Research Article
How much feedback from visual cortex to lateral geniculate nucleus in cat: A perspective
- JULIAN M.L. BUDD
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- Published online by Cambridge University Press:
- 01 July 2004, pp. 487-500
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Corticothalamic feedback is believed to play an important role in selectively regulating the flow of sensory information from thalamus to cortex. But despite its importance, the size and nature of corticothalamic pathway connectivity is not fully understood. In light of recent empirical data, the aim of this paper was to quantify the contribution of area 17 axon connectivity to the synaptic organization of A-laminae in dorsal lateral geniculate nucleus (dLGN) in cat, the best studied corticothalamic pathway. Numerical constraints indicate that most corticogeniculate synapses are not formed with inhibitory interneurons. However, the main finding is that there was an order of magnitude difference between estimates of the mean number of cortical synapses per A-laminae neuron based on individual corticogeniculate axon data (12,000–16,000 cortical synapses per cell) than that previously derived from partial reconstructions of the synaptic input to two physiologically identified relay cells (1200–1500 cortical synapses per cell). In an attempt to reconcile these different estimates, parameter variation and comparative analyses suggest that previous work may have overestimated the density of corticogeniculate efferent neurons and underestimated the total number of synapses per geniculate neuron. But as this analysis did not include area 18 corticogeniculate axons innervating A-laminae, the discrepancy between different estimates may be greater and require further explanation. Thus, the analysis presented here suggests geniculate neurons receive on average a greater number of cortical synapses per cell but from far fewer corticogeniculate axons than previously thought.
Cobalt ions inhibit negative feedback in the outer retina by blocking hemichannels on horizontal cells
- I. FAHRENFORT, T. SJOERDSMA, H. RIPPS, M. KAMERMANS
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- 01 July 2004, pp. 501-511
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In goldfish, negative feedback from horizontal cells to cones shifts the activation function of the Ca2+ current of the cones to more negative potentials. This shift increases the amount of Ca2+ flowing into the cones, resulting in an increase in glutamate release. The increased glutamate release forms the basis of the feedback-mediated responses in second-order neurons, such as the surround-induced responses of bipolar cells and the spectral coding of horizontal cells. Low concentrations of Co2+ block these feedback-mediated responses in turtle retina. The mechanism by which this is accomplished is unknown. We studied the effects of Co2+ on the cone/horizontal network of goldfish retina and found that Co2+ greatly reduced the feedback-mediated responses in both cones and horizontal cells in a GABA-independent way. The reduction of the feedback-mediated responses is accompanied by a small shift of the Ca2+ current of the cones to positive potentials. We have previously shown that hemichannels on the tips of the horizontal cell dendrites are involved in the modulation of the Ca2+ current in cones. Both the absence of this Co2+-induced shift of the Ca2+ current in the absence of a hemichannel conductance and the sensitivity of Cx26 hemichannels to low concentrations of Co2+ are consistent with a role for hemichannels in negative feedback from horizontal cells to cones.
Visual sensitivity across the menstrual cycle
- ALVIN EISNER, SARA N. BURKE, MAUREEN D. TOOMEY
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- 01 July 2004, pp. 513-531
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This study was designed to evaluate the hypothesis that hormonal change can affect lower level light-adaptation processes, which are likely to be retinally based. Foveal visual sensitivities were measured across several menstrual cycles of four women not using hormonally acting medication and across several menstrual cycles of three women using a triphasic oral contraceptive. One woman, diagnosed with premenstrual syndrome (PMS), was a subject for both groups. Sensitivities were measured for a series of test wavelengths for 580-nm backgrounds of 2.0 and 4.0 log td. Of the six individuals tested, one had clear evidence of visual-adaptation changes occurring in phase with the menstrual cycle. Prior to using the oral contraceptive, this individual (the PMS subject) experienced changes of short-wavelength-sensitive (SWS)-cone-mediated sensitivities of up to about 1.4 log unit on the 4.0 log td background. Her SWS-cone-mediated sensitivities tended to be highest near ovulation and lowest premenstrually. Threshold-versus-illuminance (TVI) curves confirmed that the rate of sensitivity decrease with increasing background illuminance (i.e. the TVI slope) was greater premenstrually. The degree of background-induced desensitization within her middle-wavelength-sensitive (MWS)/long-wavelength-sensitive (LWS) cone pathways also appeared to vary cyclically, but the magnitude of the variation was smaller and the time course appeared to be different. When this subject began oral contraceptive use, the patterns of sensitivity change were all altered. None of the other five subjects experienced changes of SWS-cone-mediated vision that were cyclic and significantly adaptation-state dependent. However, there was evidence for a limited degree of cyclic adaptation change within the MWS/LWS cone pathways of at least one additional subject. We conclude that hormonal change can—for some unknown proportion of women—be linked to alterations of retinal function. However, the alterations are not the same for all visual pathways, and there are pronounced individual differences. The data also demonstrate that individuals' visual adaptation capabilities can vary substantially over periods of weeks.
