Relay cells of the lateral geniculate nucleus, like those of other thalamic nuclei, manifest two distinct response modes, and these represent two very different forms of relay of information to cortex. When relatively hyperpolarized, these relay cells respond with a low threshold Ca2+ spike that triggers a brief burst of conventional action potentials. These cells switch to tonic mode when depolarized, since the low threshold Ca2+ spike, being voltage dependent, is inactivated at depolarized levels. In this mode they relay information with much more fidelity. This switch can occur under the influence of afferents from the visual cortex or parabrachial region of the brain stem. It has been previously suggested that the tonic mode is characteristic of the waking state while the burst mode signals an interruption of the geniculate relay during sleep. This review surveys the key properties of these two response modes and discusses the implications of new evidence that the burst mode may also occur in the waking animal.

Modes of storage and mechanisms of formation of 11-cis retinoids in the eyes of animals vary widely among the major phyla. We here describe evidence from two species of macruran decapod crustacea that point to different processes from those known in insects, the other group of arthropods for which there is extensive data. The eyes of the lobster (Homarus) contain about 300 pmol of retinal, somewhat less free retinol, and variable amounts (up to 1000+ pmol) of two retinyl esters, over 90% of which contain retinol in the 11-cis configuration. The major ester contains the long chain, polyunsaturated fatty acid docosahexaenoate (C22:6), but retinyl oleate (C18:1) is also present. Crayfish (Procambarus) contain the same retinyl esters, although in much smaller amounts. Homogenates of the eyes of both species are capable of isomerizing all-trans retinyl docosahexaenoate to the 11-cis configuration without using the energy of light. Crude fractionation of homogenates shows isomerase activity associated with membranes. The reaction mechanism has not been explored in detail, but on the basis of present evidence it may be similar to that found in vertebrate pigment epithelium. It is clearly different from the light-dependent processes known in insects (Hymenoptera and Diptera) and cephalopod mollusks, where isomerization takes place at the level of the aldehyde and 11-cis retinyl esters are not present as major storage reserves.

Monocular deprivation in adult macaques produces a rapid down-regulation in GABA and GABAA receptor subunit immunoreactivity in deprived-eye columns of primary visual cortex (V1) but a significantly delayed GABA reduction in deprived layers of the dorsal lateral geniculate nucleus (LGN). These findings, suggesting that normal inhibitory neurotransmission persists in LGN at a time when V1 inhibitory mechanisms are greatly altered, are consistent with physiological studies that have demonstrated a greater degree of functional plasticity in V1 than in LGN. Nonetheless, functional adaptation to partial loss of visual input has been detected in the LGN, indicating that synaptic plasticity takes place in this nucleus. In the present study, evidence for early changes in inhibitory neurotransmission were examined with immunocytochemical methods to determine if, in the absence of early GABA regulation, GABAA receptor subunits in macaque LGN are affected by adult deprivation. Immunoreactivity for α1 and β2/3 subunits of the GABAA receptor was intense within the magnocellular layers and more modest in the parvocellular layers and intercalated layers. In all layers, immunoreactivity was present in the cytoplasm and along the surfaces of relatively large somata and in dense tangles of processes in the neuropil. Double-labeling experiments demonstrated that somata and processes immunoreactive for α 1 and β2/3 were surrounded by GABA terminals but no cell intensely immunoreactive for either subunit expressed immunoreactivity for GABA, itself. Following periods of monocular deprivation by tetrodotoxin (TTX) injection for 4 days or longer, layers deprived of visual activity displayed levels of α 1 and β2/3 immunoreactivity markedly lower than those displayed by the adjacent, normally active layers. Such changes were greater as the period of deprivation increased. The changes included a loss of immunostaining in and around somata and in many neuropil elements of deprived layers. These data indicate that GABA and GABAA receptor subunits α 1 and β2/3 are expressed by separate populations of neurons in macaque LGN that are differentially regulated by visual activity. The findings suggest that rapid, activity-dependent regulation of postsynaptic receptors represents one mechanism for altering synaptic strength in the adult macaque visual system.

