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PubMed1975

[The effect of acetylcholine on the membrane potential of goldfish retina horizontal cells and the frog electroretinogram].

The effect of acetylcholine was studied as applied to horizontal cells of the goldfish retina and frog electroretinogram ACh (1-10-9--1-10-3 M) depolarized the cells. The highest level of depolarization never reached the O-level of the membrane potential and was approximately equal to the membrane potential in the dark. ACh (1-10-2--5-10-2 M) inhibited b- and d-waves and revealed the stable PIII component. It is supposed that ACh may be a transmitter in retinal outer synpatic layer.

Acetylcholine↗

PubMed2003

Localization of GABAA receptor subunits alpha 1, alpha 3, beta 1, beta 2/3, gamma 1, and gamma 2 in the salamander retina.

Electrophysiological studies have demonstrated that gamma-aminobutyric acid receptors type A (GABA(A)) mediate important information processing in the retinas of salamander and other vertebrates. The pharmacology and physiology of GABA(A) receptors depend on their subunit composition. We studied the localization of GABA(A) receptor subunit isoforms alpha(1), alpha(3), beta(1), beta(2/3) (antibody BD-17 and 62-3G1), gamma(1), and gamma(2) in salamander retina with immunocytochemical methods. All three beta-subunit antibodies labeled similarly in the outer retina, especially the inner segments and synaptic terminals of rod photoreceptors (identified with protein kinase C). Somatic labeling was observed in cell bodies of some horizontal cells, bipolar cells, amacrine cells, and cells in the ganglion cell layer (GCL). Puncta were present throughout the inner plexiform layer (IPL) for beta(1) and 62-3G1, but not for BD-17. alpha(1)-immunoreactivity (IR) stained a population of presumed OFF rod-dominated bipolar cells, including dendrites, soma, and axon terminals in the distal IPL. A subtype of GABAergic amacrine cell also expressed alpha(1)-IR, with puncta sparsely distributed at the distal and proximal margins of the IPL. Both the OPL and IPL were labeled throughout for alpha(3)-IR, as opposed to the narrow distribution of alpha(1)-IR in the IPL, suggesting that the two alpha-subunits are localized at different synaptic sites. Punctate gamma(1)-IR was observed in the OPL and IPL, whereas gamma(2) was most prominent in cone photoreceptors (identified with calbindin), including the terminal telodendria, in cell bodies of some horizontal cells, amacrine cells, cells in the GCL, and less intensely in the IPL. In addition, several subunits were present in Müller cells. The differential labeling suggests the existence of GABA(A) receptor subtypes with different subunit compositions that mediate multiple GABAergic functions in salamander retina.

Ambystoma↗

PubMed1981

The distribution of neurons projecting from the retina and visual cortex to the thalamus and tectum opticum of the barn owl, Tyto alba, and the burrowing owl, Speotyto cunicularia.

Using the HRP retrograde transport technique in two different genera of owls (Speotyto and Tyto), we have studied the distribution of neurons projecting to the optic tectum and the visual thalamus. Small injections of HRP were made into these structures from the pial surface after they had been visualized directly by dissection of the overlying bone. In contrast to the findings in mammals, retinal ganglion cells were labeled only in the eye contralateral to the injection site, whether this was in the thalamus or tectum, and the labeled ganglion cells were found on both nasal and temporal sides of the vertical retinal meridian through the fovea. After thalamic injections, labeling was prominent in temporal retina representing the binocular field, temporal to the optic nerve head. Retinothalamic ganglion cells formed roughly concentric lines of isodensity centered on the fovea (Speotyto) or area centralis (Tyto); labeling from thalamic injections involved both large and medium-sized neurons, but did not involve the smallest nor a conspicuous class of very large neurons. Tectal injections led to prominent labeling along the horizontal streak region, with horizontally elongated isodensity contours in both Tyto and Speotyto; retinotectal ganglion cells were heterogeneous and included a group of very large neurons and anther group of small neurons, neither of which was labeled from the thalamus. In the visual Wulst, labeled neurons were confined to the supragranular layers after both tectal and thalamic injections. Corticotectal neurons were found in both ipsilateral and contralateral visual Wulst. They were characterized by large cell bodies and prominent dendrites. Corticotectal neurons were distributed throughout the mediolateral extent of the ipsilateral Wulst and therefore involved both the monocular and binocular representations of the visual field. Corticothalamic neurons, found only in the ipsilateral Wulst, were characterized by smaller cell bodies and fine dendrites. They were confined to the monocular crescent on the extreme medial edge of the World.