Origins of the electroretinogram oscillatory potentials in the rabbit retina
- CUN-JIAN DONG, PETER AGEY, WILLIAM A. HARE
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- 01 July 2004, pp. 533-543
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The electroretinogram (ERG) oscillatory potential (OP) is a high-frequency, low-amplitude potential that is superimposed on the rising phase of the b-wave. It provides noninvasive evaluation of inner retina function in vivo and is a useful tool in basic research as well as in the clinic. While the OP is widely believed to be generated mainly by activity of the inner retina, the exact underlying neural mechanisms are not well understood. We have investigated the retinal mechanisms that underlie OP generation in Dutch-belted rabbits. The OP was isolated by band-filtering (100–1000 Hz) ERG signals. We used pharmacological agents that block specific transmitter receptors or voltage-gated channels in order to examine contributions of various retinal mechanisms to OP generation. Our results show that the OP elicited by a bright brief flash can be classified into early, intermediate, and late subgroups that are likely generated mainly by photoreceptors, action-potential-independent, and action-potential-dependent mechanisms in the ON pathway of the inner retina, respectively. ON bipolar cells themselves make only a small direct contribution to OP generation, as do horizontal cells and neurons in the OFF pathway.
N-type and L-type calcium channels mediate glycinergic synaptic inputs to retinal ganglion cells of tiger salamanders
- MARK C. BIEDA, DAVID R. COPENHAGEN
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- 01 July 2004, pp. 545-550
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Synaptically localized calcium channels shape the timecourse of synaptic release, are a prominent site for neuromodulation, and have been implicated in genetic disease. In retina, it is well established that L-type calcium channels play a major role in mediating release of glutamate from the photoreceptors and bipolar cells. However, little is known about which calcium channels are coupled to synaptic exocytosis of glycine, which is primarily released by amacrine cells. A recent report indicates that glycine release from spiking AII amacrine cells relies exclusively upon L-type calcium channels. To identify calcium channel types controlling neurotransmitter release from the population of glycinergic neurons that drive retinal ganglion cells, we recorded electrical and potassium evoked inhibitory synaptic currents (IPSCs) from these postsynaptic neurons in retinal slices from tiger salamanders. The L-channel antagonist nifedipine strongly inhibited release and FPL64176, an L-channel agonist, greatly enhanced it, indicating a significant role for L-channels. ω-Conotoxin MVIIC, an N/P/Q-channel antagonist, strongly inhibited release, indicating an important role for non-L channels. While the P/Q-channel blocker ω-Aga IVA produced only small effects, the N-channel blocker ω-conotoxin GVIA strongly inhibited release. Hence, N-type and L-type calcium channels appear to play major roles, overall, in mediating synaptic release of glycine onto retinal ganglion cells.
Differential cellular and subcellular distribution of glutamate transporters in the cat retina
- BOZENA FYK-KOLODZIEJ, PU QIN, ARTURIK DZHAGARYAN, ROBERTA G. POURCHO
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- 01 July 2004, pp. 551-565
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Retrieval of glutamate from extracellular sites in the retina involves at least five excitatory amino acid transporters. Immunocytochemical analysis of the cat retina indicates that each of these transporters exhibits a selective distribution which may reflect its specific function. The uptake of glutamate into Müller cells or astrocytes appears to depend upon GLAST and EAAT4, respectively. Staining for EAAT4 was also seen in the pigment epithelium. The remaining transporters are neuronal with GLT-1α localized to a number of cone bipolar, amacrine, and ganglion cells and GLT-1v in cone photoreceptors and several populations of bipolar cells. The EAAC1 transporter was found in horizontal, amacrine, and ganglion cells. Staining for EAAT5 was seen in the axon terminals of both rod and cone photoreceptors as well as in numerous amacrine and ganglion cells. Although some of the glutamate transporter molecules are positioned for presynaptic or postsynaptic uptake at glutamatergic synapses, others with localizations more distant from such contacts may serve in modulatory roles or provide protection against excitoxic or oxidative damage.
