating concentrations of picrotoxin. And in most cells, loss, maintenance, or even reversal of preferred and null directions could occur as speed and contrast were modulated. In 50% of the cells, reversal of preferred and null directions occurred at some condition of visual stimuli. However, picrotoxin did not tend to alter the preferred-null axis for directional selectivity. For apparent motions, picrotoxin made motion facilitation, which normally occurs exclusively in preferred-direction responses, to become erratic and often occur during null-direction motions. Finally, PTZ had effects similar to picrotoxin but with less potency. The results in this paper indicated that models of directional selectivity based solely on a GABAergic implementation of Barlow and Levick's asymmetric-inhibition model do not apply to the turtle retina. Alternative models may comprise multiple directional mechanisms and/or a symmetric inhibitory one, but not asymmetric facilitation.

scholarly journals Neuronal release of endogenous dopamine from corpus of guinea pig stomach

1997 ◽  
Vol 273 (5) ◽  
pp. G1044-G1050
Author(s):  
Kazuko Shichijo ◽  
Yasuko Sakurai-Yamashita ◽  
Ichiro Sekine ◽  
Kohtaro Taniyama
Keyword(s):  
Guinea Pig ◽  
Ganglion Cells ◽  
Splanchnic Nerve ◽  
Muscle Layer ◽  
Nerve Fibers ◽  
Endogenous Dopamine ◽  
Dopamine Content ◽  
Release Of Acetylcholine ◽  
Gastric Corpus ◽  
Guinea Pig Stomach

Neuronal release of endogenous dopamine was identified in mucosa-free preparations (muscle layer including intramural plexus) from guinea pig stomach corpus by measuring tissue dopamine content and dopamine release and by immunohistochemical methods using a dopamine antiserum. Dopamine content in mucosa-free preparations of guinea pig gastric corpus was one-tenth of norepinephrine content. Electrical transmural stimulation of mucosa-free preparations of gastric corpus increased the release of endogenous dopamine in a frequency-dependent (3–20 Hz) manner. The stimulated release of dopamine was prevented by either removal of external Ca2+ or treatment with tetrodotoxin. Dopamine-immunopositive nerve fibers surrounding choline acetyltransferase-immunopositive ganglion cells were seen in the myenteric plexus of whole mount preparations of gastric corpus even after bilateral transection of the splanchnic nerve proximal to the junction with the vagal nerve (section of nerves between the celiac ganglion and stomach). Domperidone and sulpiride potentiated the stimulated release of acetylcholine and reversed the dopamine-induced inhibition of acetylcholine release from mucosa-free preparations. These results indicate that dopamine is physiologically released from neurons and from possible dopaminergic nerve terminals and regulates cholinergic neuronal activity in the corpus of guinea pig stomach.

The Retina of Asian and African Elephants: Comparison of Newborn and Adult

2017 ◽  
Vol 89 (2) ◽  
pp. 84-103 ◽  
Author(s):  
Heidrun Kuhrt ◽  
Andreas Bringmann ◽  
Wolfgang Härtig ◽  
Gudrun Wibbelt ◽  
Leo Peichl ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Ganglion Cell ◽  
Glial Cells ◽  
Ganglion Cells ◽  
Bipolar Cells ◽  
Horizontal Cells ◽  
Retinal Ganglion ◽  
Terrestrial Mammals ◽  
Contrast Perception ◽  
First Time

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.

Vasoactive intestinal polypeptide modulates GABAA receptor function in bipolar cells and ganglion cells of the rat retina

1992 ◽  
Vol 67 (4) ◽  
pp. 791-797 ◽  
Author(s):  
M. L. Veruki ◽  
H. H. Yeh
Keyword(s):  
Gabaa Receptor ◽  
Vasoactive Intestinal Polypeptide ◽  
Ganglion Cells ◽  
Bipolar Cells ◽  
Current Response ◽  
Gamma Aminobutyric Acid ◽  
Patch Clamp Recording ◽  
Rat Retina ◽  
Neuronal Populations ◽  
Intestinal Polypeptide

1. The effect of vasoactive intestinal polypeptide (VIP) on bipolar cells and ganglion cells freshly dissociated from the rat retina was studied under voltage clamp with the use of patch-clamp recording in the whole-cell configuration. 2. Application of VIP (1-100 microM) by itself resulted in no detectable current response in either bipolar cells or ganglion cells. However, gamma-aminobutyric acid (GABA)-activated macroscopic current responses elicited in both neuronal populations were potentiated on superimposed exposure to the neuropeptide. 3. GABA-activated chloride currents and muscimol-induced current responses were similarly potentiated on exposure to VIP, suggesting a synergistic interaction between VIP and GABAA receptor mechanisms. 4. We postulate that VIP plays a neuromodulatory role by regulating the excitability of inner retinal neurons and in this way modulates the efficacy of synaptic transmission in the retina.

scholarly journals Transplanted pluripotent stem cell-derived photoreceptor precursors elicit conventional and unusual light responses in mice with advanced retinal degeneration

2020 ◽  
Author(s):  
Darin Zerti ◽  
Gerrit Hilgen ◽  
Birthe Dorgau ◽  
Joseph Collin ◽  
Marius Ader ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Ganglion Cells ◽  
Light Sensitivity ◽  
Bipolar Cells ◽  
Therapeutic Interventions ◽  
Light Responses ◽  
Motion Sensitivity ◽  
Retinal Dystrophies ◽  
End Stage

SummaryRetinal dystrophies often lead to blindness. Developing therapeutic interventions to restore vision is therefore of paramount importance. Here we demonstrate the ability of pluripotent stem cell-derived cone precursors to engraft and restore light responses in the Pde6brd1 mouse, an end-stage photoreceptor degeneration model. Up to 1.5% of precursors integrated into the host retina, differentiated into cones and formed synapses with bipolar cells. Half of the transplanted mice exhibited visual behaviour and 33% showed binocular light sensitivity. The majority of ganglion cells exhibited contrast-sensitive ON, OFF or ON-OFF light responses and even motion sensitivity. Many cells also exhibited unusual responses (e.g. light-induced suppression), presumably reflecting remodelling of the neural retina. Our data indicate that despite relatively low engraftment yield, engrafted pluripotent stem cell-derived cone precursors can elicit light responsiveness even at advanced degeneration stages. Further work is needed to improve engraftment yield and counteract retinal remodelling to achieve useful clinical applications.

