Extracellular single-unit recordings were made from simple cells in area 17 of anesthetized cats. Cells were tested with drifting gratings under control and adapted conditions. Response amplitude and phase were measured as a function of either contrast or temporal frequency. Adapting not only reduces amplitude, but also retards phase. Adaptation alters the responses of simple cells in a particular way: the onset of the response to each cycle of a sinusoidally modulated stimulus is delayed. Once cells start to respond during each cycle, however, they generally recover to control levels, and the offset of the response is unaffected by adapting. The timing aftereffects are independent of the amplitude aftereffects. Timing aftereffects are tuned around the adapting temporal frequency, with a bias toward lower temporal frequencies. Adaptation thus modifies cortical responses even more specifically then previously thought. Firing rates are depressed primarily at response onset, even after several stimulus cycles have occurred following the end of adapting. Because all cells appear to adapt in this way, the data offer an opportunity to theorize about cortical connectivity. One implication is that inhibition onto a simple cell arises from other simple cells with similar response properties that fire a half-cycle out of phase with the target cell.

The effects of dopamine on luminosity-type horizontal cells have been documented in different vertebrate retinas, both in vivo and in vitro. Some of these effects may reflect direct action of dopamine onto these cells, but indirect effects mediated by presynaptic neurons cannot be ruled out. Furthermore, direct effects of dopamine on horizontal cells may affect other, postsynaptic neurons in the outer plexiform layer. To test these possibilities, we studied the effects of dopamine on photoreceptors and all types of horizontal cells in the turtle (Pseudemys scripta elegans) retina. Receptive-field properties, responsiveness to light, and time course of light responses were monitored with intracellular recordings. Dopamine at a concentration of 40 μM exerted effects with two different time courses. “Short-term” effects were fully developed after 3 min of dopamine application and reversed within 30 min of washout of the drug. “Long-term” effects were fully developed after about 7–10 min and could not be washed out during the course of our experiments. Only the “short-term” effects were studied in detail in this paper. These were expressed in a reduction of the receptive-field size of all types of horizontal cells studied; L1 and L2 luminosity types as well as Red/Green and Yellow/Blue chromaticity types. The L1 horizontal cells did not exhibit signs of reduced responsiveness to light under dopamine, while in the L2 cells and the two types of chromaticity cells responsiveness decreased. None of the rods, long-wavelength-sensitive, or medium-wavelength-sensitive cones exhibited any apparent reduction in their receptive-field sizes or responsiveness to light. The present results suggest that the “short-term” effects of dopamine are not mediated by photoreceptors and are probably due to direct action of dopamine on horizontal cells.

The purpose of this study was to evaluate the use of slow multifocal m-sequence stimulation in analyzing the topographic distribution and underlying mechanisms (including nonlinearities) of the retinal oscillatory potentials (OPs). In giving us access to the response topography and the nonlinear characteristics of the OP,, the m-sequence technique provides us with two important means for the identification and characterization of the signal sources. In this study, we analyzed the OPs into the first- and second-order components and investigated their topographies and luminance dependence. The distribution of both the first- and second-order OP components differed significantly from that of the nicker ERG investigated by Sutter and Tran (1992). At eccentricities and luminance levels favoring activity by both rods and cones, the second-order OPs were particularly prominent showing the most clear-defined and complex waveform The topographic distribution of the second-order OPs showed combined features of both rod and cone distributions On a strong rod-bleaching background the second-order OPs were eliminated and the first-order OPs showed a reduced amplitude and a shifted latency These results are consistent with the notion that the second-order component of the OPs is dominated by contributions from rod-cone interactions.