The computational basis of an identified neuronal circuit for elementary motion detection in dipterous insects
- CHARLES M. HIGGINS, JOHN K. DOUGLASS, NICHOLAS J. STRAUSFELD
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- 01 July 2004, pp. 567-586
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Based on comparative anatomical studies and electrophysiological experiments, we have identified a conserved subset of neurons in the lamina, medulla, and lobula of dipterous insects that are involved in retinotopic visual motion direction selectivity. Working from the photoreceptors inward, this neuronal subset includes lamina amacrine (α) cells, lamina monopolar (L2) cells, the basket T-cell (T1 or β), the transmedullary cell Tm1, and the T5 bushy T-cell. Two GABA-immunoreactive neurons, the transmedullary cell Tm9 and a local interneuron at the level of T5 dendrites, are also implicated in the motion computation. We suggest that these neurons comprise the small-field elementary motion detector circuits the outputs of which are integrated by wide-field lobula plate tangential cells. We show that a computational model based on the available data about these neurons is consistent with existing models of biological elementary motion detection, and present a comparable version of the Hassenstein-Reichardt (HR) correlation model. Further, by using the model to synthesize a generic tangential cell, we show that it can account for the responses of lobula plate tangential cells to a wide range of transient stimuli, including responses which cannot be predicted using the HR model. This computational model of elementary motion detection is the first which derives specifically from the functional organization of a subset of retinotopic neurons supplying the lobula plate. A key prediction of this model is that elementary motion detector circuits respond quite differently to small-field transient stimulation than do spatially integrated motion processing neurons as observed in the lobula plate. In addition, this model suggests that the retinotopic motion information provided to wide-field motion-sensitive cells in the lobula is derived from a less refined stage of processing than motion inputs to the lobula plate.
Localization of NMDA receptor subunits and mapping NMDA drive within the mammalian retina
- MICHAEL KALLONIATIS, DANIEL SUN, LISA FOSTER, SILKE HAVERKAMP, HEINZ WÄSSLE
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- 01 July 2004, pp. 587-597
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Glutamate is a major neurotransmitter in the retina and other parts of the central nervous system, exerting its influence through ionotropic and metabotropic receptors. One ionotropic receptor, the N-methyl-D-aspartate (NMDA) receptor, is central to neural shaping, but also plays a major role during neuronal development and in disease processes. We studied the distribution pattern of different subunits of the NMDA receptor within the rat retina including quantifying the pattern of labelling for all the NR1 splice variants, the NR2A and NR2B subunits. The labelling pattern for the subunits was confined predominantly in the outer two-thirds of the inner plexiform layer. We also wanted to probe NMDA receptor function using an organic cation, agmatine (AGB); a marker for cation channel activity. Although there was an NMDA concentration-dependent increase in AGB labelling of amacrine cells and ganglion cells, we found no evidence of functional NMDA receptors on horizontal cells in the peripheral rabbit retina, nor in the visual streak where the type A horizontal cell was identified by GABA labelling. Basal AGB labelling within depolarizing bipolar cells was also noted. This basal bipolar cell AGB labelling was not modulated by NMDA and was completely abolished by the use of L-2-amino-4-phosphono-butyric acid, which is known to hyperpolarize retinal depolarizing bipolar cells. AGB is therefore not only useful as a probe of ligand-gated drive, but can also identify neurons that have constitutively open cationic channels. In combination, the NMDA receptor subunit distribution pattern and the AGB gating experiments strongly suggests that this ionotropic glutamate receptor is functional in the cone-driven pathway of the inner retina.
Light-induced Ca2+ release in the visible cones of the zebrafish
- MARIANNE C. CILLUFFO, HUGH R. MATTHEWS, SUSAN E. BROCKERHOFF, GORDON L. FAIN
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- 01 July 2004, pp. 599-609
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We used suction-pipette recording and fluo-4 fluorescence to study light-induced Ca2+ release from the visible double cones of zebrafish. In Ringer, light produces a slow decrease in fluorescence which can be fitted by the sum of two decaying exponentials with time constants of 0.5 and 3.8 s. In 0Ca2+–0Na+ solution, for which fluxes of Ca2+ across the outer segment plasma membrane are greatly reduced, light produces a slow increase in fluorescence. Both the decrease and increase are delayed after incorporation of the Ca2+ chelator BAPTA, indicating that both are produced by a change in Ca2+. If the Ca2+ pool is first released by bright light in 0Ca2+–0Na+ solution and the cone returned to Ringer, the time course of Ca2+ decline is much faster than in Ringer without previous light exposure. This indicates that the time constants of 0.5 and 3.8 s actually reflect a sum of Na+/Ca2+-K+ exchange and light-induced release of Ca2+. The Ca2+ released by light appears to come from at least two sites, the first comprising 66% of the total pool and half-released by bleaching 4.8% of the pigment. Release of the remaining Ca2+ from the second site requires the bleaching of nearly all of the pigment. If, after release, the cone is maintained in darkness, a substantial fraction of the Ca2+ returns to the release pool even in the absence of pigment regeneration. The light-induced release of Ca2+ can produce a modulation of the dark current as large as 0.75 pA independently of the normal transduction cascade, though the rise time of the current is considerably slower than the normal light response. These experiments show that Ca2+ can be released within the cone outer segment by light intensities within the physiological range of photopic vision. The role this Ca2+ release plays remains unresolved.