Autoradiography with 125I-neurotensin in normal and enucleated hamsters was used to define the distribution of receptors for this peptide in the superficial layers of the superior colliculus (SC). Neurotensin binding sites were densely distributed in the stratum griseum superficiale (SGS), and results from the enucleated animals indicated that they were not located on retinal axons. The effects of neurotensin on individual superficial layer cells were tested in single-unit recording experiments. Neurotensin was delivered via micropressure ejection during visual stimulation (n = 75 cells), or during electrical stimulation of either the optic chiasm (OX; n = 47 cells) or visual cortex (CTX; n = 29 cells). In comparison with control values, application of neurotensin decreased visual responses of all SC cells tested to 54.1 ± 34.9% (mean ± standard deviation; range of decrement 7.5 to 100%; nine cells showed no effect or an increase in visual activity, which for four of these was ≥30%). Neurotensin application also reduced responses to electrical stimulation of either OX or CTX, respectively, to 65.8 ± 36.5% of control values (range of decrement 2.6 to 97.4%; 12 neurons showed a weak increment ≤ 30%) and 68.0 ± 38.5% (range of decrement 3.3 to 100%; five cells showed no effect or an increment, in one case ≥ 30%). Of the 25 neurons tested with both OX and CTX stimulation, the correlation of evoked response suppression by neurotensin was highly significant (r = 0.70; P < 0.001). This suggests that the suppressive effects of neurotensin were common to both pathways. To test whether the inhibitory effects of neurotensin were presynaptic or postsynaptic, Mg2+ ions were ejected iontophoretically to abolish synaptic responses, and the neurons (n = 16) were activated by iontophoresis of glutamate and then tested with neurotensin. Neurotensin reduced the glutamate-evoked responses to an average 59.3 ± 37.9% of control values (range 2.3 to 92.5%; one cell showed an increment >30%). This result suggests that the site of action of neurotensin is most likely postsynaptic.

Retinas of the nocturnal geckos, Hemidactylus turcicus, Hemidactylus garnotii, and Teratoscincus scincus, were studied with microspectrophotometry and immunocytochemistry against various visual pigment epitopes to reveal UV-sensitive photoreceptors. From 6–20% of the thinner members of type C double photoreceptors, earlier believed to be blue-sensitive, were found to contain a UV-absorbing visual pigment with λmax at 363–366 nm. The pigment had bleaching and dichroic properties typical of other photoreceptor cell types of the retina. Presumptive UV-sensitive cells in retinal sections were “negatively” labeled as they did not react with either the cone-specific monoclonal antibody COS-1 or with the anti-rhodopsin polyclonal serum AO, which together labeled all of the remaining photoreceptor types (green-sensitive A singles, B doubles, and thicker members of C doubles, as well as the blue-sensitive majority of thinner members of C doubles). UV cells were moderately stained with the mAb K42–41 produced against the 5–6 loop of bovine rhodopsin, which also moderately labeled blue-sensitive cells. mAb OS-2 strongly stained all outer segments, including the UV-sensitive ones. Similarities between gecko UV visual pigments, and UV visual pigments of other vertebrates, as well as possible functional significance of these cells are discussed.

The light-driven pupil mechanism, consisting of an assembly of mobile pigment granules inside the photoreceptor cells, has been investigated by in vivo reflection microspectrophotometry in wild type (WT) Drosophila and in the photoreceptor mutants inaC and trp. The pupillary response of a dark-adapted WT eye to a step in light is a monophasic reflectance increase reaching a plateau after ca. 15-s light adaptation. This reflectance change is due to photoreceptor pigment granules that accumulate near the tips of the rhabdomeres under light adaptation and that are withdrawn towards the periphery in the dark (Franceschini & Kirschfeld, 1976). The step response of the pupil mechanism of inaC is triphasic. Strikingly, the reflectance level at light onset is distinctly higher than that in WT, due to a partly aggregated state of the photoreceptor pigment granules near the rhabdomere tips that persists in the dark-adapted state, in line with direct calcium measurements of Peretz et al. (1994b). The step response of the pupil mechanism of inaC is slightly elevated compared to that of WT. The step response in trp is a transient, biphasic reflectance change, approximating a log normal function. This function is also a good approximation of the pulse response in WT and inaC. The intensity range of pupillary sensitivity is about 4 log unit. The range of inaC compared to that of WT is slightly (≈0.5 log unit) shifted towards lower intensities, but that in trp is strongly shifted to higher intensities (≈2.5 log unit). The results can be interpreted with the present knowledge of the primary steps in fly phototransduction and the hypothesis that the local intracellular calcium concentration determines the position of the pigment granules, and hence are in line with the notion that the pupil can be used as a qualitative Ca2+ probe.