The retinas of placental mammals appear to lack the large number and morphological diversity of cone subtypes found in diurnal reptiles. We have now studied the photoreceptor layer of a South American marsupial (Didelphis marsupialis aurita) by peanut agglutinin labeling of the cone sheath and by labeling of cone outer segments with monoclonal anti-visual pigment antibodies that have been proven to consistently label middle-to-long wavelength (COS-1) and short-wavelength (OS-2) cone subpopulations in placental mammals. Besides a dominant rod population (max. = 400,000/mm2) four subtypes of cones (max. = 3000/mm2) were identified. The outer segments of three cone subtypes were labeled by COS-1: a double cone with a principal cone containing a colorless oil droplet, a single cone with oil droplet, and another single cone. A second group of single cones lacking oil droplets was labeled by OS-2 antibody. The topography of these cone subtypes showed striking anisotropies. The COS-1 labeled single cones without oil droplets were found all over the retina and constituted the dominant population in the area centralis located in the temporal quadrant of the upper, tapetal hemisphere. The population of OS-2 labeled cones was also ubiquitous although slightly higher in the upper hemisphere (200/mm2). The COS-1 labeled cones bearing an oil droplet, including the principal member of double cones, were concentrated (800/mm2) in the inferior, non-tapetal half of the retina. The two spectral types of single cones resemble those of dichromatic photopic systems in most placental mammals. The additional set of COS-1 labeled cones is a distinct marsupial feature. The presence of oil droplets in this cone subpopulation, its absence in the area centralis, and the correlation with the non-tapetal inferior hemisphere suggest a functional specialization, possibly for mesopic conditions. Thus, sauropsid features have been retained but probably with a modified function.

The influence of postnatal neuronal activity on the magnitude of retinal ganglion cell death has been studied in cats. A constant blockade of activity in one eye starting just after birth does not change the severity of naturally occurring ganglion cell death, and as in normal animals, the ganglion cell population declines from 250,000 to 160,000 over a 4- to 6-week period. However, the population of retinal ganglion cells in the active untreated eye of monocularly deprived cats is increased 12% above normal (180,000 vs. 160,000 in each of four cases). This increase of 20,000 cells is permanent, and presumably reflects the competitive advantage in their target nuclei that the still active axons have over their silenced companions from the treated eye. Surprisingly, in one animal treated successfully for long duration with TTX in both eyes, the population of ganglion cells was elevated in both eyes (200,000 and 208,000 ganglion cells). This increase matches that achieved by early unilateral enucleation (Williams et al., 1983). Our results demonstrate that the complete blockade of activity reduces the severity of naturally occurring cell death in a population of CNS sensory neurons. The effects of unilateral blockade emphasize that the activity-dependent modulation of neuron death only occurs under conditions that do not place the inactive population of neurons at a competitive disadvantage.

Using rhodamine-labelled latex beads as a retrograde tracer, we have shown that a subset of the neurons projecting from the lateral thalamic nucleus to the optic tectum of the leopard frog are neuropeptide Y-like immunoreactive (NPY-IR). In juvenile frogs, approximately twice as many lateral thalamic nucleus cells from this area project to the ipsilateral tectum as project to the contralateral tectum. NPY-IR cells make up 25% of the projection to the ipsilateral tectum and 13% of the projection to the contralateral tectum. The ipsilateral NPY-IR projection from the lateral nucleus was present in tadpoles and was similar in its characteristics to that found in the juvenile frog. However, the contralateral tectal projection was virtually nonexistent in these animals. The results of these experiments suggest that NPY from the lateral nucleus is released into the ipsilateral tectal neuropil in both the developing and adult frog.

This paper examines how the responses of cells in area 17 of the cat vary as a function of the vernier offset between a bright and a dark bar. The study was prompted by the finding that human vernier acuity is reduced for bars or edges of opposite contrast sign (Mather & Morgan, 1986; O'Shea & Mitchell, 1990). Both simple and complex cells showed V-shaped tuning curves for reverse contrast stimuli: i.e. response was minimum at alignment, and increased with increasing vernier offset. For vernier bars with the same contrast sign, γ-shaped tuning curves were found, as reported earlier (Swindale & Cynader, 1986). Sensitivity to offset was inversely correlated in the two paradigms. However, complex cells with high sensitivity to offsets in a normal vernier stimulus were significantly less sensitive to offsets in reverse contrast stimuli. A cell's response to a vernier stimulus in which both bars are bright can be predicted by the shape of its orientation tuning curve, if the vernier stimulus is approximated by a single bar with an orientation equal to that of a line joining the midpoints of the two component bars (Swindale & Cynader, 1986). This approximation did not hold for the reverse contrast condition: orientation tuning curves for compound barswere broad and shallow, rather than bimodal, with peaks up to 40 deg from the preferred orientation. Results from simple cells were compared with predictions made by a linear model of the receptive field. The model predicted the V-shaped tuning curves found for reverse contrast stimuli. It also predicted that absolute values of tuning slopes for vernier offsets in reverse contrast stimuli might sometimes be higher than with normal stimuli. This was observed in some simple cells. The model was unable to explain the shape of orientation tuning curves for compound bars, nor could it explain the breakdown of the equivalent orientation approximation.

