Thomas FitzGibbon

RETINOTOPY OF THE HUMAN RETINAL NERVE FIBRE LAYER AND OPTIC NERVE HEAD

The organisation of the primate nerve fibre layer and optic nerve head with respect to eccentricity or the positioning of central and peripheral axons remains controversial. Crystals of the carbocyanine dyes DiI (1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindocarbocyanine perchlorate), or DiA (4‐[4‐didecylaminostryryl]‐N‐methylpridiniumiodide) were used to trace retinae ganglion cell axons within the nerve fibre layer, optic nerve head, and optic nerve. The present study demonstrated that peripheral retinal axons were scattered throughout the vitreal‐scleral depth of the nerve fibre layer. This scattered distribution was maintained as the fibres passed through the optic nerve head and into the optic nerve. Axons of the arcuate bundles showed a bias towards the scleral portions of the nerve fibre layer and a variable degree of fibre scatter across the nerve fibre layer which was not as evident in labelling from other retinal regions. There was a rough topographic representation within the optic nerve head according to retinal circumference such that both peripheral and central fibres were mixed within a wedge extending from the periphery to the centre of the nerve. Foveal fibres occupied a large proportion of the temporal aspect of the optic nerve head and nerve, whereas fibres from areas temporal to the fovea appeared to be displaced to more superior and inferior regions. Consistent with the scleral bias seen in the retina, arcuate fibres maintained a peripheral position as they passed through the optic nerve head and occupied a more peripheral position in the nerve. The present results suggest that any degree of order present within the optic nerve is not an active process; optic axons are not instructed to establish a retinotopic order within the initial portions of the visual pathway.

'Simplification' of responses of complex cells in cat striate cortex: suppressive surrounds and 'feedback' inactivation.

In mammalian striate cortex (V1), two distinct functional classes of neurones, the so‐called simple and complex cells, are routinely distinguished. They can be quantitatively differentiated from each other on the basis of the ratio between the phase‐variant (F1) component and the mean firing rate (F0) of spike responses to luminance‐modulated sinusoidal gratings (simple, F1/F0 > 1; complex, F1/F0 < 1). We investigated how recurrent cortico‐cortical connections affect the spatial phase‐variance of responses of V1 cells in the cat. F1/F0 ratios of the responses to optimally oriented drifting sine‐wave gratings covering the classical receptive field (CRF) of single V1 cells were compared to those of: (1) responses to gratings covering the CRFs combined with gratings of different orientations presented to the ‘silent’ surrounds; and (2) responses to CRF stimulation during reversible inactivation of postero‐temporal visual (PTV) cortex. For complex cells, the relative strength of the silent surround suppression on CRF‐driven responses was positively correlated with the extent of increases in F1/F0 ratios. Inactivation of PTV cortex increased F1/F0 ratios of CRF‐driven responses of complex cells only. Overall, activation of suppressive surrounds or inactivation of PTV ‘converted’ substantial proportions (50 and 30%, respectively) of complex cells into simple‐like cells (F1/F0 > 1). Thus, the simple–complex distinction depends, at least partly, on information coming from the silent surrounds and/or feedback from ‘higher‐order’ cortices. These results support the idea that simple and complex cells belong to the same basic cortical circuit and the spatial phase‐variance of their responses depends on the relative strength of different synaptic inputs.

Geniculocortical relay of blue-off signals in the primate visual system

A fundamental dichotomy in the subcortical visual system exists between on- and off-type neurons, which respectively signal increases and decreases of light intensity in the visual environment. In primates, signals for red-green color vision are carried by both on- and off-type neurons in the parvocellular division of the subcortical pathway. It is thought that on-type signals for blue-yellow color vision are carried by cells in a distinct, diffusely projecting (koniocellular) pathway, but the pathway taken by blue-off signals is not known. Here, we measured blue-off responses in the subcortical visual pathway of marmoset monkeys. We found that the cells exhibiting blue-off responses are largely segregated to the koniocellular pathway. The blue-off cells show relatively large receptive fields, sluggish responses to maintained contrast, little sign of an inhibitory receptive-field surround mechanism, and negligible functional input from an intrinsic (melanopsin-based) phototransductive mechanism. These properties are consistent with input from koniocellular or “W-like” ganglion cells in the retina and suggest that blue-off cells, as previously shown for blue-on cells, could contribute to cortical mechanisms for visual perception via the koniocellular pathway.