Animals↗

PubMed2001

See-saw nystagmus and congenital nystagmus identified in the non-decussating retinal-fugal fiber syndrome.

PURPOSE: The purpose of the present study was to accurately document the oculomotor misalignments and instabilities associated with the non-decussating retinal-fugal fiber syndrome, a rare inborn, isolated, achiasmatic condition. To date, the achiasmatic syndrome described has thus far been identified in three unrelated females. A comparable achiasmatic condition has also been identified in a canine breed. MATERIALS AND METHODS: The unique, inborn visual pathway malformation in the form of an isolated absence of the optic chiasm was confirmed by metabolic assay, the visual evoked potential (VEP) misrouting paradigm and neuroradiological evaluation, including magnetic resonance imaging (MRI). Horizontal and vertical, left and right eye, oculomotor scleral search coil recordings were measured, in one of the achiasmats, at 15 years of age. Comparable oculomotor recordings were implemented in three controls, including a normal age-matched control, an adult control and an adult with idiopathic congenital nystagmus (CN). In addition to central and eccentric target fixation with binocular and monocular viewing, binocular and monocular pursuit and optokinetic nystagmus (OKN) also were recorded. RESULTS: Following a binocular and monocular fixation paradigm, classic congenital nystagmus (CN) profiles were recorded in the achiasmat in the horizontal planes together with see-saw nystagmus (SSN) in the vertical planes; an alternating esotropia and vertical tropias also were documented. The CN showed interocular conjugacy and waveforms typically exhibited well-defined foveation periods. In general, both achiasmatic horizontal and vertical eye movements as well as corresponding interocular misalignments varied with stimu-lus and recording conditions. Moreover, horizontal eye movements showed sustained interocular conjugacy while vertical eye movements typically showed disconjugacy. Previous oculomotor studies in the achiasmatic canine breed revealed comparable oculomotor instabilities, albeit the latter were reported to present primarily with unyoked eye movements and uniocular saccades. In the present study, in addition to target fixation with binocular and monocular viewing, binocular and monocular pursuit and OKN responses also were recorded. For the achiasmat, high-gain pursuit results, as with eccentric fixation, emphasized a preference for fixation with the adducting eye. Also at eccentric gaze with monocular viewing, the eye under cover showed, relative to the fixating eye, a hypodeviation concomitant with adduction and a hyperdeviation concomitant with abduction. OKN profiles in the achiasmat with stimuli presented under both normal viewing and open-loop, retinal-field locked conditions proved rather complex; however, when an OKN response was identified, reversed OKN tracking was not apparent. CONCLUSIONS: In general, the oculomotor results reported herein demonstrate that the non-decussating retinal-fugal fiber syndrome is an afferent visual pathway disorder associated with vertical and horizontal misalignments concurrent with congenital nystagmus and also with the rarer see-saw nystagmus.

Adolescent↗

PubMed1993

Horizontal cells of the normal and dystrophic rat retina: a wholemount study using immunolabelling for the 28-kDa calcium-binding protein.

Immunocytochemistry with a monoclonal antibody against the 28-kDa calcium-binding protein (28-kDa CaBP) was used to study horizontal cells in both congenic control (RCS-rdy+) and dystrophic (RCS) 3-month-old rat retina. We found that horizontal cells in the RCS-rdy+ rat retinas were distributed evenly from the centre to the peripheral retina with a mean density of 783 cells mm-2. Cell size ranged between 6.5-12.5 microns in diameter with a mean of 8.87 microns. Individual cell processes could not be followed readily, however they formed a narrow plexus within the outer plexiform layer with the primary dendrites extending radially from each cell soma in an organized manner. In the RCS rat, by contrast, the horizontal cell processes were more disorganized than in the congenic controls. The degree of disorganization varied across the retina. In the posterior pole, where all outer layers had been lost, many processes were grossly swollen along their length and at the tips. The cell somas were also distributed more widely in the depth of the retina. In the peripheral retina, where a debris layer was still present, the processes were less swollen but they extended abnormally widely in depth. Despite the disorganized structure the mean and range of cell size (9.23 microns, 5.5-15.5 microns), and cell density (796 cells mm-2) were similar to that of the control RCS-rdy+ animals. These findings indicate that in dystrophic retinas beyond a certain stage of degeneration the horizontal cells become abnormal in their structure but are present at a normal density and the somas are not grossly swollen or shrunken.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1999

Astrocyte proliferation during development of the human retinal vasculature.