The responses of inferior temporal (IT) neurons may depend on the behavioral context of the stimuli; e.g. in Konorski tasks responses to two successively presented physically identical stimuli can be markedly different. This effect has been interpreted as being linked to the behavioral task, and to be involved in short-term memory and/or the temporal comparison of successively presented stimuli. We tested whether this behavioral context effect also occurs when the monkey is not executing a Konorski task, i.e. no temporal comparison of stimuli is being performed. Responses of the same IT neurons under two behavioral conditions were compared using the same temporal stimulus sequence (but different stimuli): a Konorski task and a Fixation task. We found that the occurrence of the behavioral context effect did not depend on the execution of the short-term memory task. The observed decline in the level of responses to repeated presentation of similar stimuli is interpreted as being a passive mechanism involved in recency detection, which occurs even if the recency information is not useful for the task. The importance of these results in the interpretation of “task-related” neuronal responses is discussed.

The responsiveness of luminosity-type horizontal cells, recorded intracellularly from isolated hybrid bass retinas, decreased after superfusion for 2 h in constant darkness. Responsiveness was subsequently increased (light-sensitized) up to 10-fold after exposure to several short (~0.5 min) periods of continuous illumination. The increase in horizontal cell responsiveness following light-sensitization was due to an increase of peak response amplitude rather than a reduction of peak response time. The increased responsiveness after light-sensitization was intensity-dependent with brighter sensitizing stimuli causing a greater increase than dimmer stimuli. The extent of LHC dark-suppression was affected by the time of day, being greater when induced during the night than during the day. However, there was no significant difference in horizontal cell responsiveness after light-sensitization in retinas studied during the night compared to those studied during the day The responsiveness of light-sensitized horizontal cells from isolated hybrid bass retinas was found to be suppressed by relatively brief periods of darkness. The responsiveness of horizontal cells, that were first light-sensitized, decreased by more than 50% following only 5 min of darkness. Suppression of light-sensitized horizontal cell responsiveness after such a short time in the dark has not been described in other teleost retinas. The suppression of light-sensitized horizontal cell responsiveness in hybrid bass retinas may be rapid in comparison to other teleosts.

Horizontal cells of the carp retina alter their synaptic connections with cones during dark and light adaptation. At light onset, dendrites of horizontal cells, which are positioned laterally at the ribbon synapse, form “spinules,” little processes with membrane densities. Spinules are retracted again during dark adaptation. Spinule retraction is also elicited upon glutamate application to the retina. In the present study, we address the question whether calcium/calmodulin-dependent pathways are involved in dark- and glutamate-evoked spinule retraction. Light-adapted retinas were isolated and subsequently dark adapted during incubation in media of different calcium concentrations. Spinule retraction was clearly blocked in low-calcium solutions (5 μM and 50 nM CaCl2). Incubation in medium containing cobalt chloride (2 mM) had the same effect. Both treatments blocked the glutamate-induced spinule retraction as well. These results indicate that spinule retraction is induced by a calcium influx into horizontal cells. To investigate whether calmodulin, the primary calcium receptor in eukaryotic cells, is present at the site of spinule formation, light- and dark-adapted retinas, embedded in LR White resin, were labelled with an antibody against calmodulin and gold-conjugated secondary antibodies. Horizontal cell dendrites at the ribbon synapse revealed strong calmodulin immunoreactivity, which was more than twice as high in light- as in dark-adapted retinas. The incubation of isolated retinas with the calmodulin antagonists W5 and W13 inhibited spinule retraction. In summary, these results suggest that spinule retraction may be regulated by calcium influx into horizontal cells and subsequent calcium/calmodulin-dependent pathways.

