Visual Neuroscience最新文献

Photoreceptors have high energy demands and densely packed mitochondria through which light passes before phototransduction. Old world primates including humans have three cone photoreceptor types mediating color vision with short (S blue), medium (M green), and long (L red) wavelength sensitivities. However, S-cones are enigmatic. They comprise <10% of the total cone population, their responses saturate early, and they are susceptible in aging and disease. Here, we show that primate S-cones actually have few mitochondria and are fueled by glycolysis, not by mitochondrial respiration. Glycolysis has a limited ability to sustain activity, potentially explaining early S-cone saturation. Mitochondria act as optical filters showing reduced light transmission at 400-450 nm where S-cones are most sensitive (420 nm). This absorbance is likely to arise in a mitochondrial porphyrin that absorbs strongly in the Soret band. Hence, reducing mitochondria will improve S-cone sensitivity but result in increased glycolysis as an alternative energy source, potentially increasing diabetic vulnerability due to restricted glucose access. Further, glycolysis carries a price resulting in premature functional decline as seen in aged S-cones. Soret band absorption may also impact on mitochondrial rich M and L cones by reducing sensitivity at the lower end of their spectral sensitivity range resulting in increased differentiation from S-cone responses. These data add to the list of unique characteristic of S-cones and may also explain aspects of their vulnerability.

At the first retinal synapse, horizontal cells (HCs) contact both photoreceptor terminals and bipolar cell dendrites, modulating information transfer between these two cell types to enhance spatial contrast and mediate color opponency. The synaptic mechanisms through which these modulations occur are still debated. The initial hypothesis of a GABAergic feedback from HCs to cones has been challenged by pharmacological inconsistencies. Surround antagonism has been demonstrated to occur via a modulation of cone calcium channels through ephaptic signaling and pH changes in the synaptic cleft. GABAergic transmission between HCs and cones has been reported in some lower vertebrates, like the turtle and tiger salamander. In these reports, it was revealed that GABA is released from HCs through reverse transport and target GABA receptors are located at the cone terminals. In mammalian retinas, there is growing evidence that HCs can release GABA through conventional vesicular transmission, acting both on autaptic GABA receptors and on receptors expressed at the dendritic tips of the bipolar cells. The presence of GABA receptors on mammalian cone terminals remains equivocal. Here, we looked specifically for functional GABA receptors in mouse photoreceptors by recording in the whole-cell or amphotericin/gramicidin-perforated patch clamp configurations. Cones could be differentiated from rods through morphological criteria. Local GABA applications evoked a Cl- current in cones but not in rods. It was blocked by the GABAA receptor antagonist bicuculline methiodide and unaffected by the GABAC receptor antagonist TPMPA [(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid]. The voltage dependency of the current amplitude was as expected from a direct action of GABA on cone pedicles but not from an indirect modulation of cone currents following the activation of the GABA receptors of HCs. This supports a direct role of GABA released from HCs in the control of cone activity in the mouse retina.

Preserving of vision is the main goal in vision research. The presented research evaluates the preservation of visual function in Royal College of Surgeon (RCS) rats using a depth perception test. Rats were placed on a stage with one side containing an illusory steep drop ("cliff") and another side with a minimal drop ("table"). Latency of stage dismounting and the percentage of rats that set their first foot on the "cliff" side were determined. Nondystrophic Long-Evans (LE) rats were tested as control. Electroretinogram and histology analysis were used to determine retinal function and structure. Four-week-old RCS rats presented a significantly shorter mean latency to dismount the stage compared with 6-week-old rats (mean ± standard error, 13.7 ± 1.68 vs. 20.85 ± 6.5 s, P = 0.018). Longer latencies were recorded as rats aged, reaching 45.72 s in 15-week-old rats (P < 0.00001 compared with 4-week-old rats). All rats at the age of 4 weeks placed their first foot on the table side. By contrast, at the age of 8 weeks, 28.6% rats dismounted on the cliff side and at the age of 10 and 15 weeks, rats randomly dismounted the stage to either table or cliff side. LE rats dismounted the stage faster than 4-week-old RCS rats, but the difference was not statistically significant (7 ± 1.58 s, P = 0.057) and all LE rats dismounted on the table side. The latency to dismount the stage in RCS rats correlated with maximal electroretinogram b-wave under dark and light adaptation (Spearman's rho test = -0.603 and -0.534, respectively, all P < 0.0001), outer nuclear layer thickness (Spearman's rho test = -0.764, P = 0.002), and number of S- and M-cones (Spearman's rho test = -0.763 [P = 0.002], and -0.733 [P = 0.004], respectively). The cliff avoidance test is an objective, quick, and readily available method for the determination of RCS rats' visual function.

Inhibition shapes activity and signal processing in neural networks through numerous mechanisms mediated by many different cell types. Here, we examined how one type of GABAergic interneuron in the retina, the A17 amacrine cell, influences visual information processing. Our results suggest that A17s, which make reciprocal feedback inhibitory synapses onto rod bipolar cell (RBC) synaptic terminals, extend the luminance range over which RBC synapses compute temporal contrast and enhance the reliability of contrast signals over this range. Inhibition from other amacrine cells does not influence these computational features. Although A17-mediated feedback is mediated by both GABAA and GABAC receptors, the latter plays the primary role in extending the range of contrast computation. These results identify specific functions for an inhibitory interneuron subtype, as well as specific synaptic receptors, in a behaviorally relevant neural computation.

