Responses of neurones of the rat suprachiasmatic nucleus to retinal illumination under photopic and scotopic conditions.
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1. We have examined the responses of neurones in the suprachiasmatic nuclei (SCN) of the rat to retinal illumination under photopic and scotopic conditions to identify the types of photoreceptor input to these nuclei. 2. The majority of visually responsive SCN neurones studied under dark adaptation received rod input (48 of 52, 92 %). The action spectrum conformed to the sensitivity of rhodopsin, with maximal sensitivity at around 505 nm. 3. When also studied under light adaptation, most visually responsive SCN neurones (20 out of 26, 77 %) responded to input from cones. The action spectra conformed to the spectrum of green cone opsin, with a main sensitivity peak at 510 nm and a significant secondary peak in the near-ultraviolet region of the spectrum. 4. The frequency of spontaneous activity was typically low under scotopic conditions (range 0.2-17.2 Hz) and higher under photopic conditions (range 0.6-40 Hz) for any given neurone. The most common response under scotopic conditions was an 'on-excitation' (32 of 48, 62.5 %), which changed under photopic conditions to an on-excitation followed by a more prominent off-inhibition. 5. Responses also changed due to endogenous ultradian cycles. Depending on the phase, responses could be altogether absent and even reverted from excitation to inhibition on opposite phases of a cycle. Ultradian cycles had a circadian dependence and were most common at around the light phase:dark phase (L:D) and D:L transition points of the circadian cycle. 6. Under photopic conditions, SCN neurones showed rhythmic electrical activity, with a preferred firing interval that had a value between 18 and 39 ms. This rhythmic activity was probably the result of endogenous subthreshold membrane potential oscillations. 7. In conclusion, light acting either via rod or cone pathways could have powerful, opposing actions on SCN neurones. These actions were state dependent. The presence of these neuronal responses suggests a role for rod and cone photoreceptors in SCN function. (+info)
Calcium transients in the rhabdomeres of dark- and light-adapted fly photoreceptor cells.
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The light response of fly photoreceptor cells is modulated by changes in free Ca(2+) concentration. Fly phototransduction and most processes regulating it take place in or very close to the rhabdomere. We therefore measured the kinetics and the absolute values of the free Ca(2+) concentration in the rhabdomere of fly photoreceptor cells in vivo by making use of the natural optics of the fly's eye. We show that Ca(2+) flowing into the rhabdomere after light stimulation of dark-adapted cells causes fast Ca(2+) transients that reach peak values higher than 200 microM in <20 msec. Approximately 500 msec later, the free Ca(2+) concentration has declined again to approximately 20 microM. The duration of the Ca(2+) transients becomes still shorter, and their size reduced, when the photoreceptor cell is light-adapted. This reduction in duration and size of the Ca(2+) transients is graded with the intensity of the adapting light. The kinetics and absolute values of the free calcium concentration found to occur in the rhabdomere are suitable to mediate the fast feedback signals known to act on the fly phototransduction cascade. (+info)
Disruption of the olfactoretinal centrifugal pathway may relate to the visual system defect in night blindness b mutant zebrafish.
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We describe here a dominant mutation, night blindness b (nbb), which causes an age-related visual system defect in zebrafish. At 4-5 months of age, dark-adapted nbb(+/-) mutants show abnormal visual threshold fluctuations when measured behaviorally. Light sensitizes the animals; thus early dark adaptation of nbb(+/-) fish is normal. After 2 hr of dark adaptation, however, visual thresholds of nbb(+/-) mutants are raised on average 2-3 log units, and rod system function is not detectable. Electroretinograms recorded from nbb(+/-) mutants are normal, but ganglion cell thresholds are raised in prolonged darkness, suggesting an inner retinal defect. The visual defect of nbb(+/-) mutants may be likely caused by an abnormal olfactoretinal centrifugal innervation; in nbb(+/-) mutants, the olfactoretinal centrifugal projection to the retina is disrupted, and the number of retinal dopaminergic interplexiform cells is reduced. A similar visual defect as shown by nbb(+/-) mutants is observed in zebrafish in which the olfactory epithelium and olfactory bulb have been excised. Homozygous nbb fish display an early onset neural degeneration throughout the CNS and die by 7-8 d of age. (+info)
Effects of dopamine depletion on visual sensitivity of zebrafish.