A neural network model is developed to explain how visual thalamocortical interactions give rise to boundary percepts such as illusory contours and surface percepts such as filled-in brightnesses. Top-down feedback interactions are needed in addition to bottom-up feed-forward interactions to simulate these data. One feedback loop is modeled between lateral geniculate nucleus (LGN) and cortical area V1, and another within cortical areas V1 and V2. The first feedback loop realizes a matching process which enhances LGN cell activities that are consistent with those of active cortical cells, and suppresses LGN activities that are not. This corticogeniculate feedback, being endstopped and oriented, also enhances LGN ON cell activations at the ends of thin dark lines, thereby leading to enhanced cortical brightness percepts when the lines group into closed illusory contours. The second feedback loop generates boundary representations, including illusory contours, that coherently bind distributed cortical features together. Brightness percepts form within the surface representations through a diffusive filling-in process that is contained by resistive gating signals from the boundary representations. The model is used to simulate illusory contours and surface brightnesses induced by Ehrenstein disks, Kanizsa squares, Glass patterns, and cafe wall patterns in single contrast, reverse contrast, and mixed contrast configurations. These examples illustrate how boundary and surface mechanisms can generate percepts that are highly context-sensitive, including how illusory contours can be amodally recognized without being seen, how model simple cells in V1 respond preferentially to luminance discontinuities using inputs from both LGN ON and OFF cells, how model bipole cells in V2 with two colinear receptive fields can help to complete curved illusory contours, how short-range simple cell groupings and long-range bipole cell groupings can sometimes generate different outcomes, and how model double-opponent, filling-in and boundary segmentation mechanisms in V4 interact to generate surface brightness percepts in which filling-in of enhanced brightness and darkness can occur before the net brightness distribution is computed by double-opponent interactions.

The synaptic connections of amacrine cells synthesizing or accumulating serotonin in the retina of the cane toad, Bufo marinus, were studied by using preembedding double-labeling electron-microscopic immunocytochemistry. The binding sites of an anti-serotonin antibody were revealed by the diaminobenzidine reaction, whilst a colloidal gold-conjugated secondary antibody was used to detect an antibody to phenylalanine hydroxylase. Since the latter antibody recognizes tryptophan 5-hydroxylase, one of the synthesizing enzymes for serotonin, as well as tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis, the double labeling of the present study enabled us to identify three groups of labeled profiles at the ultrastructural level. The profiles of serotonin-synthesizing amacrine cells contained both diaminobenzidine reaction product and colloidal gold particles, whilst those of serotonin-accumulating and dopaminergic amacrine cells contained only diaminobenzidine reaction product or colloidal gold particles, respectively. The synapses of serotonin-synthesizing or serotonin-accumulating amacrine cells were distributed all through the inner plexiform layer of the retina. The profiles of serotonin-synthesizing amacrine cells predominantly received synapses from, and made synapses onto, unlabeled amacrine cell dendrites. They also received synapses from, and made synapses onto, bipolar cell terminals. They also made synapses onto presumed ganglion cell dendrites. However, the profiles of serotonin-accumulating cells made synapses only with unlabeled amacrine cell processes. There were close contacts between the profiles of serotonin-synthesizing and serotonin-accumulating amacrine cells. No synaptic relationships were observed between dopaminergic and serotonin-synthesizing or serotonin-accumulating amacrine cells. These observations indicate that serotonin-synthesizing amacrine cells and serotonin-accumulating amacrine cells in the retina of Bufo marinus are involved in different microcircuits in visual information processing.

We evaluated the dynamic aspects of the orientation tuning of the input to cat visual cortical neurons by analyzing the postsynaptic potentials (PSPs) evoked by flashing bars of light. The PSPs were recorded using in vivo whole-cell technique, and we analyzed the orientation tuning during subsequent temporal windows after stimulus onset and offset. Our results show that the amplitudes of the postsynaptic potential are reliably tuned to orientation and matching that of the spike responses only during certain temporal windows. During the first 100 ms after stimulus presentation, orientation tuning of the membrane potential underwent regular changes. Within particular intervals, orientation tuning of the input was much sharper than that estimated according to the whole response. In most cells, optimal orientation was usually stable over the whole period. In several cells which had a second hump of EPSPs in the response, this second hump was tuned to the same orientation as the first one, but always showed sharper tuning. Estimation of the integration time revealed sufficient delay between the appearance of EPSPs and spikes, to let inhibition influence spike generation. These results show that orientation selectivity of the input to cortical cells is a dynamic function, and also indicate the possibility of temporal coding in the visual system.

The neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4/5 are important in a variety of developmental processes in the peripheral and central nervous systems. These molecules bind to a low-affinity receptor and to distinct high-affinity receptors. The high-affinity receptor for NGF is the proto-oncogene product, p140trkA(trkA). Isoforms of p140trkA, p145trkB(trkB), and p140trkC(trkC), are the primary high-affinity receptors for BDNF and NT-3, respectively. We evaluated the developmental regulation of the high-affinity neurotrophin receptors in the rat retina using polyclonal antibodies directed to a highly conserved region of the C-terminus of the p140trkA isoforms (pantrk) and antibodies directed to unique amino-acid sequences of p140trkA, p145trkB, and p140trkC. Immunoreactivities for trkA and trkB, as well as pantrk, were detected in the developing retina and showed similar distributions. At similar antibody concentrations, trkC immunoreactivity was not detected. In the embryo, immunoreactivities were present in cells located throughout the neuroblastic retina, especially in the inner retinal layers, and in fibers in the nerve fiber layer and optic nerve. In the newborn retina, immunoreactivities for these two receptor isoforms were localized to numerous somata in the inner nuclear layer (INL), as well as to cells in the ganglion cell layer (GCL) and axons in the nerve fiber layer and optic nerve. A similar pattern of immunostaining persisted throughout the first postnatal week. By postnatal day-10, immunostaining was confined to large-diameter cells in the GCL, both heavily stained and lightly stained cells in the INL and a plexus of processes in the inner plexiform layer (IPL). In the adult retina, specific immunoreactivity was present in sparsely distributed, lightly and moderately stained, large cells in the GCL, numerous lightly and moderately stained cells throughout the INL and in plexuses of processes in the IPL and outer plexiform layer. Specific immunostaining of photoreceptor cells was not observed. These observations indicate that high-affinity receptors for the neurotrophins are expressed in cells of the inner retina, including ganglion cells, during the period of retinal development. This is congruent with roles for neurotrophins in such processes as survival, differentiation and synapse formation of cells in the developing visual system.

The present study examined GABA immunoreactivity within the retinopetal nucleus isthmo-opticus (NIO) of the pigeon centrifugal visual system (CVS) using light- (immunohistofluorescence, peroxidase anti-peroxidase: PAP) and electron- (postembedding GABA immunogold) microscopic techniques. In some double-labeling experiments, the retrograde transport of the fluorescent dye rhodamine β−isothiocyanate (RITC) after its intraocular injection was combined with GABA immunohistofluorescence. GABA-immunoreactive (-ir) somata were demonstrated within the neuropilar zone of the NIO adjacent to the centrifugal cell laminae whereas the centrifugal neurons were always immunonegative. A quantitative ultrastructural analysis was performed which distinguished five categories of axon terminal profiles (P1–5) on the basis of various cytological criteria: type of synaptic contact (symmetrical or asymmetrical); shape, size, and density of synaptic vesicles as well as the immunolabeling (positive or negative), size of profile and appearance of hyaloplasm. Numerous GABA-ir afferents to centrifugal neurons via axon terminal types P2a, P2c, and P3 were observed which comprised 47.1% of the total input. Moreover, the data suggest that some of the P2a terminals, which make up 26.4% of the input, stem from the intrinsic GABA-ir interneurons, whereas the latter receive P1, P3, but also P2 terminal input, indicating that interneurons may contact other interneurons via type P2a axon terminals. The results also suggest that the GABA-ir P3 or the immunonegative P1b and P5 axon terminals are of extrinsic origin arising from cells in the optic tectum whereas the P2c and P4 axon terminals are associated with extra-tectal input to the NIO. The GABAergic innervation of centrifugal neurons within the NIO may be the basis for the demonstrated facilitatory effect of the centrifugal output upon ganglion cell responses. This is relevant to hypotheses regarding CVS involvement in attentional mechanisms through selective enhancement of retinal sensitivity depending on the location of meaningful or novel stimuli.