Retinogeniculate transmission by NMDA and non-NMDA receptors in the cat

The contributions of N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino acid (EAA) receptors to retinogeniculate transmission were investigated in the cat. The EAA antagonists 2-amino-5-phosphonovaleric acid (APV) and kynurenic acid (KYN) were used to block the NMDA receptors and all EAA receptors, respectively. Antagonistic effects on the visual response were assessed with single On/Off stimuli of 2 s duration or repetitive flicker stimulation (5 Hz) with a light spot projected onto the receptive field center. With APV, the NMDA response could be almost completely abolished but the visual response to repetitive stimulation was reduced on average by only 34%. Initial (transient) components of the single flash response were attenuated on average by 23%, the residual (sustained) component by 48%. With KYN the responses to NMDA, quisqualate (QUIS) and glutamate (GLU) were abolished or strongly reduced as was the visual response to flicker (mean 58%) and single flash stimulation (mean transient 73%, sustained 90%). Prolonged iontophoretic applications of the agonists GLU, QUIS and NMDA revealed receptor desensitization or competitive interactions with the naturally released transmitter in a dose-dependent manner. When the responses to any of the 3 agonists declined during continuous application, superimposed visual responses were clearly reduced in amplitude. Visual response amplitudes were also reduced when superimposed on steady state QUIS responses but unchanged in amplitude when superimposed on steady state NMDA responses. In conclusion, non-NMDA as well as NMDA receptors seem to participate in cat retinogeniculate transmission. Non-NMDA receptors appear to be most important for the initial component but can also maintain the visual response, while the NMDA receptors seem to be more effective during the later component of the response.

The human fetal retinal nerve fiber layer and optic nerve head: A DiI and DiA tracing study

The organization of the primate nerve fiber layer and optic nerve head with respect to the positioning of central and peripheral axons remains controversial. Data were obtained from 32 human fetal retinae aged between 15 and 21 weeks of gestation. Crystals of the carbocyanine dyes, DiI or DiA, and fluorescence microscopy were used to identify axonal populations from peripheral retinal ganglion cells. Peripheral ganglion cell axons were scattered throughout the vitreal-scleral depth of the nerve fiber layer. Such a scattered distribution was maintained as the fibers passed through the optic nerve head and along the optic nerve. There was a rough topographic representation within the optic nerve head according to retinal quadrant such that both peripheral and central fibers were mixed within a wedge extending from the periphery to the center of the nerve. There was no indication that the fibers were reorganized in any way as they passed through the optic disc and into the nerve. The present results suggest that any degree of order present within the fiber layer and optic nerve is not an active process but a passive consequence of combining the fascicles of the retinal nerve fiber layer. Optic axons are not instructed to establish a retinotopic order and the effect of guidance cues in reordering fibers, particularly evident prechiasmatically and postchiasmatically, does not appear to be present within the nerve fiber layer or optic nerve head in humans.

Soma and axon diameter distributions and central projections of ferret retinal ganglion cells

Using a combination of retrograde horseradish peroxidase (HRP) labelling, silver staining, and electron microscopy, we have assessed the relationship between retinal ganglion cell soma size and axon diameter in the adult ferret (Mustela putorius furo). Retinal ganglion cells were labelled following injections of HRP into the lateral geniculate nucleus (LGN), superior colliculus (SC), or LGN+SC. The soma size distributions following LGN, SC, or LGN+SC injections were all unimodal showing considerable overlap between different cell classes. This was confirmed for alpha cells identified on the basis of dendritic filling or from neurofibrillar-stained retinae. Analysis of the soma size and axon diameters of a population of heavily labelled retinal ganglion cells showed a significant correlation between the two. However, the overall distribution of intraretinal axon diameter was bimodal with an extended tail. Analysis of the ganglion cell distributions in the adult ferret indicates that beta cells comprise about 50.5-55%, gamma 42.5-47%, and alpha 2.5% of the ganglion cell population. This implies that the proportion of gamma, beta, alpha cells in both cat and ferret retina is highly conserved despite differences in visual specialization in the two species.