Previous studies report that background luminance flicker, which is asynchronous with signal averaging, reduces the amplitude and increases the latency of the pattern-onset visual evoked potential (VEP). This effect has been attributed to saturation of the magnocellular (m-) pathway by the flicker stimulus. In the current study, we evaluate this hypothesis and further characterize this effect. We found that flicker had similar effects on the pattern-onset and pattern-reversal VEP, suggesting that the reversal and onset responses have similar generators. Chromatic flicker decreased latency of the chromatic VEP whereas luminance flicker increased peak latency to luminance targets. This result indicates that luminance flicker saturates a rapidly conducting m-pathway whereas chromatic flicker saturates a more slowly conducting parvocellular (p-) pathway. Finally, evoked potentials to chromatic and luminance stimuli were recorded from 34 electrodes over the scalp in the presence of static and asynchronously modulated backgrounds. An equivalent dipole model was used to assess occipital, parietal, and temporal lobe components of the surface response topography. Results showed that chromatic flicker reduced activity to a greater extent in the ventral visual pathway whereas luminance flicker reduced activity to a greater extent in the dorsal visual pathway to parietal lobe. We conclude that the VEP to isoluminant color and luminance stimuli contains both m- and p-pathway components. Asynchronous flicker can be used to selectively reduce the contribution of these pathways to the surface recorded VEP. Our results provide evidence of parallel pathways in the human visual system, with a dorsal luminance channel projecting predominantly to the posterior parietal lobe and a ventral color channel projecting predominantly to inferior temporal lobe.

Variations in velocity detection thresholds for full-field visual rotation about various axes are compatible with a simple channel-based system for coding the axis and velocity of the rotation (Harris & Lott, 1995). The present paper looks at the frame of reference for this system. The head-centered, craniotopic reference system and the retinal-based, retinotopic reference systems were separated by using eccentric eye positions. We measured the threshold for detecting full-field visual rotation about a selection of axes in the sagittal plane with the eyes held either 22½ degs up, straight ahead or 22½ degs down in the head. The characteristic features of the variation in detection thresholds did not stay stable in craniotopic coordinates but moved with the eyes and were constant in retinotopic coordinates. This suggests that the coding of head rotation by the visual system is in retinotopic coordinates.

Using patch-clamp recording in combination with reverse transcriptase-polymerase chain reaction (RT-PCR), we show in individual bipolar cells acutely dissociated from the adult rat retina a correlation between the expression of the GABAA receptor ρ1 subunit mRNA and a bicuculline-resistant, diazepam-insensitive component of the GABA-activated whole-cell current response. This “GABAC-like” response, contributing to approximately 42% of the GABA-activated whole-cell current and displaying variable sensitivity to picrotoxin, was found in bipolar cells but not in any of the ganglion cells examined. Expression profiling of GABAA receptor subunit mRNAs in individual electrophysiologically tested retinal neurons revealed that, while both bipolar cells and ganglion cells may express numerous GABAA receptor subunit isoforms, including that of ρ2, the expression of the ρ1 subunit was strictly limited to bipolar cells. We propose a possible link between the presence of a receptor with GABAC-like pharmacological profile and the expression of the retina-specific ρ1 subunit isoform. The results presented in this study constitute the first direct demonstration of such a correlation at the single-cell level.