Direction selectivity in a model of the starburst amacrine cell
- JOHN J. TUKKER, W. ROWLAND TAYLOR, ROBERT G. SMITH
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- 01 July 2004, pp. 611-625
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The starburst amacrine cell (SBAC), found in all mammalian retinas, is thought to provide the directional inhibitory input recorded in On–Off direction-selective ganglion cells (DSGCs). While voltage recordings from the somas of SBACs have not shown robust direction selectivity (DS), the dendritic tips of these cells display direction-selective calcium signals, even when γ-aminobutyric acid (GABAa,c) channels are blocked, implying that inhibition is not necessary to generate DS. This suggested that the distinctive morphology of the SBAC could generate a DS signal at the dendritic tips, where most of its synaptic output is located. To explore this possibility, we constructed a compartmental model incorporating realistic morphological structure, passive membrane properties, and excitatory inputs. We found robust DS at the dendritic tips but not at the soma. Two-spot apparent motion and annulus radial motion produced weak DS, but thin bars produced robust DS. For these stimuli, DS was caused by the interaction of a local synaptic input signal with a temporally delayed “global” signal, that is, an excitatory postsynaptic potential (EPSP) that spread from the activated inputs into the soma and throughout the dendritic tree. In the preferred direction the signals in the dendritic tips coincided, allowing summation, whereas in the null direction the local signal preceded the global signal, preventing summation. Sine-wave grating stimuli produced the greatest amount of DS, especially at high velocities and low spatial frequencies. The sine-wave DS responses could be accounted for by a simple mathematical model, which summed phase-shifted signals from soma and dendritic tip. By testing different artificial morphologies, we discovered DS was relatively independent of the morphological details, but depended on having a sufficient number of inputs at the distal tips and a limited electrotonic isolation. Adding voltage-gated calcium channels to the model showed that their threshold effect can amplify DS in the intracellular calcium signal.
Spatial, temporal, and intensive determinants of dopamine release in the chick retina
- W.A. LUFT, P.M. IUVONE, W.K. STELL
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- 01 July 2004, pp. 627-635
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The retinal dopaminergic system is a global regulator of retinal function. Apart from the fact that the rates of dopamine synthesis and release are increased by increasing illumination, the visual image parameters that influence dopaminergic function are mostly unknown. Roles for spatial and temporal frequency and image contrast are suggested by the effects of form-deprivation with a diffusing goggle. Form-deprivation reduces the rates of dopamine synthesis and release, and induces myopia, which is prevented by dopamine agonists. Our purpose here was to identify visual stimulus parameters that activate dopaminergic amacrine cells and elicit dopamine release. White Leghorn cockerels 4–7 days old were exposed to 2 h of form-deprivation, reduced light intensity, or stimuli of varied temporal or spatial frequency. Activation of dopaminergic neurons, labeled for tyrosine hydroxylase (TH), was assessed with immunocytochemistry for c-Fos, and dopamine release was measured by HPLC analysis of dopamine metabolite accumulation in the vitreous body. Form-deprivation did not reduce TH+ cell activation or vitreal dopamine metabolite accumulation any more than did neutral-density filters of approximately equal transmittance. TH+ cell activation and vitreal metabolite accumulation were not affected significantly by exposure to 2, 5, 10, 15, or 20 Hz stroboscopic stimulation on a dark background, or by sine-wave gratings of 0.089, 0.44, 0.89, 1.04, or 3.13 cycles/deg compared to a uniform gray target of equal mean luminance. These data indicate that the retinal dopaminergic system does not respond readily to short-term changes in visual stimulus parameters, other than light intensity, under the conditions of these experiments.