Anatomical correlations between soma size, axon diameter, and intraretinal length for the alpha ganglion cells of the cat retina

Retinal ganglion cells within the same region of the retina may have different lengths of axon before reaching the optic disc depending on the route they take with respect to the temporal raphe. We have investigated whether there is a correlation between soma and intraretinal axon diameter and how these parameters relate to intraretinal axon length on both sides of the cat temporal raphe. Retinas were wholemounted and alpha-cell somata and fibers stained with a modified neurofibrillar method. Moving peripherally from the area centralis along the raphe there was a progressively increasing difference between the intraretinal axon lengths for nearly adjacent cells across the raphe, which reached a maximum of 4-5 mm at the retinal periphery. Cells on the nasal aspect of the raphe had shorter axons than did adjacent cells on the temporal aspect of the raphe. Comparison of soma diameter samples across the raphe showed there was no clear trend between soma diameter and intraretinal length. Replotting the raphe and sample areas on a cell density map indicated that differences in soma diameter could be attributed to ganglion-cell density differences between the sampled areas. Examination of the stained cells revealed that within the initial length of the axon there was a region showing a reduction of axon diameter (diameter less than 1 micron), which varied in length from cell to cell. The axon was, therefore, divided into three segments: the portion of axon prior to thinning (A), the thin segment itself (B), and the part of the axon after the thin segment (C). The diameter of each segment (A,B,C) and the lengths of the first and second segments (A,B) were significantly correlated with soma diameter (P less than 0.001). From measurements of the axon diameter of segment C, it was concluded that alpha-cell axons continue to increase in diameter along their path towards the optic disc. The present report indicates that alpha-cell soma size, when going from the area centralis to the periphery along the raphe, reaches a plateau and then declines within more peripheral retinal locations in spite of increasing intraretinal axon length. Thus, there is no positive correlation between soma or axon diameter and intraretinal axon length. The anatomical findings are discussed in relation to previous reports of retinal development and complementary conduction times within intraretinal and extraretinal visual pathways.

Rostral reticular nucleus of the thalamus sends a patchy projection to the pulvinar lateralis-posterior complex of the cat

The pulvinar lateralis posterior complex (Pul-LP) and the reticular nucleus of the thalamus (RE) are thought to be involved in visual and attention-related tasks. This report provides data on the anatomical connections between these two nuclei following the analysis of injections of horseradish peroxidase (HRP) + [3H]leucine into the Pul-LP and RE of the cat. Following the retrograde transport of HRP from the Pul-LP, labeled cells were distributed in regions of the RE ventral to the caudate nucleus and adjacent to the stria terminalis between Horsley-Clarke anterior-posterior (AP) coordinates 13.0 and 9.5 and more caudally in areas dorsal and ventral to the lateral geniculate nucleus (LGN) between AP 9.0 and 4.5. The majority of the cell labeling within the RE following injections within the Pul-LP was seen dorsal to the lateral geniculate nucleus around AP 6.5-6.0. Cell labeling was heaviest following injections within the lateral LP in contrast to injections within the Pul which resulted in fewer labeled cells. Autoradiographic analysis of the anterograde transport of leucine showed that the labeled Pul-LP fibers within the RE did not completely coincide with the distribution of HRP-labeled reticular cells from the same injection site. This indicated a lack of strict reciprocity between these two nuclei. In addition, injections of [3H]leucine into dorsomedial areas of the RE near the rostral pole of the LGN resulted in a patchy distribution of label within the Pul-LP which was most prominent as oblique dorsoventral slabs across the thalamus. It was inferred that this distribution was along the borders between different subdivisions within the Pul-LP. The lack of strict reciprocity between the thalamic relay nuclei and the reticular nucleus implies that areas of the Pul-LP may receive inhibition from RE regions which they do not directly influence; this anatomical feature may provide a basis for selective inhibition of thalamic nuclei.