Agrin is a large extracellular matrix protein that directs the accumulation of acetylcholine receptors at the neuromuscular junction. Recent evidence suggests that agrin may be involved in organizing synapses in the visual system as well. Focussing on the pathway that controls accommodation and pupilloconstriction, this study examined the temporal pattern of agrin expression with reference to the organization of cholinergic synapses between embryonic chick Edinger-Westphal and ciliary ganglion neurons. In situ hybridization with an S35-labeled agrin cRNA probe was used to characterize agrin expression in the Edinger-Westphal nucleus during development. Agrin mRNA was detected in the Edinger-Westphal nucleus at all time points studied, from embryonic day 7 (E7, Hamburger and Hamilton stage 31) through newly hatched chicks. Throughout this period, agrin mRNA expression in Edinger-Westphal neurons was lower than in nearby oculomotor and trochlear neurons, suggesting that cells projecting to neuronal targets may require less agrin than those projecting to muscle. Agrin mRNA expression in the Edinger-Westphal nucleus at E7, E8, E9, and E10 was significantly higher than at E12. The early appearance of agrin mRNA coincides with the period during which acetylcholine receptors are being organized on ciliary ganglion neurons, consistent with the possibility that agrin contributes to neuron-neuron synapse formation in this pathway.

The excitatory receptive-field centers of On-Off directionally selective (DS) ganglioncells of the rabbit retina correspond closely to the lateral extent of their dendritic arborizations. Some investigators have hypothesized from this that theories for directionalselectivity that entail a lateral spread of excitation from outside the ganglion cell dendritic tree, such as from starburst amacrine cells, are therefore untenable. We show herethat significant motion facilitation is conducted from well outside the classical excitatory receptive-field center (and, therefore, dendritic arborization) of On-Off DS ganglioncells for preferred-direction, but not null-direction moving stimuli. These results are consistent with a role in directional selectivity for cells with processes lying beyond the On-Off ganglion cell's excitatory receptive-field center. These results also highlight the fundamental distinction in retinal ganglion cell receptive-field organization between classical excitatory mechanisms and those that facilitate other excitation without producing directly observable excitation by themselves.

The peptide, neurotensin, is found in a class of amacrine cells synapsing chiefly withother amacrine cells in the chicken retina (Li & Lam, 1990; Watt et al., 1991). Toinvestigate the possible effects of neurotensin, we have used Ca2+ imaging to measure cytosolic Ca2+ concentrations in cultured chick amacrine cells. Following a delay of about 2 min, neurotensin (300 nM) induced oscillations in Ca2+ concentration that typically had a period of 2 min and peak values of about 300 nM when averaged over the cell body. The phospholipase C inhibitors U-73, 112 and 4′-bromophenacyl bromide terminated oscillations induced by neurotensin but the protein kinase inhibitors H7 and staurosporine did not inhibit oscillations, increasing their frequency instead. In the absence of external Ca2+, neurotensin induced only a single Ca2+ transient, much briefer than when external Ca2+ was present. Together these results suggest that neurotensin activates phospholipase C, thereby producing IP3 that triggers Ca2+ release from an internal store. Although this released Ca2+ contributes to periodic Ca2+ peaks, the majority of cytosolic Ca2+, even in the first peak, comes from Ca2+ influx across the plasmalemma.

Although it is well known that neurotransmitters mediate neuron-to-neuron communication, it is becoming clear that neurotransmitters also affect glial cells. However, knowledge of neuron-to-glial signalling is limited. In this study, we examined the effects of the glutamate agonist N-methyl-D-aspartate (NMDA) on Müller cells, the predominant glia of the retina. Our immunocytochemical studies and immunodetection by Western blotting with monoclonal antibodies specific for the NMDAR1 subunit provided evidence for the expression by human Müller cells of this essential component of NMDA receptor-channels. Under conditions in which potassium currents were blocked, NMDA-induced currents could be detected in perforated-patch recordings from cultured and freshly dissociated human Müller cells. These currents were inhibited by competitive and non-competitive blockers of NMDA receptor-channels. Extracellular magnesium reduced the NMDA-activated currents in a voltage-dependent manner. However, despite a partial block by magnesium, Müller cells remained responsive to NMDA at the resting membrane potential. Under assay conditions not blocking K+ currents, exposure of Müller cells to NMDA was associated with an MK-801 sensitive inhibition of the inward-rectifying K+ current (IK(IR)), the largest current of these glia. This inhibitory effect of NMDA appears to be mediated by an influx of calcium since the inhibition of IK(IR) was significantly reduced when calcium was removed from the bathing solution or when the Müller cells contained the calcium chelator, BAPTA. Inhibition of the Müller cell KIR channels by the neurotransmitter glutamate is likely to have significant functional consequences for the retina since these ion channels are involved in K+ homeostasis, which in turn influences neuronal excitability.