Wholemounts of human fetal retinas were labeled with antibodies to Ki67 or proliferating cell nuclear antigen, to map the distribution of proliferating cells in the developing primary vasculature and neural retina. Double labeling was used to determine the relative proportions of endothelial cells (CD34), astrocytes (glial fibrillary acidic protein - GFAP) and microglia (major histocompatability complex class II) associated with the developing vessels. The differentiated region of neural retina (cold spot) was 3.5 mm(2)at 15 weeks gestation (WG), centred on the incipient fovea, and increased in size with age to 80.5 mm(2)by 23-24 WG. Ki67 immunoreactive cells were distributed throughout the developing vasculature at all ages. The mean density of dividing cells in the neural retina increased with gestational age from 146 mm(-2)at 15 WG, to 624 mm(-2)at 23-24 WG. By 20 WG proliferation in the vasculature overlapped the margins of the cold spot, which was almost completely vascularized by 23-24 WG, except for a narrow strip on the horizontal meridian, which included the incipient fovea. Counts of CD34/Ki67 immunoreactive cells indicated that 15-52% of proliferations in the developing vasculature at 18 WG are endothelial cells. In contrast, in the fellow retina 65-85% cells were Ki67/GFAP immunoreactive, indicating proliferation of astrocytes in situ. No dividing microglia were observed. The findings suggest that large numbers of proliferating astrocytes accompany the developing vessels as they migrate across the primate retina.

Antigens, CD34↗

PubMed1999

Effects of the neurotrophin brain-derived neurotrophic factor in an experimental model of retinal detachment.

PURPOSE: To examine the effects of brain-derived neurotrophic factor (BDNF) in an animal model of retinal detachment. METHODS: Cat retinas were detached from the retinal pigment epithelium for either 7 or 28 days. Animals received either an intravitreal injection of BDNF (100 ILg) or phosphate-buffered saline (PBS), the vehicle for BDNF. Retinas were evaluated using morphology and immunocytochemistry. The width of the outer segment zone was measured, and the retinas were evaluated for changes in protein expression by labeling with antibodies to rod opsin, phosducin, synaptophysin, calbindin D, and glial fibrillary acidic protein (GFAP). The effect of BDNF on both proliferation and apoptotic cell death was examined. RESULTS: Although there was variability in the treated retinas, most of the animals receiving BDNF had well-organized outer segments that were longer than those in vehicle-treated controls. Immunocytochemistry revealed that treated retinas had consistently less opsin redistribution to the plasma membrane, less phosducin upregulation, and fewer calbindin D-labeled horizontal cell processes. BDNF did not reduce overall cell death in the detachments or death of photoreceptors by apoptosis. However, it significantly reduced the proliferative response of Miller cells and the extent of upregulation of GFAP. CONCLUSIONS. The results suggest that BDNF may aid in the recovery of the retina after reattachment by maintaining the surviving photoreceptor cells, by reducing the gliotic effects in Müller cells, and perhaps by promoting outer segment regeneration.

Animals↗

PubMed1981

Lectin receptors on cells isolated from the turtle retina.

The presence of specific oligosaccharides on the surface of retinal cells was examined by incubating FITC-labeled lectins with cells dissociated from papain-treated turtle retinas. The pattern and intensity of binding was found to vary among the cells examined. With Con A, there was strong surface staining of both rods and cones, with an intense ring of fluorescence above the nucleus. The bipolar and ganglion cells also showed strong surface labeling. In Müller (glial) cells there was intense fluorescence in the apical, microvillous region. In contrast, the horizontal cells and their axons showed weak staining. When RCA-60, RCA-120, and WGA were incubated with photoreceptors, bipolar cells, or horizontal cells, little fluorescence was visible. However, all three lectins bound strongly to the Müller cells. In contrast, the Lotus lectin did not bind to any of the cells examined. In all the cases, lectin binding was inhibited by the appropriate haptene sugar. Further, prior treatment cells with neuraminidase did not alter lectin binding to any cell type. These results suggest differences in the distribution of lectin receptors among specific cell types, and particularly between neurons and glial cells in the vertebrate retina.

Animals↗

PubMed2006

Retinoids, eye development, and maturation of visual function.