Contrast sensitivity functions reveal information about a subject's overall visual ability and have been investigated in several species of nonhuman primates (NHPs) with experimentally induced amblyopia and glaucoma. However, there are no published studies comparing contrast sensitivity functions across these species of normal NHPs. The purpose of this investigation was to compare contrast sensitivity across these primates to determine whether they are similar. Ten normal humans and eight normal NHPs (Macaca fascicularis) took part in this project. Previously published data from Macaca mulatta and Macaca nemestrina were also compared. Threshold was operationally defined as two misses in a row for a descending method of limits. A similar paradigm was used for the humans except that the descending method of limits was combined with a spatial, two-alternative forced choice (2-AFC) technique. The contrast sensitivity functions were fit with a double exponential function. The averaged peak contrast sensitivity, peak spatial frequency, acuity, and area under the curve for the humans were 268.9, 3.40 cpd, 27.3 cpd, and 2345.4 and for the Macaca fascicularis were 99.2, 3.93 cpd, 26.1 cpd, and 980.9. A two-sample t-test indicated that the peak contrast sensitivities (P = 0.001) and areas under the curve (P = 0.010) were significantly different. The peak spatial frequencies (P = 0.150) and the extrapolated visual acuities (P = 0.763) were not different. The contrast sensitivities for the Macaca fascicularis, Macaca mulatta, and Macaca nemestrina were qualitatively and quantitatively similar. The contrast sensitivity functions for the NHPs had lower peak contrast sensitivities and areas under the curve than the humans. Even though different methods have been used to measure contrast sensitivity in different species of NHP, the functions are similar. The contrast sensitivity differences and similarities between humans and NHPs need to be considered when using NHPs to study human disease.

There are more than 30 distinct types of mammalian retinal ganglion cells, each sensitive to different features of the visual environment. In rabbit retina, they can be grouped into four classes according to their morphology and stratification of their dendrites in the inner plexiform layer (IPL). The goal of this study was to describe the synaptic inputs to one type of Class IV ganglion cell, the third member of the sparsely branched Class IV cells (SB3). One cell of this type was partially reconstructed in a retinal connectome developed using automated transmission electron microscopy (ATEM). It had slender, relatively straight dendrites that ramify in the sublamina a of the IPL. The dendrites of the SB3 cell were always postsynaptic in the IPL, supporting its identity as a ganglion cell. It received 29% of its input from bipolar cells, a value in the middle of the range for rabbit retinal ganglion cells studied previously. The SB3 cell typically received only one synapse per bipolar cell from multiple types of presumed OFF bipolar cells; reciprocal synapses from amacrine cells at the dyad synapses were infrequent. In a few instances, the bipolar cells presynaptic to the SB3 ganglion cell also provided input to an amacrine cell presynaptic to the ganglion cell. There was apparently no crossover inhibition from narrow-field ON amacrine cells. Most of the amacrine cell inputs were from axons and dendrites of GABAergic amacrine cells, likely providing inhibitory input from outside the classical receptive field.

Variability in the electrophysiological properties of homotypic photoreceptors is widespread and is thought to facilitate functioning under disparate illumination conditions. Compound eyes of insects have three sources of variability: inter-individual, intra-individual, and intra-ommatidial, the latter two overlapping. Here, I explored the causes of variability in Periplaneta americana, a nocturnal insect characterized by highly variable photoreceptor responses. By recording from photoreceptors in dissociated ommatidia, including consecutive recordings from photoreceptors in the same ommatidium (SO), I studied the variability of six properties: whole-cell membrane capacitance (Cm), phototransduction latency, maximal conductance (Gmax) and the slope factor of the sustained Kv current, absolute sensitivity in dim light, and sustained light-induced current (LIC) amplitude in bright light. Coefficient of variation (CV) metrics were used to compare variances in four experimental groups: SO, same animal (SA), all data combined "full sample" (FS), and full sample of all SO recordings (FSSO). For the normally distributed parameters Cm, Gmax, slope factor, and latency, the highest CV values were found in FS and FSSO, intermediate in SA, and the lowest in SO. On average, SO variance accounted for 47% of the full-sample variance in these four parameters. Absolute sensitivity and LIC values were not normally distributed, and the differences in variability between SO and FS/FSSO groups were smaller than for the other four parameters. These results indicate two main sources of variability, intra-ommatidial and inter-individual. Inter-individual variability was investigated by exposing adult cockroaches to constant light or dark for several months. In both groups, the majority of CV measures for the six parameters decreased compared to control, indicating substantial contribution of phenotypic plasticity to inter-individual differences. Analysis of variability of resting potential and elementary voltage responses revealed that resting potential is mainly determined by the sustained Kv conductance, whereas voltage bump amplitude is mainly determined by current bump amplitude and Cm.