This study was performed in order to establish whether selective depletion of somatostatin (SS) in the rat primary visual cortex obtained by cysteamine (CSH) administration results in changes of visual evoked potentials (VEPs). VEPs in response to a contrast reversal (0.5 Hz) of an optimal sinusoidal grating (0.1 cycle/deg, contrast 90%, mean luminance 15 cd/m2) were recorded from different layers of the binocular portion of the primary visual cortex of anesthetized rats with saline injection as well as before and after CSH treatment (90 mg/kg, s.c). VEPs of CSH treated rats, as compared to those obtained either in saline-injected animals or before drug administration, are reduced in amplitude at intermediate cortical layers whereas they are increased at deeper layers. VEP changes depend on CSH treatment and not on the extended anesthesia since no alterations in the VEP profile can be observed in saline-injected animals maintained in the same experimental condition. Forty-eight hours following CSH treatment, the VEP profile is comparable to that of saline-injected animals. Immunocytochemical analysis of the visual cortex of rats recorded 7 h after CSH treatment shows a 20–30% reduction in the number of SS-containing cortical cells. The highest reduction can be observed in cortical layer 5 although a significant decrease is also found in layers 2–3. In contrast, the pattern of SS immunoreactivity of the visual cortex of rats recorded 48 h after CSH administration is similar to that obtained in control conditions. These results indicate that a selective toxin for somatostatinergic systems induces a transient decrease of SS-containing cell number in selected cortical layers. Accordingly, CSH can serve as a useful pharmacological tool for the study of somatostatinergic function in the rat visual cortex since changes in VEPs can be related to a reduction of somatostatinergic neurons associated to CSH treatment. In particular, the present results suggest that one of the possible actions of somatostatinergic neurons in the rat visual cortex is to modulate the excitatory-inhibitory balance.

We studied the anatomical substrates of spatial vision in a New World monkey, the marmoset Callithrix jacchus. This species has good visual acuity and a foveal specialization which is qualitatively similar to that of humans and other Old World primates.We measured the spatial density of retinal ganglion cells and photoreceptors, and calculated the relative numbers of these cell populations. We find that ganglion cells outnumber photoreceptors by between 2.4:1 and 4.2:1 in the fovea. The peak sampling density of ganglion cells is close to 550,000 cells/mm2. This value falls by almost 1000-fold between the fovea and peripheral retina; a value which approaches recent estimates of the centroperipheral ganglion cell gradient for human and macaque monkey retina and primary visual cortex. The marmoset shows a sex-linked polymorphism of color vision: all male and some female marmosets are dichromats. Six of the retinas used in the present study came from animals whose chromatic phenotype was identified in electrophysiological experiments and confirmed by polymerase chain reaction (PCR) amplification of cone opsin encoding genes. One animal was a trichromat and the others were dichromats. Antibodies against short wavelength-sensitive (SWS) cones labeled close to 8% of all cones near the fovea of onedichromat animal, consistent with electrophysiological evidence that the SWS system is present inall marmosets. The topography and spatial density of cone photoreceptors and ganglion cells was similar to that reported for macaque retina, and we found no obvious difference between dichromatic and trichromatic marmoset retinas. These results reinforce the view that the main determinate of primate foveal topography is the requirement for maximal spatial resolution.

Two distinct opsin-encoding cDNAs, designated MANOP1 and MANOP2, were isolated as 3′ fragments from the sphingid moth Manduca sexta. They were obtained by reverse transcription of retinal RNA and amplification with the polymerase chain reaction (PCR) using a degenerate primer designed to an amino-acid sequence conserved in arthropod opsins. The cDNA fragments labelled bands at approximately 1.8 kb on Northern blots of retinal RNA extracts. Levels of opsin message were compared in retinas from normal moths, whose diets were fortified with carotenoid precursors of the Manduca rhodopsin chromophore, 3-hydroxyretinal, and those reared on carotenoid/retinoid (vitamin A) deficient diets. The chromophore-depleted retinas contained more opsin mRNA; this was particularly true for MANOP2. Thus, the chromophore is not required for opsin gene transcription in Manduca.