Degeneration and Regrowth of Adrenergic Nerve Fibers in the Rat Peripheral Tissues after 6-Hydroxydopamine

1971 ◽  
Vol 49 (4) ◽  
pp. 345-355 ◽  
Author(s):  
J. de Champlain
Keyword(s):  
Ganglion Cells ◽  
Adrenergic Innervation ◽  
Nerve Fibers ◽  
Adrenergic Nerve ◽  
High Dose ◽  
Rat Tissues ◽  
Peripheral Tissues ◽  
Endogenous Noradrenaline ◽  
6 Hydroxydopamine ◽  
Noradrenaline Levels

Histofluorescent and biochemical changes in the adrenergic nervous system were followed up in rat tissues after one single intravenous injection of a high dose of 100 mg/kg of 6-hydroxydopamine (6-OH-DA). This treatment results in the rapid disappearance of terminal and preterminal fibers in the iris, atria, and small arteries of rats, whereas endogenous noradrenaline pools of the heart are 95% depleted. The capacity of the adrenergic nerve to take up and accumulate tritiated noradrenaline is reduced proportionally to the reduction in endogenous noradrenaline levels. These changes are compatible with the concept of a complete sympathectomy induced by the specific toxic action of 6-OH-DA on the adrenergic fibers. This sympathectomy is not permanent, however, and numerous bundles of preterminal fibers start to grow in the iris and atria within 4 to 5 days following injection. Progressively, in the following weeks, these fibers distribute over the whole organ and give birth to terminal fibers which form a new adrenergic plexus in these tissues. A completely normal innervation is restored 2 to 3 months after administration of 6-OH-DA. The endogenous noradrenaline levels rise progressively in parallel to the development of the new plexus of fibers. Since a complete regeneration of the adrenergic innervation can be demonstrated in the weeks following injection of 6-OH-DA, it appears that this compound can selectively destroy the adrenergic terminal and preterminal fibers without causing a degeneration of the adrenergic ganglion cells.

Some Observations on the Physiology and Pharmacology of the Nerve Endings in the Crop and Gizzard of the Earthworm, with Special Reference to the Effects of Cooling

1945 ◽  
Vol 21 (1-2) ◽  
pp. 46-57
Author(s):  
N. AMBACHE ◽  
A. ST J. DIXON ◽  
E. A. WRIGHT
Keyword(s):  
Ganglion Cells ◽  
Rhythmic Activity ◽  
Inhibitory Effect ◽  
Nerve Endings ◽  
Rhythmic Movements ◽  
Cholinergic Nerve ◽  
Enteric Plexus ◽  
Small Doses ◽  
Release Of Acetylcholine ◽  
Parasympathetic Ganglion

1. The effect of cooling on the properties of the crop and gizzard of the earthworm has been investigated. Evidence is advanced that the rhythmic movements of the ‘warm’ preparation are neurogenic in origin and peristaltic in nature. They are abolished by nicotine and by cooling, but not by atropine. 2. Acetylcholine contracts the muscle in the crop and gizzard. This effect is abolished by atropine. The excitability of the muscle to acetylcholine is not lost after cooling. 3. Peristalsis is accompanied in the ‘warm’ preparation by a continual liberation of acetylcholine. This is absent in cold preparations. The disappearance of rhythmic activity in these is associated with the loss of acetylcholine synthesis. 4. In the ‘warm’ crop and gizzard, potassium produces contraction which is enhanced by eserine, but not abolished by nicotine or by atropine. With higher doses of potassium, stimulation is followed by inhibition. After short periods of cooling, the motor response to potassium is lost, but the inhibitory effect is still present. Prolonged cooling abolishes both actions. It is suggested that the augmentor action of potassium is due to an intermediate release of acetylcholine from the cholinergic nerve endings, and the inhibitory action to a liberation of adrenaline from the adrenergic nerves in the crop and gizzard. 5. Calcium inhibits the rhythmic activity of ‘warm’ preparations, and the effect of potassium. It has no action on cooled preparations, and in these it does not affect the contractions produced by acetylcholine. It is suggested that calcium acts on ‘warm’ preparations by preventing the release of acetylcholine from cholinergic nerve endings. 6. The action of adrenaline on ‘warm’ preparations is twofold: small doses have an augmentor effect; larger doses are inhibitory. After cooling, adrenaline has no action by itself. It is suggested that the augmentor effect of adrenaline is due to an improvement in acetylcholine-transmission at the cholinergic nerve endings. 7. Small doses of barium contract the ‘warm’ preparation. This action is inhibited by calcium, abolished by nicotine, and is lost after cooling. It is suggested that the action of such doses of barium is due to a stimulation of parasympathetic ganglion cells. 8. The presence of multipolar nerve cells in the enteric plexus was demonstrated in histological sections of the crop and gizzard. These were found lying between the circular and longitudinal muscle layers, in a position analogous to that of Auerbach's plexus.

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