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The visual sensitivity of zebrafish in which the retinal dopaminergic interplexiform cells (DA-IPCs) were destroyed by 6-hydroxydopamine was measured behaviorally. During the first 6-8 min of dark adaptation, visual thresholds of DA-IPC-depleted animals were similar to those of control animals. Thereafter, their visual thresholds were elevated so that by 14-18 min of dark adaptation, they were 2-3 log units above those of control animals. In DA-IPC-depleted animals, the electroretinogram was normal in terms of light sensitivity and waveform, but the light threshold for eliciting a ganglion cell discharge was raised by 1.8 log units as compared with control animals. No obvious rod system function was detected in DA-IPC-depleted animals as measured behaviorally. Partial rescue of the behavioral visual sensitivity loss in DA-IPC-depleted animals occurred when dopamine or a long-acting dopamine agonist (2-amino-6, 7-dihydroxy-1, 2, 3, 4-tetrahydronaphthalene hydrobromide) were injected intraocularly. Our data suggest that the principal visual defect shown by DA-IPC-depleted animals is attributable to effects occurring in the inner retina, mainly on rod signals. We also show that dopamine is involved in mediating the effect of the circadian clock on visual sensitivity. (+info)
Mice lacking G-protein receptor kinase 1 have profoundly slowed recovery of cone-driven retinal responses.
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G-Protein receptor kinase 1 (GRK1) ("rhodopsin kinase") is necessary for the inactivation of photoactivated rhodopsin, the light receptor of the G-protein transduction cascade of rod photoreceptors. GRK1 has also been reported to be present in retinal cones in which its function is unknown. To examine the role of GRK1 in retinal cone signaling pathways, we measured in mice having null mutations of GRK1 (GRK1 -/-) cone-driven electroretinographic (ERG) responses, including an a-wave component identified as the field potential generated by suppression of the circulating current of the cone photoreceptors. Dark-adapted GRK1 -/- animals generated cone-driven ERGs having saturating amplitudes and sensitivities in both visible and UV spectral regions similar to those of wild-type (WT) mice. However, after exposure to a bright conditioning flash, the cone-driven ERGs of GRK1 -/- animals recovered 30-50 times more slowly than those of WT mice and similarly slower than the cone-driven ERGs of mice homozygously null for arrestin (Arrestin -/-), whose cone (but not rod) response recoveries were found to be as rapid as those of WT. Our observations argue that GRK1 is essential for normal deactivation of murine cone phototransduction and provide the first functional evidence for a major role of a specific GRK in the inactivation of vertebrate cone phototransduction. (+info)
Light evokes Ca2+ spikes in the axon terminal of a retinal bipolar cell.
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Bipolar cells in the vertebrate retina have been characterized as nonspiking interneurons. Using patch-clamp recordings from goldfish retinal slices, we find, however, that the morphologically well-defined Mb1 bipolar cell is capable of generating spikes. Surprisingly, in dark-adapted retina, spikes were reliably evoked by light flashes and had a long (1-2 s) refractory period. In light-adapted retina, most Mb1 cells did not spike. However, an L-type Ca2+ channel agonist could induce periodic spiking in these cells. Spikes were determined to be Ca2+ action potentials triggered at the axon terminal and were abolished by 2-amino-4-phosphonobutyric acid (APB), an agonist that mimics glutamate. Signaling via spikes in a specific class of bipolar cells may serve to accelerate and amplify small photo-receptor signals, thereby securing the synaptic transmission of dim and rapidly changing visual input. (+info)
The retina of c-fos-/- mice: electrophysiologic, morphologic and biochemical aspects.
