Rabbit retinal ganglion cell responses to nicotine can be mediated by β2-containing nicotinic acetylcholine receptors

2003 ◽  
Vol 20 (6) ◽  
pp. 651-662 ◽  
Author(s):  
CHRISTIANNE E. STRANG ◽  
FRANKLIN R. AMTHOR ◽  
KENT T. KEYSER

Acetylcholine (ACh) affects the response properties of many retinal ganglion cells (GCs) through the activation of nicotinic acetylcholine receptors (nAChRs). To date there have been few studies directly correlating the expression of specific nAChR subtypes with the physiological and morphological characteristics of specific retinal GCs. This study was designed to correlate responses to nicotine application with immunohistochemical evidence of nAChR expression in physiologically and morphologically identified ganglion cells. Extracellular recordings were used to physiologically identify rabbit retinal GCs, based on responses to light stimulation. Cells were then tested for responses to nicotine application and/or for expression of nAChRs, as judged by immunoreactivity to mAb210, an nAChR antibody. The morphologies of many physiologically identified cells were also determined by dye injection. More than three-fourths of ganglion cells tested responded to nicotine application under cobalt-induced synaptic blockade. The nicotine sensitivity was consistent with nAChR immunoreactivity and was also correlated with specific morphological subgroups of GCs. Overall, approximately two-thirds of all physiologically identified GCs that were processed for immunohistochemistry displayed immunoreactivity. In total, 18 of 22 physiologically identified cells demonstrated both sensitivity to nicotine application under synaptic blockade and mAb210 immunoreactivity (mAb210-IR). Thus, mAb210-IR is likely to represent functional nAChRs that can modulate retinal information processing and visual functioning via direct excitation of a number of GC classes.

2002 ◽  
Vol 19 (4) ◽  
pp. 427-438 ◽  
Author(s):  
B.T. REED ◽  
F.R. AMTHOR ◽  
K.T. KEYSER

The responses of many ganglion cells in the rabbit retina are mediated, at least in part, by acetylcholine (ACh) acting on neuronal nicotinic acetylcholine receptors (nAChRs). nAChRs are comprised of α and β subunits; three β subunits and nine α subunits of nAChRs have been identified and these subunits can combine to form a large number of functionally distinct nAChR subtypes. We examined the effects of cholinergic agents on the light-evoked responses of ganglion cells to determine which nAChR subtypes mediate the effects of ACh. Extracellular recordings of retinal ganglion cells were made in intact everted eyecup preparations and nicotinic agonists and antagonists were added to the superfusate. While several ganglion cell classes exhibited methyllycaconitine (MLA) sensitivity, the directionally selective (DS) ganglion cells were most sensitive; exposure to 30 nanomolar MLA, a concentration reportedly too low to affect αBgt-insensitive nAChRs, suppressed the stimulus-evoked responses of DS cells without eliminating directional selectivity. Epibatidine, which at low concentrations is an agonist selective for αBgt-insensitive nAChRs, stimulated firing of various cell types including DS ganglion cells at low nanomolar concentrations. The effects of the various agents tested persisted under cobalt-induced synaptic blockade. The low nanomolar MLA and epibatidine sensitivity of DS cells suggests that DS ganglion cells express both αBgt-sensitive and αBgt-insensitive nAChRs. Other ganglion cell types appear to express only αBgt-sensitive nAChRs but not αBgt-insensitive nAChRs.


2010 ◽  
Vol 28 (1) ◽  
pp. 51-60 ◽  
Author(s):  
CHRISTIAN PULLER ◽  
SILKE HAVERKAMP

AbstractColor vision in mammals is based on the expression of at least two cone opsins that are sensitive to different wavelengths of light. Furthermore, retinal pathways conveying color-opponent signals are required for color discrimination. Most of the primates are trichromats, and “color-coded channels” of their retinas are unveiled to a large extent. In contrast, knowledge of cone-selective pathways in nonprimate dichromats is only slowly emerging, although retinas of dichromats like mice or rats are extensively studied as model systems for retinal information processing. Here, we review recent progress of research on color-coded pathways in nonprimate dichromats to identify differences or similarities between di- and trichromatic mammals. In addition, we applied immunohistochemical methods and confocal microscopy to retinas of different species and present data on their neuronal properties, which are expected to contribute to color vision. Basic neuronal features such as the “blue cone bipolar cell” exist in every species investigated so far. Moreover, there is increasing evidence for chromatic OFF channels in dichromats and retinal ganglion cells that relay color-opponent signals to the brain. In conclusion, di- and trichromats share similar retinal pathways for color transmission and processing.


