C. Distler

Physiological and anatomical identification of the nucleus of the optic tract and dorsal terminal nucleus of the accessory optic tract in monkeys.

SummaryPhysiological and anatomical criteria were used to clearly establish the existence of a pretectal relay of visual information to the ipsilateral inferior olive in the macaque monkey. After injection of horseradish peroxidase into the inferior olivary nucleus, retrogradely labelled neurons were found in the nucleus of the optic tract (NOT) and the dorsal terminal nucleus of the accessory optic tract (DTN). The labelled cells were distributed in a sparse band arching below the margin of the brachium of the superior colliculus between the dorsal and lateral borders of the brainstem at the caudal edge of the pulvinar. Various types of cells could be distinguished. More superficially the cells were extremely spindle shaped, cells deeper within the midbrain had more compact somata. NOT-DTN neurons in the same region were also found to respond with short latencies to electrical stimulation of both the inferior olive and the optic chiasm. All neurons in the NOTDTN which were antidromically activated from the inferior olive were also found to have direction specific binocular visual responses. Such neurons were excited by ipsiversive motion and suppressed by contraversive motion, regardless of whether large area random dot stimuli moved across the visual field or small single dots moved across the fovea. Direct retinal input to these neurons was via slowly conducting fibers (3–9 m/s) from the monkeys optic tract conduction velocity spectrum. As shown previously for non-primates, NOT-DTN cells may also in the monkey carry a signal representing the velocity error between stimulus and retina (retinal slip), and relay this signal into the circuitry mediating the optokinetic reflex.

Glia Cells of the Monkey Retina—II. Müller Cells

In this paper, for the first time a quantitative description of the morphology and distribution of Müller cells in the macaque monkey retina using immunohistochemistry and high resolution confocal laser scanning microscopy is given. By their morphological features Müller cells are ideally adapted to their neuronal environment in the various retinal layers, with a dense network of horizontal processes, especially in the inner plexiform layer, and close contacts to neuronal somata especially in the outer nuclear layer and ganglion cell layer. Morphology varies with retinal eccentricity. The thickness of the inner trunk increases significantly with increasing retinal eccentricity. According to the overall thickness of the retina, Müller cells in central retina are longer than in peripheral regions. In the parafoveal region, the outer trunks of Müller cells in the outer plexiform layer are immensely elongated. These Müller fibres can reach lengths of several hundred micrometers as they travel through the outer plexiform layer from the foveal centre towards the foveal border where they enter the inner nuclear layer. Müller cell density varies between 6000 cells/mm2 in far peripheral and peak densities of > 30,000 cells/mm2 in the parafoveal retina. There is a close spatial relationship between Müller cells and blood vessels in the monkey retina, suggesting a role of Müller cells in the formation of the blood-retinal barrier, in the uptake of nutrients and the disposal of metabolites.

Alterations of Müller (glial) cells in dystrophic retinae of RCS rats.

SummaryWe have carried out a light microscopical study of Müller cells in the retinae of rats with inherited retinal dystrophy (Royal College of Surgeons rats). Isolated retinae of both control and Royal College of Surgeons rats were exposed to a Procion Yellow solution which is taken up selectively into Müller cells. The shape of the cells was then studied by confocal microscopy. Enzymatically isolated Müller cells were studied immunocytochemically with antibodies against glial fibrillary acidic protein, cathepsin D, β-amyloid precursor protein, bcl-2 protooncogene product, and glutamine synthetase. Müller cells from RCS retinae were shorter than those from control retinae, and showed a coarse hypertrophy of their distal (sclerad) processes. In Müller cells isolated from the retinae of Royal College of Surgeons rats, the expression of glial fibrilliary acidic protein, cathepsin D, β-amyloid precursor protein and bcl-2 protooncogene product was increased, and the expression of glutamine synthetase was reduced. Obviously, loss of neighbouring neurons leads to major alterations of both the shape and metabolism of Müller cells. The expression of enzymes that serve functional glio-neuronal interactions, such as glutamine synthetase, seems to be down-regulated, whereas proteins involved in cell reconstruction (cathepsin D), cell repair (possibly β-amyloid precursor protein), and protection against apoptotic cell death (bcl-2 protooncogene product), are up-regulated, together with the ‘pathological marker’ glial fibrilliary acidic protein.