Vitamin A is known to be critical for the beginning of eye development as well as for photoreception in the functional retina. Hardly anything, however, is known about whether retinoic acid (RA)-regulated gene expression also plays a role in the long intervening period, during which the neurobiological retinal structure takes shape. The eye contains a highly intricate architecture of RA-synthesizing (RALDH) and degrading (CYP26) enzymes. Whereas the RALDHs are integrated in the early molecular mechanisms through which the dorso-ventral retina organization is established, the CYP26 enzymes are not necessary for this process and no molecular targets that match their retinal expression pattern have yet been identified. In this article we describe that CYP26 expression in the mouse is most distinctive during later stages of retina formation. Throughout development CYP26A1 degrades RA in a horizontal region that extends across the retina, but during later embryonic and postnatal retina maturation this function is reinforced by another enzyme, CYP26C1. RA applications at this stage do not affect the RALDHs but cause differential changes in CYP26 expression: Cyp26a1 is up-regulated, but more rapidly by 9-cis than all-trans RA, Cyp26c1 is down-regulated, and Cyp26b1, which is undetectable in the normal mouse retina, is strongly activated in retinal ganglion cells. The dynamic regulation in RA-difference patterns by the CYP26 enzymes may set up spatial constellations for expression of genes involved in formation of retinal specializations for higher acuity vision, which are known to form over a prolonged period late in retina development.

Aldehyde Oxidoreductases↗

PubMed1988

Behavior of floccular Purkinje cells correlated with adaptation of horizontal optokinetic eye movement response in pigmented rabbits.

Single unit spike activities of Purkinje cells in the cerebellar flocculus were examined during sustained horizontal sinusoidal oscillation (0.33 Hz, 2.5 degrees peak-to-peak) of a striped screen around an alert pigmented rabbit. The floccular area specifically related to horizontal reflex eye movement (H-zone) was identified by means of local stimulation that induced abduction of the ipsilateral eye. In control states, simple spike discharge of most of the H-zone Purkinje cells was enhanced by backward screen movement and depressed by forward screen movement, while complex spike discharge was modulated reciprocally. After one-hour sustained oscillation of the screen, the gain of horizontal optokinetic eye movement response (HOKR) increased by 0.16 on average. Correspondingly, simple spike modulation in most of H-zone Purkinje cells tested significantly increased in amplitude, while complex spike modulation tended to decrease. No such systematic changes were observed in other Purkinje cells. These results are consistent with the hypothesis that the floccular H-zone Purkinje cells adaptively control the optokinetic eye movement through modification of the visual mossy fiber responsiveness under the influence of the retinal error signals conveyed by the visual climbing pathway.

Action Potentials↗

PubMed1996

The occurrence of protein kinase C theta and lambda isoforms in retina of different species.

The localization and immunochemical identification of the novel protein kinase C theta (nPKC theta) and the atypical protein kinase C lambda (aPKC lambda) isoforms in retinas of different species were analyzed by immunohistochemistry and SDS-PAGE/Western blotting. nPKC theta immunoreactivity is associated with bipolar cells of mammalian (rabbit, rat and guinea pig) retinas but not the non-mammalian goldfish retina which has a lower concentration of nPKC theta. However, SDS-PAGE and Western blotting data indicate the antigen recognized by the nPKC theta monoclonal antibody in the retina is of a lower molecular weight than that expected for nPKC theta. This would suggest nPKC theta is more susceptible to degradation/breakdown than other PKC isoforms found in the retina or that the nPKC theta antibody may be recognizing an unknown retinal antigen. A comparison of nPKC theta and cPKC alpha immunoreactivities in bipolar cells shows unique distributions exist for the two isoforms. nPKC theta is present in the developing retina at an earlier stage than cPKC alpha. The typical 'transport' of cPKC alpha toward axonal terminals by phorbol-12,13-dibutyrate does not occur for nPKC theta yet both are translocated from the cytosolic to membrane compartments. The inner plexiform layer and the inner nuclear layer (putative horizontal cells) of all species examined (rabbit, rat, guinea pig and goldfish) exhibited positive immunoreactivity for aPKC lambda as confirmed by SDS-PAGE/Western blotting.

Animals↗

PubMed1996

Clearance of neurotransmitter from the cone synaptic cleft in goldfish retina.