1993 ◽  
Vol 10 (2) ◽  
pp. 353-361 ◽  
Author(s):  
Bruce Yazejian ◽  
Gordon L. Fain

AbstractWe have recorded whole-cell membrane currents in response to exogenously applied acetylcholine (ACh), nicotine, and 1,1 dimethyl-4-phenyl piperazinium iodide on retinal ganglion cells enzymatically dissociated from goldfish retina. Agonist applications induced nicotinic-type responses in a majority of cells when cells were isolated under optimal conditions. Currents were reminiscent of nicotinic-type ganglionic responses. Dose-response measurements of ACh-induced currents indicated an EC50 of 52 μM and a Hill coefficient of 0.6. Currents were selective for Na+ over Cl− and were highly inwardly rectifying. Responses were blocked reversibly by d-tubocurarine, hexamethonium chloride, and N-methyl-D-glucamine. In 50% of the cases, α-bungarotoxin reversibly blocked the current induced by ACh application. The blocking action of mecamylamine was irreversible and independent of the presence of agonist but was more effective in the presence of ACh. We conclude that functional nicotinic ACh receptors exist on most goldfish retinal ganglion cells.


2007 ◽  
Vol 24 (4) ◽  
pp. 503-511 ◽  
Author(s):  
J.M. RENNA ◽  
C.E. STRANG ◽  
F.R. AMTHOR ◽  
K.T. KEYSER

Strychnine is considered a selective competitive antagonist of glycine gated Cl− channels (Saitoh et al., 1994) and studies have used strychnine at low micromolar concentrations to study the role of glycine in rabbit retina (Linn, 1998; Protti et al., 2005). However, other studies have shown that strychnine, in the concentrations commonly used, is also a potent competitive antagonist of α7 nicotinic acetylcholine receptors (nAChRs; Matsubayashi et al., 1998). We tested the effects of low micromolar concentrations of strychnine and 3-[2′-phosphonomethyl[1,1′-biphenyl]-3-yl] alanine (PMBA), a specific glycine receptor blocker (Saitoh et al., 1994; Hosie et al., 1999) on the activation of both α7 nAChRs on retinal ganglion cells and on ganglion cell responses to a light flash. Extracellular recordings were obtained from ganglion cells in an isolated retina/choroid preparation and 500 μM choline was used as an α7 agonist (Alkondon et al., 1997). We recorded from brisk sustained and brisk transient OFF cells, many of which have been previously shown to have α7 receptors (Strang et al., 2005). Further, we tested the effect of strychnine, PMBA and α-bungarotoxin on the binding of tetramethylrhodamine α-bungarotoxin in the inner plexiform layer. Our data indicates that strychnine, at doses as low as 1.0 μM, can inhibit the α7 nAChR-mediated response to choline, but PMBA at concentrations as high as 0.4 μM does not. Binding studies show strychnine and α-bungarotoxin inhibit binding of labeled α-bungarotoxin in the IPL. Thus, the effects of strychnine application may be to inhibit glycine receptors expressed by ganglion cell or to inhibit amacrine cell α7 nAChRs, both of which would result in an increase in the ganglion cell responses. Further research will be required to disentangle the effects of strychnine previously believed to be caused by a single mechanism of glycine receptor inhibition.


2005 ◽  
Vol 289 (3) ◽  
pp. C644-C655 ◽  
Author(s):  
Christianne E. Strang ◽  
Margot E. Andison ◽  
Franklin R. Amthor ◽  
Kent T. Keyser

It is well known that cholinergic agents affect ganglion cell (GC) firing rates and light responses in the retinas of many species, but the specific receptor subtypes involved in mediating these effects have been only partially characterized. We sought to determine whether functional α7 nicotinic acetylcholine receptors (nAChRs) contribute to the responses of specific retinal GC classes in rabbit retina. We used electrophysiology, pharmacology, immunohistochemistry, and reverse transcriptase-polymerase chain reaction to determine the pharmacological properties and expression of nAChR subtypes by specific rabbit retinal GC classes. Choline was used as an α7 nAChR agonist. Methyllycaconitine (MLA) was used as a competitive α7 nAChR antagonist. The application of choline before synaptic blockade resulted in changes in retinal GC activity, including increases or decreases in maintained firing and/or enhancement or suppression of light responses. Many physiologically identified GC types, including sustained off, sustained on, transient off, and transient on cells, demonstrated responses to choline application while under synaptic blockade. The choline-induced responses could be blocked with MLA, confirming α7 nAChR activation. Individual choline-responsive GCs displayed mRNA transcripts consistent with the expression of functional α7 nAChRs. Other GCs demonstrated physiological responses and mRNA expression consistent with the expression of both α7 and non-α7 nAChRs. Thus mRNA is present for multiple nAChR subunits in whole retina extracts, and functional α7 nAChRs are capable of modulating the responses of GCs in adult rabbit retina. We also demonstrate through physiological responses that subsets of GCs express more than one nAChR subtype.


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