The cholinergic identity of retinal starburst amacrine neurons is well established, but recent evidence suggests that these cells are GABAergic as well. Confirmation of this dual transmitter function requires the demonstration of glutamate decarboxylase (GAD), the biosynthetic enzyme for GABA, within starburst cells. The current work was undertaken to determine whether rabbit retinal starburst amacrine neurons contain either of the two known isoforms of GAD. To do this, we have examined the localization of the following: (1) the 65-kDa isoform of GAD; (2) the 67-kDa isoform of GAD; (3) choline acetyltransferase; and (4) the fluorescent dye DAPI, a marker for cholinergic amacrine cells. In addition, we labeled displaced starburst neurons directly, by injecting them with Lucifer Yellow in vitro. Four strata within the inner plexiform layer contained immunoreactive GAD65. A non-GAD65-immunoreactive zone separated the two innermost strata (G3 and G4); this zone contained (1) the dendrites of individual Lucifer Yellow-injected, displaced starburst amacrine cells; (2) dendrites immunoreactive for choline acetyltransferase; and (3) processes of DAPI-labeled amacrine cells. Immunoreactive GAD67 appeared in the same strata that contained GAD65, and in at least two additional strata, one of which lay at precisely the same depth as the proximal cholinergic stratum. In addition, the somas of displaced starburst cells were strongly immunoreactive for GAD67, but not for GAD65. These results demonstrate (1) that displaced starburst amacrine cells contain the 67-kDa isoform of GAD, but not the 65-kDa isoform; and (2) that the dendrites of starburst (67-kDa GAD) amacrines, and the dendrites of 65-kDa-GAD-containing amacrines, occupy different strata within the inner plexiform layer. Thus, displaced starburst cells do contain GAD, and can, presumably, manufacture GABA. The reasons for their preferential use of the 67-kDa GAD isoform remain to be elucidated.

Rotundal neurons in pigeons (Columba livia) were examined for the effects of glutamate and its agonists NMDA and AMPA, antagonists CPP and CNQX, as well as of GABA and its antagonist bicuculline, on visual and tectal stimulation-evoked responses. Glutamate applied by iontophoresis excited all 48 rotundal cells tested, and this excitation was blocked by CNQX but not by CPP in 98% of cases, with 2% of cells being blocked by either CNQX or CPP. Out of 21 cells excited by AMPA, 20 were also excited by NMDA, indicating that AMPA and NMDA receptors may coexist in most rotundal cells. Action potentials were evoked in 36 additional cells by electrical stimulation applied to the tectum and they were also blocked by CNQX but not CPP. Visual responses recorded from a further eight luminance units and 21 motion-sensitive units were also blocked by CNQX and not CPP. On the other hand, GABA inhibited visual responses as well as responses evoked by tectal stimulation. An inhibitory period following tectal stimulation was eliminated by bicuculline. Taken together, these results indicate that glutamate may be an excitatory transmitter acting predominantly through non-NMDA receptors (AMPA receptors) in tectorotundal transmission. Meanwhile, GABA may be an inhibitory transmitter in the pigeon nucleus rotundus.