Dendrites of bipolar and horizontal cells protrude deeply into the synaptic terminals of cones in goldfish retina. This arrangement gives the impression that the cone synaptic terminal surrounds a morphologically shielded compartment, the cone synaptic cleft, from which clearance of neurotransmitter by diffusion is limited. In this study the time constant of this clearance has been approached in two ways: (1) the morphological parameters determining the clearance (extracellular synaptic volume and leak area), were estimated using morphometric methods. These data were introduced into a diffusion model of the cone pedicle, yielding a time constant for the clearance of < 1 msec; (2) the time constant of the light onset response when the glutamate transporter in the cone was blocked with DL-threo-beta-hydroxyaspartate or dihydrokainate, was interpreted as the time constant of the clearance, yielding values of almost 650 msec compared to around 90 msec in control conditions. The decay time-constant of the Ca-dependent tail-currents in cones was used, as an approximation of the dynamics of the intracellular Ca-concentration and thus of the glutamate release by the cones. The decay time constant was about 800 msec. This suggests that the intracellular Ca-concentration in the synaptic terminal and hence the glutamate release by the cones drops with a similar large time constant. These results indicate that the cone pedicle in goldfish does not limit the clearance of neurotransmitters from the synaptic cleft and that the fast light onset response of horizontal cells under control conditions is due to activation of glutamate transporters by hyperpolarization of the cone membrane potential while the glutamate release drops slowly. The slow horizontal cell light onset response in beta-hydroxyaspartate or dihydrokainate may be due to a slow reduction of the glutamate release by the cones at light onset.

Animals↗

PubMed1967

Receptive fields and trigger features of ganglion cells in the visual streak of the rabbits retina.

1. A survey of the properties of retinal ganglion cells in the central part of the rabbit retina has been carried out.2. The five types of unit previously encountered in the peripheral retina were also found in the central region. Their receptive fields were smaller, and tended to be oval-shaped with the long axis horizontal.3. In addition, three new types were discovered: orientation-selective cells, local-edge-detectors, uniformity-detectors.4. Orientation-selective cells were sensitive to either vertically or horizontally extended targets. Analysis suggested they were modified concentric units with an incomplete antagonistic surround.5. Local-edge-detectors responded to the appearance or movement of a contrasting border within the receptive field. They were inhibited by similar stimulation of the region surrounding the receptive field. Detailed attention was given to the demonstration of edge-detection.6. Uniformity detectors had a relatively high level of ongoing activity in the absence of stimulation. All forms of stimulation (lights flashed on or off, movement of darker or lighter targets) produced a diminution or cessation of ongoing activity.7. The results are compared with behaviour described in other species.

Animals↗

PubMed1975

Interactions of rod and cone signals in the mudpuppy retina.

Interactions between rod and cone signals in mudpuppy retinal neurones were investigated by intracellular recording. 2. The mudpuppy retina contains one kind of rod (lambda max = 525 nm) and one kind of cone (lambda max = 572 nm). The responses of receptors can be distinguished on the basis of their spectral sensitivities. 3. Rod and cone responses have different time courses of recovery and absolute sensitivities. Differences between receptor responses can be used to describe inputs to interneurones. 4. There are two spectral classes of horizontal cells: L-type and C-type. L-type cells are hyperpolarized by rods and cones in varying proportion, with some cells receiving little rod input. C-type cells are hyperpolarized by rods and depolarized by cones. 5. Bipolar cell receptive field centres receive input from cones or from rods and cones. There is no correlation between the spectral properties of centre responses and their polarity. 6. Antagonistic surrounds of bipolar cells show cone or rod and cone sensitivity. They are believed to be generated by the L-type horizontal cells. 7. Some bipolar cells exhibit chromatic interactions between cone signals in the centre and rod signals in the surround, which resemble those observed between the signals of different spectral classes of cones in species known to possess colour discrimination. 8. Amacrine and on-off ganglion cells have L-type responses showing both rod and cone sensitivity. 9. It is proposed that interactions between rod and cone signals observed in mudpuppy also exist in primate retina and are at least partially responsible for certain psychophysical observations of rod-cone interactions.

Animals↗

PubMed2006

Immunohistochemical evidence of a melanopsin cone in human retina.

PURPOSE: Melanopsin, expressed in a subset of intrinsically photosensitive ganglion cells that project to the suprachiasmatic nucleus (SCN), is involved in the photic entrainment of circadian rhythms and other non-image-forming functions (pupil light reflex, masking, acute heart rate response, and alertness). Melanopsin has recently been shown to be a "bireactive" photopigment that functions as a photosensory opsin using 11-cis retinaldehyde as a chromophore and has intrinsic photoisomerase activity. Melanopsin is widely distributed in the retina of vertebrates and, depending on the species, is expressed in ganglion, amacrine, horizontal, and photoreceptor cells. The present study was conducted to determine the distribution of this opsin in the human retina. METHODS: Human donor eyes were obtained from donors and fixed shortly after death. Immunohistochemistry was used to determine melanopsin expression in the retinas of three donors. The possible coexpression of this photopigment with other opsins was studied by double-labeling immunocytochemistry and confocal analysis. RESULTS: In addition to the expected labeling in ganglion cells of the inner retinal layers, an unexpected finding showed melanopsin-immunopositive label in the outer segments of cones that did not coexpress other known opsins. These melanopsin-expressing cones are extremely sparse (5-25 cones/mm2; 0.1%-0.5% of the entire cone population) and are located in the peripheral retina. CONCLUSIONS: The presence of melanopsin in human cones suggests image and non-image-forming roles in visual responses at both the cone input and ganglion cell output stages and their involvement in a broad spectrum of irradiance detection functions in the visual system.

