Visual Neuroscience最新文献

Comparative studies have greatly contributed to our understanding of the organization and function of visual pathways of the brain, including that of humans. This comparative approach is a particularly useful tactic for studying the pulvinar nucleus, an enigmatic structure which comprises the largest territory of the human thalamus. This review focuses on the regions of the mouse pulvinar that receive input from the superior colliculus, and highlights similarities of the tectorecipient pulvinar identified across species. Open questions are discussed, as well as the potential contributions of the mouse model for endeavors to elucidate the function of the pulvinar nucleus.

Chronic low grade inflammation is considered to contribute to the development of experimental diabetic retinopathy (DR). We recently demonstrated that lack of CD40 in mice ameliorates the upregulation of inflammatory molecules in the diabetic retina and prevented capillary degeneration, a hallmark of experimental diabetic retinopathy. Herein, we investigated the contribution of CD40 to diabetes-induced reductions in retinal function via the electroretinogram (ERG) to determine if inflammation plays a role in the development of ERG defects associated with diabetes. We demonstrate that diabetic CD40-/- mice are not protected from reduction to the ERG b-wave despite failing to upregulate inflammatory molecules in the retina. Our data therefore supports the hypothesis that retinal dysfunction found in diabetics occurs independent of the induction of inflammatory processes.

Vertebrate rod and cone photoreceptors require continuous supply of chromophore for regenerating their visual pigments after photoactivation. Cones, which mediate our daytime vision, demand a particularly rapid supply of 11-cis retinal chromophore in order to maintain their function in bright light. An important contribution to this process is thought to be the chromophore precursor 11-cis retinol, which is supplied to cones from Müller cells in the retina and subsequently oxidized to 11-cis retinal as part of the retina visual cycle. However, the molecular identity of the cis retinol oxidase in cones remains unclear. Here, as a first step in characterizing this enzymatic reaction, we sought to determine the subcellular localization of this activity in salamander red cones. We found that the onset of dark adaptation of isolated salamander red cones was substantially faster when exposing directly their outer vs. their inner segment to 9-cis retinol, an analogue of 11-cis retinol. In contrast, this difference was not observed when treating the outer vs. inner segment with 9-cis retinal, a chromophore analogue which can directly support pigment regeneration. These results suggest, surprisingly, that the cis-retinol oxidation occurs in the outer segments of cone photoreceptors. Confirming this notion, pigment regeneration with exogenously added 9-cis retinol was directly observed in the truncated outer segments of cones, but not in rods. We conclude that the enzymatic machinery required for the oxidation of recycled cis retinol as part of the retina visual cycle is present in the outer segments of cones.

Adenosine is a neuromodulator present in various areas of the central nervous system, including the retina. Adenosine may serve a neuroprotective role in the retina, based on electroretinogram (ERG) recordings from the rat retina. Our purpose was to assess the role of A2A and A3 adenosine receptors in the generation and modulation of the rat ERG. The flash ERG was recorded with corneal electrodes from Sprague Dawley rats. Agonists and antagonists for A2A and A3 receptors, and adenosine were injected (5 µl) into the vitreous. The effects on the components of the single flash scotopic and photopic ERGs were examined, and ERG flicker. Adenosine (0.5 mM) increased the mean amplitudes of the scotopic ERG a-waves (68 ± 8 to 97 ± 14 µV, P = 0.042), and b-waves (236 ± 38 µV to 305 ± 42 µV). A2A agonist CGS21680 (2 mM) reduced the mean amplitude of the ERG b-wave, from 298 ± 21 µV in response to the brightest stimulus to 212 ± 19 µV (P = 0.005), and mean scotopic oscillatory potentials (OPs) from 100 ± 9 µV to 47 ± 11 µV (P = 0.023). ZM241385 [4 mM], an A2A antagonist, decreased the scotopic b-wave of the ERG. A3 agonist 2-CI-IB-MECA (0.5 mM) increased the a-wave, while decreasing the scotopic and photopic ERG b-waves, and the scotopic OPs. A3 antagonist VUF5574 (1 mM) increased the mean amplitude of the scotopic a-wave (66 ± 8 to 140 ± 29 µV, P = 0.046) and b-wave (224 ± 20 to 312 ± 39 µV, P = 0.0037). No significant effects on ERG flicker were found. We conclude that retinal neurons containing A2A and/or A3 adenosine receptors contribute to the generation of the ERG a- and b-waves and OPs.