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PURPOSE: Mice without a functional c-Fos protein (c-fos-/- mice) do not exhibit light-induced apoptotic cell death of rods in contrast to their wild-type littermates (c-fos+/+ mice). To analyze the consequences of the absence of c-fos in the retina, we investigated whether the retinas of c-fos-/- mice have a reduced capacity to absorb and transduce light compared with c-fos+/+ mice. METHODS: Retinal function was evaluated in dark-adapted mice by full-field electroretinograms (ERGs) over more than 6 log units of intensity. Retinal morphology was studied by light- and electron microscopy. Arrestin and the heat shock protein 70 (Hsp70) were detected by Western blot analysis. The rhodopsin content and the kinetics of rhodopsin regeneration were determined in retinal extracts. RESULTS: Although the configuration of the ERGs was comparable in both groups of mice, c-fos-/- mice showed a marked variability in all quantitative ERG-measures with lower mean amplitudes, longer latencies, and a 0.9-log-unit lower b-wave sensitivity on average. Morphometry showed that c-fos-/- mice have 23% fewer rods on average, whereas the number of cones was comparable among c-fos+/+ and c-fos-/- mice. Arrestin levels appeared slightly reduced in c-fos-/- mice when compared with c-fos+/+ mice, whereas Hsp70 levels were comparable in both genotypes. The kinetics of rhodopsin regeneration were similar, but c-fos-/- mice had a 25% lower rhodopsin content on average. CONCLUSIONS: Compared with c-fos+/+ mice, retinal function in c-fos-/- mice is attenuated to a variable but marked degree, which may be, at least in part, related to the reduced number of rods and the reduced rhodopsin content. However, c-fos does not appear to be essential for the ability to absorb photons, nor for phototransduction or the function of second-order neurons. The resistance to light-induced apoptosis of photoreceptor cells in c-fos-/- mice may result from the acute deficit of c-fos in the apoptotic cascade rather than from developmental deficits affecting rod photoreceptor function. (+info)
Surround inhibition of mammalian AII amacrine cells is generated in the proximal retina.
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1. Intracellular recordings were obtained from neurons in the superfused retina-eyecup preparation of the rabbit under dark-adapted conditions. Neurotransmitter agonists and antagonists were applied exogenously via the superfusate to dissect the synaptic pathways pharmacologically and thereby determine those pathways responsible for the generation of the on-centre/off-surround receptive fields of AII amacrine cells. 2. Application of the metabotropic glutamate receptor agonist, APB, reversibly blocked both the on-centre and off-surround responses of AII cells. These data were consistent with the idea that both the centre- and surround-mediated responses are derived from inputs from the presynaptic rod bipolar cells. 3. Whereas rod bipolar cells showed on-receptive fields approximately 100 microm across, we found no evidence for an antagonistic off-surround response using light stimuli which effectively elicited the off-surrounds of AII amacrine cells. These results indicated that the surrounds of AII cells are not derived from rod bipolar cell inputs. 4. Application of the ionotropic glutamate receptor antagonists CNQX or DNQX enhanced the on-centre responses of AII cells but attenuated the off-surround responses. These data indicated that the centre- and surround-mediated responses could not both be derived from signals crossing the rod bipolar-to-AII cell synapse. 5. Application of the glycine antagonist, strychnine, had only minor and variable effects on AII cell responses. However, the GABA antagonists picrotoxin and bicuculline enhanced the on-centre response but attenuated or completely blocked the off-surround response of AII cells. The GABA antagonists had no effect on the responses of horizontal cells indicating that their effects on AII cell responses reflected actions on inner retinal circuitry rather than feedback circuitry in the outer plexiform layer. 6. Application of the voltage-gated sodium channel blocker TTX enhanced the on-centre responses of AII cells but attenuated or abolished their off-surround responses. 7. Taken together, our results suggest that the on-centre responses of AII cells result from the major excitatory drive from rod bipolar cells. However, the surround receptive fields of AII cells appear to be generated by lateral, inhibitory signals derived from neighbouring GABAergic, on-centre amacrine cells. A model is presented whereby the S1 amacrine cells produce the surround receptive fields of AII amacrine cells via inhibitory, feedback circuitry to the axon terminals of rod bipolar cells. (+info)