Adult↗

PubMedDate not supplied

Cellular organization in retinal transplants using cell suspensions or fragments of embryonic retinal tissue.

We have investigated the cellular organization in two different types of retinal transplants using cell type-specific monoclonal antibodies. Both fragments and cell suspensions of E17-E19 Sprague-Dawley rat retina were transplanted to a subretinal site in congenic adult rat hosts. After a survival time of 28 days, the transplants were stained by immunocytochemistry with antibodies against rhodopsin, which stained rods; with antibodies against HPC-1, which stained amacrine cells and outer and inner plexiform layers; and with antibodies against vimentin, which stained Müller cell fibers and horizontal cells. In the host retina, the distribution of immunocytochemical staining was similar, irrespective of transplantation technique. In the transplants, the anti-rhodopsin staining showed that fragment transplants developed photoreceptors in rosettes, whereas in cell suspension transplants, this staining showed a scattered distribution of photoreceptors. The HPC-1 staining showed that regions corresponding to the inner nuclear layer surrounded both types of transplants and made large invaginations into them. In one case, using the cell suspension technique, fibres were found to run from the inner plexiform layer of the transplant to the outer plexiform layer of the host. The vimentin staining revealed a disorganized array of Müller cell fibres in both types of transplants, but with some concentration to the regions corresponding to the inner plexiform layer.

Animals↗

PubMed2000

Autoradiographic distribution of peripheral benzodiazepine receptors in the retina of the albino rabbit, Lepus cunicula.

The distribution of peripheral benzodiazepine receptors (PBRs) in the retina of the albino rabbit, Lepus cunicula, was studied by autoradiography using [3H]-PK11195, a isoquinoline carboxamide, as a tracer. Autoradiograms obtained by directly placing the slides containing the retina sections on tritium-sensitive film provide evidence for the presence of PBRs in rabbit retina. Furthermore, the dark field examination of photomicrographs taken from autoradiograms showed two dense horizontal bands corresponding to the outer and inner photoreceptor segments, and to the inner plexiform layer. The retinal regions where [3H]-PK11195 binding was more dense are rich in mitochondria, suggesting that as in other neuronal tissues, retinal PBRs are involved in the mitochondrial activity.

Animals↗

PubMed2001

A dopamine- and protein kinase A-dependent mechanism for network adaptation in retinal ganglion cells.

Vertebrates can detect light intensity changes in vastly different photic environments, in part, because postreceptoral neurons undergo "network adaptation." Previous data implicated dopaminergic, cAMP-dependent inhibition of retinal ganglion cells in this process yet left unclear how this occurs and whether this occurs in darkness versus light. To test for light- and dopamine-dependent changes in ganglion cell cAMP levels in situ, we immunostained dark- and light-adapted retinas with anti-cAMP antisera in the presence and absence of various dopamine receptor ligands. To test for direct effects of dopamine receptor ligands and membrane-permeable protein kinase ligands on ganglion cell excitability, we recorded spikes from isolated ganglion cells in perforated-patch whole-cell mode before and during application of these agents by microperfusion. Our immunostainings show that light, endogenous dopamine, and exogenous dopamine elevate ganglion cell cAMP levels in situ by activating D1-type dopamine receptors. Our spike recordings show that D1-type agonists and 8-bromo cAMP reduce spike frequency and curtail sustained spike firing and that these effects entail protein kinase A activation. These effects resemble those of background light on ganglion cell responses to light flashes. Network adaptation could thus be produced, to some extent, by dopaminergic modulation of ganglion cell spike generation, a mechanism distinct from modulation of transmitter release onto ganglion cells or of transmitter-gated currents in ganglion cells. Combining these observations with results obtained in studies of photoreceptor, bipolar, and horizontal cells indicates that all three layers of neurons in the retina are equipped with mechanisms for adaptation to ambient light intensity.

8-Bromo Cyclic Adenosine Monophosphate↗