The early development of the optic tract in hamsters was studied by labeling retinal axons with Dil applied to the eye, and then examining the labeled axons in flatmount preparations of the rostral brain stem. This technique permits a panoramic view of the entire retinal projection, from the chiasm to the caudal end of the superior colliculus. In the Ell embryo, retinal axons have reached the chiasm. They defasciculate as they emerge from the nerve, prior to reaching the ventral midline of the diencephalon, then converge again as they pass over to the opposite side. At the midline, many axonal trajectories crisscross, implying some shuffling of relative positions. Retinal axons are tightly bundled within the optic tract. Upon reaching the ventral border of the lateral geniculate body (LGB), they splay out over the nucleus, revealing a wavefront of pioneer axons individually distributed across the rostro-caudal extent of the LGB. Later-emerging retinal axons course over the surface of the thalamus in waves; subsequent waves of axons interdigitate between the lead fibers without fasciculating along them. Past the LGB, the axons undergo a second change in relative positions as the ribbon of fibers swerves caudally, prior to entering the superior colliculus. Retinal axons are tipped with growth cones of varying morphologies. No strong correlation is evident between the Structural complexity of the growth cone and its position within the tract. In the majority of cases, ipsilaterally and contralaterally directed axons follow a similar developmental course along the optic tract, without any indication of a temporal lag in the ipsilateral projection as claimed in earlier reports. Understanding the changes in spatial distribution of embryonic retinal axons as they navigate along the optic tract provides a further step towards elucidating how point-to-point projections form in developing sensory systems.

The turtle's optokinetic response is described by a simple model that incorporates visual-response properties of neurons in the pretectum and accessory optic system. Using data from neuronal and eye-movement recordings that have been previously published, the model was realized using algebraic-block simulation software. It was found that the optokinetic response, modelled as a simple negative feedback system, was similar to that measured from a behaving animal. Because the responses of retinal-slip detecting neurons corresponded to the nonlinear, closed-loop optokinetic response, it was concluded that the visual signals encoded in these neurons could provide sufficient sensory information to drive the optokinetic reflex. Furthermore, it appears that the low gain of optokinetic eye movements in turtles, which have a negligible velocity storage time constant, may allow stable oculomotor output in spite of neuronal delays in the reflex pathway. This model illustrates how visual neurons in the pretectum and accessory optic system can contribute to visually guided eye movements.

The activity of parietal cortex neurones primarily related to eye position (EP neurones) was studied in macaque monkeys with the aim of precisely defining the neurones' gaze fields (GF) and comparing them in two functionally different areas, MSTd and 7a. Discharge rates of single neurones in the inferior parietal lobule and in the underlying cortex of the superior temporal sulcus were recorded in two Java monkeys while the animals fixated a steady visual target positioned at several different points on a video screen. The GFs were then drawn as a regression surface fitting the mean discharge rates. Cells tonically influenced by the angle of gaze were found in both areas. The GFs most often took the form of a nearly planar surface best characterized as a ramp tilted towards a hemifield or quadrant of the visual field, shifted eccentrically with respect to the straight ahead (primary position), and with a midpoint centred between 0 deg and 20 deg of gaze eccentricity and saturation between 10 deg and 35 deg. In a minority of cases, the discharge rate was nearly maximal at the primary position and decreased to a minimum within 35 deg of eccentricity. In other instances, the GFs were peaked surfaces, limited to a restricted part of visual space. EP neurones, while showing similar gaze fields in areas MST and 7a, were found intermingled with functionally different types of cells. The results suggest that EP neurones similar to those already described in several areas of the monkey parietal cortex are present also in area MST. These cells, by signalling the degree of gaze eccentricity from the primary position, encode gaze position in an orbito-centered frame extending up to 30–35 deg from the straight-ahead. The role of EP neurones might be to supply contiguous elements with a gaze eccentricity signal required for visuo-motor processes such as the control of tracking movements.