Rod-cone gap junctions mediate the so-called "secondary rod pathway", one of three routes that convey rod photoreceptor signals across the retina. Connexin 36 (Cx36) is expressed at these gap junctions, but an unidentified connexin protein also seems to be expressed. Cx36 knockout mice have been used extensively in the quest to dissect the roles in vision of all three pathways, with the assumption, never directly tested, that rod-cone electrical coupling is abolished by deletion of this connexin isoform. We previously showed that when wild type mouse cones couple to rods, their apparent dynamic range is extended toward lower light intensities, with the appearance of large responses to dim flashes (up to several mV) originating in rods. Here we recorded from the cones of Cx36del[LacZ]/del[LacZ] mice and found that dim flashes of the same intensity evoked at most small sub-millivolt responses. Moreover, these residual responses originated in the cones themselves, since: (i) their spectral preference matched that of the recorded cone and not of rods, (ii) their time-to-peak was shorter than in coupled wild type cones, (iii) a pharmacological block of gap junctions did not reduce their amplitude. Taken together, our data show that rod signals are indeed absent in the cones of Cx36 knockout mice. This study is the first direct demonstration that Cx36 is crucial for the assembly of functional rod-cone gap junctional channels, implying that its genetic deletion is a reliable experimental approach to eliminate rod-cone coupling.

Often mislabeled as a simple relay of sensory information, the thalamus is a complicated structure with diverse functions. This diversity is exemplified by roles visual thalamus plays in processing and transmitting light-derived stimuli. Such light-derived signals are transmitted to the thalamus by retinal ganglion cells (RGCs), the sole projection neurons of the retina. Axons from RGCs innervate more than ten distinct nuclei within thalamus, including those of the lateral geniculate complex. Nuclei within the lateral geniculate complex of nocturnal rodents, which include the dorsal lateral geniculate nucleus (dLGN), ventral lateral geniculate nucleus (vLGN), and intergeniculate leaflet (IGL), are each densely innervated by retinal projections, yet, exhibit distinct cytoarchitecture and connectivity. These features suggest that each nucleus within this complex plays a unique role in processing and transmitting light-derived signals. Here, we review the diverse cytoarchitecture and connectivity of these nuclei in nocturnal rodents, in an effort to highlight roles for dLGN in vision and for vLGN and IGL in visuomotor, vestibular, ocular, and circadian function.

Previous psychophysical evidence suggests that motion and orientation processing systems interact asymmetrically in the human visual system, with orientation information having a stronger influence on the perceived motion direction than vice versa. To investigate the mechanisms underlying this motion-form interaction we used moving and oriented Glass patterns (GPs), which consist of randomly distributed dot pairs (dipoles) that induce the percept of an oriented texture. In Experiment 1 we varied the angle between dipole orientation and motion direction (conflict angle). In separate sessions participants either judged the orientation or motion direction of the GP. In addition, the spatiotemporal characteristics of dipole motion were manipulated as a way to limit (Experiment 1) or favor (Experiment 2) the availability of orientation signals from motion (motion streaks). The results of Experiment 1 showed that apparent GP motion direction is attracted toward dipole orientation, and apparent GP orientation is repulsed from GP motion. The results of Experiment 2 showed stronger repulsion effects when judging the GP orientation, but stronger motion streaks from the GP motion can dominate over the signals provided by conflicting dipole orientation. These results are consistent with the proposal that two separate mechanisms contribute to our perception of stimuli which contain conflicting orientation and motion information: (i) perceived GP motion is mediated by spatial motion-direction sensors, in which signals from motion sensors are combined with excitatory input from orientation-tuned sensors tuned to orientations parallel to the axis of GP motion, (ii) perceived GP orientation is mediated by orientation-tuned sensors which mutually inhibit each other. The two mechanisms are revealed by the different effects of conflict angle and dipole lifetime on perceived orientation and motion direction.