The modulatory influence of pretectal neurons on retino-geniculate transmission in the cat was studied by cross-correlation analysis of single-unit activity simultaneously recorded from the dorsal lateral geniculate nucleus (dLGN) and the pretectum (PT) and with reversible inactivation of the PT by GABA microiontophoresis during simultaneous visual stimulation of PT and dLGN neurons. Visually induced population activity in PT nuclei was achieved by a moving (or counterphasing) grating which was presented in the background of the light spot used to stimulate the dLGN neuron. As a control, the light spot was presented on a stationary grating to avoid stimulation of PT neurons but to yield the same illumination of the background. Extracellularly recorded dLGN relay cells of the X- and Y-type were found to be differentially affected by the PT-dLGN projection. During visual stimulation of PT cells, X cells were strongly inhibited and this effect was significantly reduced during PT inactivation. By contrast, the visual responses of most Y cells were affected neither by PT stimulation nor by PT inactivation. In addition, the temporal structure of spike patterns during the light response was examined with autocorrelograms and spike-interval distributions. X-on cells often exhibited a multimodal interval distribution and oscillatory type of activity. During stimulation of the PT interval distributions changed in a characteristic manner and oscillations disappeared. Both effects could be almost totally cancelled by PT inactivation. By contrast, the temporal structure of Y-cell responses was not affected. Our results demonstrate for the first time a pretectal modulation of retino-geniculate transmission in cat dLGN which is clearly different for X and Y cells. This influence seems to be mediated via (inhibitory) interneurons, since we found no indication for a direct coupling between PT and dLGN units. This projection might contribute to the well-known phenomenon of saccadic suppression.

Though there is considerable evidence that dopamine is an important retinal neuromodulator that mediates many of the changes in the properties of retinal neurons that are normally seen during light adaptation, the mechanism by which dopamine release is controlled remains poorly understood. In this paper, we present evidence which indicates that dopamine release in the retina of the tiger salamander, Ambystoma tigrinum, is driven excitatorily by a cholinergic input. We compared the effects of applying carbachol to those of dopamine application on the responses of rods, horizontal cells, and bipolar cells recorded intracellularly from the isolated, perfused retina of the tiger salamander. Micromolar concentrations of dopamine reduced the amplitudes of rod responses throughout the rods' operating range. The ratio of amplitudes of the cone-driven to rod-driven components of the responses of both horizontal and bipolar cells was increased by activation of both D1 and D2 dopamine receptors. Dopamine acted to uncouple horizontal cells and also off-center bipolar cells, the mechanism in the case of horizontal cells depending only upon activation of D1 receptors. Carbachol, a specific cholinomimetic, applied in five- to ten-fold higher concentrations, produced effects that were essentially identical to those of dopamine. These effects of carbachol were blocked by application of specific dopamine blockers, however, indicating that they are mediated secondarily by dopamine. We propose that the dopamine-releasing amacrine cells in the salamander are under the control of cells, probably amacrine cells, which secrete acetylcholine as their transmitter.

We investigated the recovery of light-adaptive spinule formation following dopamine depletion with intraocular injection of 6-hydroxydopamine (6-OHDA) and subsequent neogeneration of dopamine interplexiform cells (DA-IPC) at the marginal zone. DA-IPCs were gone by 2 weeks postinjection and appeared at the marginal zone by 6 weeks postinjection, at which time DA-IPC neurites grew toward the central retina, reaching within 0.5 mm of the central retina by 1 year. Retinas from day time, light-adapted fish at 2 weeks, 4 weeks, 3 months, and 1 year postinjection with 6-OHDA were processed for pre-embedding tyrosine hydroxylase immunoreactivity (TOH-IR) and compared to sham-injected and control retinas at the electron-microscopical (EM) level. Only 6-OHDA fish that tilted markedly toward the injected eye were used for these experiments. The tilt mimics the dorsal light reaction, indicating a 2–2.5 log unit increase in the photopic sensitivity of the 6-OHDA eye. Spinule formation was reduced by about 60% in the 2- and 4-week 6-OHDA retinas, but returned to control levels throughout the entire retina of 3-month and 1 year 6-OHDA retinas even though the central region of these retinas contained no detectable TOH-IR. Intraocular injection with 10 μM SCH 23390 (a Dl antagonist) reduced light-adaptive spinule formation by 50% both in control eyes as well as those eyes that were 3 months post 6-OHDA injected. The full return of spinule formation with only partial reinnervation of the retina with DA-IPC processes and their subsequent inhibition by SCH 23390 indicates that dopamine diffused large distances within the retina to regulate this synaptic plasticity (i.e. displayed volume transmission). Also, since all 6-OHDA injected fish displayed an increased photopic sensitivity in the injected eye when sacrificed, we suggest that horizontal cell spinules are not required for photopic luminosity coding in the outer retina.