Retinal glucose metabolism in mice lacking the L-glutamate/aspartate transporter
- VIJAY P. SARTHY, V. JOSEPH DUDLEY, KOHICHI TANAKA
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- 01 July 2004, pp. 637-643
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The conventional view that glucose is the substrate for neuronal energy metabolism has been recently challenged by the “lactate shuttle” hypothesis in which glutamate cycling in glial cells drives all neuronal glucose metabolism. According to this view, glutamate released by activated retinal neurons is transported into Müller (glial) cells where it triggers glycolysis. The lactate released by Müller cells serves as the energy substrate for neuronal metabolism. Because the L-Glutamate/aspartate transporter (GLAST) is the predominant, Na+-dependent, glutamate transporter expressed by Müller cells, we have used GLAST-knockout (GLAST−/−) mice to examine the relationship between lactate release and GLAST activity in the retina. We found that glucose uptake and lactate production by the GLAST−/− mouse retina was similar to that observed in the wild type mouse retina. Furthermore, addition of 1 mM glutamate and NH4Cl to the incubation medium did not further stimulate glucose uptake in either case. When lactate release was measured in the presence of the lactate uptake inhibitor, α-cyano-4-hydroxycinnamate, there was no significant change in the amount of lactate released by retinas from GLAST−/− mice compared to the wild type. Finally, lactate release was similar under both dark and light conditions. These results show that lactate production and release is not altered in retinas of GLAST−/− mice, which suggests that metabolic coupling between photoreceptors and Müller cells is not mediated by the glial glutamate transporter, GLAST.
Characterization of inhibitory postsynaptic currents in rod bipolar cells of the mouse retina
- MORITZ J. FRECH, KURT H. BACKUS
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- 01 July 2004, pp. 645-652
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The synaptic terminals of mammalian rod bipolar cells are the targets of multiple presynaptic inhibitory inputs arriving from glycinergic and GABAergic amacrine cells. To investigate the contribution of these different inhibitory receptor types, we have applied the patch-clamp technique in acutely isolated slices of the adult mouse retina. By using the whole-cell configuration, we measured and analyzed the spontaneous postsynaptic currents (PSCs) in rod bipolar cells. The spontaneous synaptic activity of rod bipolar cells was very low. However, when amacrine cells were depolarized by AMPA or kainate, the PSC frequency in rod bipolar cells increased significantly. These PSCs comprised several types that could be distinguished by pharmacological and kinetic criteria. Strychnine-sensitive, glycinergic PSCs were characterized by a mean peak amplitude of −43.5 pA and a weighted decay time constant (τw) of 10.9 ms. PSCs that persisted in the presence of strychnine, but were completely inhibited by bicuculline, were mediated by GABAARs. They had a mean peak amplitude of −20.0 pA and a significantly faster τw of 5.8 ms. Few PSCs remained in the presence of strychnine and bicuculline, suggesting that they were mediated by GABACRs. These PSCs were characterized by much smaller amplitudes (−6.2 pA) and a significantly slower decay kinetics (τw = 51.0 ms). We conclude that rod bipolar cells express at least three types of functionally different inhibitory receptors, namely GABAARs, GABACRs, and GlyRs that may ultimately regulate the Ca2+ influx into rod bipolar cell terminals, thereby modulating their glutamate release.
Experience-dependent changes in NMDAR1 expression in the visual cortex of an animal model for amblyopia
- KATHRYN M. MURPHY, KEVIN R. DUFFY, DAVID G. JONES
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- 01 July 2004, pp. 653-670
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When normal binocular visual experience is disrupted during postnatal development, it affects the maturation of cortical circuits and often results in the development of poor visual acuity known as amblyopia. Two main factors contribute to the development of amblyopia: visual deprivation and reduced binocular competition. We investigated the affect of these two amblyogenic factors on the expression of the NMDAR1 subunit in the visual cortex because activation of the NMDA receptor is a key mechanism of developmental neural plasticity. We found that disruption of binocular correlations by monocular deprivation promoted a topographic loss of NMDAR1 expression within the cortical representations of the central visual field and the vertical and horizontal meridians. In contrast, binocular deprivation, which primarily affects visual deprivation, promoted an increase in NMDAR1 expression throughout the visual cortex. These different changes in NMDAR1 expression can be described as topographic and homeostatic plasticity of NMDA expression, respectively. In addition, the changes in NMDA expression in the visual cortex provide a greater understanding of the neural mechanisms that underlie the development of amblyopia and the potential for visual recovery.