The contribution of the purinergic receptors P2X7 (P2X7Rs) to the electroretinographic (ERG) responses was studied by testing the effects of the selective P2X7R antagonist A438079 and the selective P2X7R agonist Bz-ATP on the electroretinograms obtained in perfused frog (Rana ridibunda) eyecup preparations under a variety of stimulation conditions. The P2X7R blockade by 200 µM A438079 diminished the amplitude of the photoreceptor components: the a-wave and the pharmacologically isolated mass receptor potential. In the pure rod-driven and pure cone-driven responses, the amplitude of the postreceptoral ON (b-wave) and OFF (d-wave) components was also diminished. The OFF responses were affected to a greater extent compared to the ON responses. In the mixed rod- and cone-driven responses, obtained in the mesopic intensity range, the b-wave amplitude was increased, while the d-wave amplitude was decreased. The amplitude of the oscillatory potentials was diminished. The relative amplitude changes produced by the P2X7R blockade were greater in the dark-adapted compared to the light-adapted eyes. The application of 100 µM Bz-ATP produced small effects opposite to those of the antagonist, while a prolonged (>20 min) treatment with 1 mM Bz-ATP resulted in a significant amplitude reduction or even abolishment of b- and d-waves. Our results show that endogenous ATP through its P2X7Rs exerts significant, mostly potentiating effects on the ERG photoreceptor and postreceptoral responses. There is a clear ON/OFF asymmetry of the effects on the ERG postreceptoral responses favoring OFF responses: they are always strongly potentiated, while the ON responses are either less potentiated (in the rod-driven and most of the cone-driven responses) or even inhibited (in the mixed rod- and cone-driven responses). The overstimulation of P2X7Rs can produce acute pathological changes, that is, a decrease or abolishment of the ERG responses.

We examined the effect of intravitreal injections of D1-like and D2-like dopamine receptor agonists and antagonists and D4 receptor drugs on form-deprivation myopia (FDM) in tree shrews, mammals closely related to primates. In eleven groups (n = 7 per group), we measured the amount of FDM produced by monocular form deprivation (FD) over an 11-day treatment period. The untreated fellow eye served as a control. Animals also received daily 5 µL intravitreal injections in the FD eye. The reference group received 0.85% NaCl vehicle. Four groups received a higher, or lower, dose of a D1-like receptor agonist (SKF38393) or antagonist (SCH23390). Four groups received a higher, or lower, dose of a D2-like receptor agonist (quinpirole) or antagonist (spiperone). Two groups received the D4 receptor agonist (PD168077) or antagonist (PD168568). Refractions were measured daily; axial component dimensions were measured on day 1 (before treatment) and day 12. We found that in groups receiving the D1-like receptor agonist or antagonist, the development of FDM and altered ocular component dimensions did not differ from the NaCl group. Groups receiving the D2-like receptor agonist or antagonist at the higher dose developed significantly less FDM and had shorter vitreous chambers than the NaCl group. The D4 receptor agonist, but not the antagonist, was nearly as effective as the D2-like agonist in reducing FDM. Thus, using intravitreally-administered agents, we did not find evidence supporting a role for the D1-like receptor pathway in reducing FDM in tree shrews. The reduction of FDM by the dopamine D2-like agonist supported a role for the D2-like receptor pathway in the control of FDM. The reduction of FDM by the D4 receptor agonist, but not the D4 antagonist, suggests an important role for activation of the dopamine D4 receptor in the control of axial elongation and refractive development.