Cortical projections to the nucleus of the optic tract and dorsal terminal nucleus and to the dorsolateral pontine nucleus in macaques: A dual retrograde tracing study

The nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT‐DTN) along with the dorsolateral pontine nucleus (DLPN) have been shown to play a role in controlling slow eye movements and in maintaining stable vision during head movements. Both nuclei are known to receive cortical input from striate and extrastriate cortex. To determine to what degree this cortical input arises from the same areas and potentially from the same individual neurons, we placed different retrograde tracers into the NOT‐DTN and the DLPN. In the ipsilateral cortical hemisphere the two projections mainly overlapped in the posterior part of the superior temporal sulcus (STS) comprising the middle temporal area (MT), the middle superior temporal area (MST), and the visual area in the fundus of the STS (FST) and the surrounding cortex. In these areas, neurons projecting to the NOT‐DTN or the DLPN were closely intermingled. Nevertheless, only 3–11% of the labeled neurons in MT and MST were double‐labeled in our various cases. These results indicate that the cortical input to the NOT‐DTN and DLPN arises from largely separate neuronal subpopulations in the motion sensitive areas in the posterior STS. Only a small percentage of the projection neurons bifurcate to supply both targets. These findings are discussed in relation to the optokinetic and the smooth pursuit system. J. Comp. Neurol. 444:144–158, 2002.

The pupillary light reflex in normal and innate microstrabismic cats, II: Retinal and cortical input to the nucleus praetectalis olivaris.

The anatomical substrate of the pupillary light reflex was investigated in normal and innate microstrabismic cats using anatomical methods as well as electrical stimulation. The bilateral retinal input to the nucleus praetectalis olivaris (NPO), the pretectal relay station in the subcortical pupilloconstrictor pathway, was identified to come from the ventral retina were the upper visual field is represented. Orthodromic electrical stimulation revealed that retinal information is transmitted to on-tonic neurons in the NPO mainly via slowly conducting axons probably originating from W- and X-type retinal ganglion cells. For the first time, a direct cortical input to on-tonic neurons in the NPO could be demonstrated. This cortical input originates from caudolateral parts of the occipital cortex. Putative input structures are those subdivisions of areas 19 and 20a where the upper part of the visual field is represented. A direct, predominantly contralateral projection with a weak ipsilateral component from NPO to the nucleus of Edinger-Westphal, and an interhemispheric connection between the NPOs could be demonstrated. With respect to the anatomical connections as described in this study, no differences between normal and innate microstrabismic cats could be found. The results are discussed with respect to the binocular summation of the pupillary light reflex and its reduction in subjects with impaired binocular vision.

The pupillary light reflex in normal and innate microstrabismic cats, I: Behavior and receptive-field analysis in the nucleus praetectalis olivaris

Neurons in the nucleus praetectalis olivaris (NPO) were antidromically identified by electrical stimulation of the nucleus of Edinger-Westphal (EW), the location of preganglionic pupilloconstrictor motoneurons. Electrical stimulation within the NPO leads to bilateral pupil constriction. Single neurons recorded in the NPO respond tonically to light stimuli, and their discharge frequency increases linearly with logarithmic increase in light intensity. This characteristic identifies NPO neurons as luminance detectors. They have large receptive fields mostly lying in the upper and contralateral quadrant of the visual field. Cats with impaired binocular vision show a significantly reduced binocular summation of the pupillary light reflex (BSP), i.e. the increase of pupil constriction during binocular illumination when compared to monocular illumination is less than in normal animals. The investigation of ocular dominance and subthreshold binocular interactions in the NPO of normal and innate microstrabismic cats revealed two possible mechanisms for BSP and its reduction in strabismic subjects. First, the percentage of neurons increasing their discharge rate by illuminating either eye is significantly reduced in the NPO of innate microstrabismic cats (6.6%) when compared to normal cats (22% of all neurons tested). Second, in most NPO neurons of normal cats the subthreshold influence of the ipsilateral eye leads to an increase in neuronal activity during binocular stimulation when compared to monocular stimulation of the contralateral eye (binocular summation). The subthreshold influence of the ipsilateral eye in most NPO neurons of microstrabismic cats, however, is inhibitory, i.e. the neuronal discharge rate during binocular stimulation is decreased when compared to monocular stimulation of the contralateral eye (binocular inhibition). However, there is no significant correlation between BSP and binocularity in the NPO in individual animals. This suggests that BSP may be additionally influenced by visual structures other than NPO.