Projections from striate and extrastriate visual cortices of the cat to the reticular thalamic nucleus

We have studied the pattern of connectivity of the visual cortical areas 17, 18, 19, 20a, 21a, posteromedial lateral (PMLS), and the posterolateral lateral (PLLS) suprasylvian areas with the reticular thalamic nucleus (RTN) of the cat ventral thalamus. Three cortical areas per hemisphere were injected iontophoretically with either 4% wheat germ agglutinin‐horseradish peroxidase, 4% dextran‐fluororuby, or 4% dextran‐biotin. The visual field representations of the injection sites were determined by reference to previously published visuotopic maps of the cortex. The locations of labelled fibres, presumed terminals and cell bodies were determined with the aid of a camera lucida attachment and computer aided stereometry. In the ventral thalamus, the primary visual cortices (areas 17 and 18) project in a topographic manner to both the perigeniculate nucleus (PGN) and the RTN. By contrast, the “higher” visual cortical areas (areas 19, 21a, 20a, PMLS, and PLLS) project only to the RTN. Our experiments demonstrate the existence of a single, albeit coarse, visuotopic map within the RTN but do not support the notion of separate subregions within the RTN that can be related specifically to a particular visual cortical area. The putative single visuotopic map in the RTN appears to be organised in such a way that the vertical meridians are represented along the rostrocaudal axis of the RTN, whereas the horizontal meridians are mapped within the dorsoventral axis of the nucleus. The upper visual field is represented within regions of the RTN adjacent to the caudal part of the dorsal lateral geniculate nucleus (LGNd), whereas the lower visual field is represented in the parts of the RTN rostral to the LGNd. The map also shows a ventrodorsal shift along the rostrocaudal axis of the RTN such that in the rostral RTN the representation of vertical meridian is placed more ventrally than that in the caudal part of the nucleus. J. Comp. Neurol. 410:467–488, 1999.

Retinal ganglion cell axon diameter spectrum of the cat: mean axon diameter varies according to retinal position

Axon diameters of retinal ganglion cells were measured from electron micrographs of the nerve fiber layer of the cat. Three adult retinae were examined which had mean axonal diameters of 1.18 +/- 0.86 (n = 5553), 1.12 +/- 0.79 (n = 7265), and 1.47 +/- 1.11 microns (n = 10,867). Cumulative histograms from several locations adjacent to the optic disc were unimodal (modal peaks: 0.6-0.8 microns). This unimodal distribution, however, did not reflect the regional differences in axonal diameters found throughout the retina. In many locations, especially those related to axons of the temporal retina, axon diameter distributions were clearly bimodal or even trimodal (modal peaks: 0.6-0.8, 1.4-2.1, and 3.3 microns). Measurements from one retina indicated that the mean diameters of axons arising from the area centralis and visual streak (0.94 +/- 0.63 and 0.98 +/- 0.68, respectively) were not significantly different from each other; however, when compared to other areas around the optic disc, the percentage of fibers with diameters between 1.5-2.0 microns was highest in the sample adjacent to the area centralis. Axons temporal to the optic disc were found to be on average larger than those nasal to the optic disc; similarly superior axons were larger than inferior axons. Axonal distributions at the retinal periphery were found to be significantly different from those at the optic disc (P < or = 0.05) and contained a higher percentage of medium-sized axons and fewer small axons. In each of the three retinae the proportions small, medium, and large axons were respectively gamma: 46; 47; 48, beta: 50; 49; 48, and alpha: 4; 4; 4; regional differences in the proportions of each axonal class are compared to previously published ganglion cell density maps. Differences between axonal bundles within each sample location were not significantly different; however, in one retina axons in the scleral half of the fiber layer were significantly larger (P < or = 0.01) than axons in the vitreal half of the nerve fiber layer adjacent to the optic disc. When compared to the axonal diameter distributions found within the optic nerve (Cottee et al., 1991) and optic tract (Reese et al., 1991), our data indicates that the diameter of retinal axons may increase by up to 30% along the length of the visual pathway.