Contribution of Cholinergic and GABAergic Mechanisms to Direction Tuning, Discriminability, Response Reliability, and Neuronal Rate Correlations in Macaque Middle Temporal Area

Previous studies have investigated the effects of acetylcholine (ACh) on neuronal tuning, coding, and attention in primary visual cortex, but its contribution to coding in extrastriate cortex is unexplored. Here we investigate the effects of ACh on tuning properties of macaque middle temporal area MT neurons and contrast them with effects of gabazine, a GABAA receptor blocker. ACh increased neuronal activity, it had no effect on tuning width, but it significantly increased the direction discriminability of a neuron. Gabazine equally increased neuronal activity, but it widened tuning curves and decreased the direction discriminability of a neuron. Although gabazine significantly reduced response reliability, ACh application had little effect on response reliability. Finally, gabazine increased noise correlation of simultaneously recorded neurons, whereas ACh reduced it. Thus, both drugs increased firing rates, but only ACh application improved neuronal tuning and coding in line with effects seen in studies in which attention was selectively manipulated.

Decision-related activity in the macaque dorsal visual pathway

Brain areas at higher levels of cortical organization are thought to be more involved in decision processes than are earlier, i.e. lower, sensory areas. Hence, neuronal activity correlated with decisions should vary with an areas position in the cortical hierarchy. To test this proposal, we investigated whether a change in neuronal activity during error trials depends in a systematic way on cortical hierarchical position. While macaque monkeys discriminated the direction of moving visual stimuli, the activity of direction‐selective neurons was recorded in four extrastriate visual areas: V3A, the middle temporal area, the middle superior temporal area and the posterior part of the superior temporal polysensory area. Neuronal activity was significantly reduced in all areas when the monkeys made errors in judging the direction of stimuli moving in the preferred direction with low and intermediate luminance contrast. The amount of activity reduction was ≈ 50% in all of the visual areas. Thus, the activity on error trials is reduced in early visual processing, independent of the hierarchy in the dorsal visual pathway. The activity reduction depended on stimulus contrast and the direction of the decision relative to the stimulus motion. It was profound and significant in all areas at low stimulus contrast. However, it was nonsignificant at high stimulus contrast. Our data suggest that activity reduction on error trials is due to lack of attention in association with stimulus expectation.

Optokinetic Deficits in Albino Ferrets (Mustela putorius furo): A Behavioral and Electrophysiological Study

We compared the horizontal optokinetic reaction (OKR) and response properties of retinal slip neurons in the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) of albino and wild-type ferrets (Mustela putorius furo). In contrast to pigmented ferrets, we were unable to observe OKR in albino ferrets during binocular and monocular viewing using random dot full field stimulation and electro-oculography (EOG). Observations during early postnatal life indicate that regular OKR is present in pigmented pups 3 d after eye opening but is absent at any stage during development in albino ferrets. Unilateral muscimol injections to inactivate all neurons in the NOT-DTN containing GABAA and GABAC receptors caused spontaneous horizontal nystagmus with slow phases away from the injected hemisphere in albino as well as in pigmented animals. Retinal slip neurons in the NOT-DTN of albino ferrets identified by antidromic activation from the inferior olive and orthodromic activation from the optic chiasm were well responding to intermittent bright light stimuli, but many showed a profound reduction of responsiveness to moving stimuli. The movement-sensitive neurons exhibited no clear direction selectivity for ipsiversive stimulus movement, a characteristic property of these neurons in pigmented ferrets and other mammals. Thus, the defect rendering albino ferrets optokinetically nonresponsive is located in the visual pathway subserving the OKR, namely in or before the NOT-DTN, and not in oculomotor centers.

Retinal ganglion cells projecting to the nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system in macaque monkeys

Using classical neuroanatomical retrograde tracing methods we investigated the retinal ganglion cells projecting to the nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT‐DTN) in macaque monkeys. Our main aim was to quantify the strength of the projection from the ipsilateral retina to the NOT‐DTN. We therefore examined the number, distribution, and soma size of retinal ganglion cells involved in this projection. Electrophysiologically controlled small injections into the NOT‐DTN revealed a clearly bilateral retinal projection originating mainly from the central retina but also involving peripheral retinal regions. Labelled cells were found nasally in the contralateral retina and temporally in the ipsilateral retina with some overlap in the fovea. The projection from the ipsilateral retina was 36–43% of that from the contralateral retina. On average, only 1–6% of the local population of ganglion cells projected to the NOT‐DTN. Small soma size and large dendritic fields imply that in monkey rarely encountered, ‘specialized’ ganglion cells provide the direct retinal input to the accessory optic system (AOS). These results are discussed with respect to the symmetry of monocular horizontal optokinetic nystagmus (OKN) in primates.